The influence of needleless connectors and inserted catheters on flow rates through vascular introducer sheaths.

SummaryA vascular introducer sheath is often used for rapid volume replacement. However, common manipulations such as the addition of needleless connectors to infusion ports and the insertion of catheters or other devices through the introducer sheath may impede flow. In this study we utilised a rapid infuser to deliver room-temperature normal saline through two introducer sheath configurations with and without the addition of needleless connectors and the placement of catheters through the introducer sheaths. The maximal flow rate delivered by the rapid infuser was 1000 mL/min, which was observed with both introducer sheath sizes tested without additional resistive elements. However, with the addition of a needleless connector, flow rates through the introducer sheaths were substantially lower (64 (standard deviation (SD) 6) mL/min and 61 (SD 7) mL/min for the 8.5 Fr and 9 Fr introducers, respectively). Flow rates were also reduced when catheters were placed within the sheaths (298 (SD 9) mL/min with the 7 Fr catheter and 74 (SD 9) mL/min with the 8 Fr catheter placed in an 8.5 Fr sheath; 649 (SD 6) mL/min with the 7 Fr catheter and 356 (SD 14) mL/min with the 8 Fr catheter placed in the 9 Fr sheath). These findings indicated that both needleless connectors and the placement of catheters through vascular introducer sheaths substantially reduced potential flow rates. Even 'large' vascular introducer sheaths capable of delivering high flow rates could be rendered minimally effective for rapid fluid administration when used in this way. Clinicians should consider these impediments to flow when rapid fluid administration is required, and obtain alternative vascular access if necessary.

Beekeeping in Europe facing climate change: A mixed methods study on perceived impacts and the need to adapt according to stakeholders and beekeepers.

The beekeeping sector is suffering from the detrimental effects of climate change, both directly and indirectly. Despite numerous studies conducted on this subject, large-scale research incorporating stakeholders' and beekeepers' perspectives has remained elusive. This study aims to bridge this gap by assessing the extent to which stakeholders involved in the European beekeeping sector and European beekeepers perceive and experience the impacts of climate change on their operations, and whether they had to adapt their practices accordingly. To this end, a mixed-methods study including in-depth stakeholder interviews (n = 41) and a pan-European beekeeper survey (n = 844) was completed within the frame of the EU-funded H2020-project B-GOOD. The development of the beekeeper survey was informed by insights from literature and the stakeholder interviews. The results highlighted significant regional disparities in the perceived impacts of climate change, with beekeepers in Southern European regions expressing more negative outlooks, while Northern European beekeepers reported more favourable experiences. Furthermore, survey analysis revealed beekeepers who were classified as 'heavily impacted' by climate change. These beekeepers reported lower average honey yields, higher colony winter loss rates and a stronger perceived contribution of honey bees to pollination and biodiversity, underscoring climate change's detrimental impacts on the beekeeping sector. Multinomial logistic regression revealed determinants of the likelihood of beekeepers being classified as 'heavily impacted' by climate change. This analysis indicates that Southern European beekeepers experienced a 10-fold likelihood of being classified as heavily impacted by climate change compared to Northern European beekeepers. Other significant factors distinguishing 'winners' and 'losers' were self-reported level of professionalism as a beekeeper (ranging from pure hobbyist to fully professional, Odds Ratio (OR) = 1.31), number of years active in beekeeping (OR = 1.02), availability of floral resources throughout the bee season (OR = 0.78), beehives located in a forested environment (OR = 1.34), and the presence of local policy measures addressing climate change-related challenges (OR = 0.76).

Minimizing habitat conflicts in meeting net-zero energy targets in the western United States.

The scale and pace of energy infrastructure development required to achieve net-zero greenhouse gas (GHG) emissions are unprecedented, yet our understanding of how to minimize its potential impacts on land and ocean use and natural resources is inadequate. Using high-resolution energy and land-use modeling, we developed spatially explicit scenarios for reaching an economy-wide net-zero GHG target in the western United States by 2050. We found that among net-zero policy cases that vary the rate of transportation and building electrification and use of fossil fuels, nuclear generation, and biomass, the "High Electrification" case, which utilizes electricity generation the most efficiently, had the lowest total land and ocean area requirements (84,000 to 105,000 km2 vs. 88,100 to 158,000 km2 across all other cases). Different levels of land and ocean use protections were applied to determine their effect on siting, environmental and social impacts, and energy costs. Meeting the net-zero target with stronger land and ocean use protections did not significantly alter the share of different energy generation technologies and only increased system costs by 3%, but decreased additional interstate transmission capacity by 20%. Yet, failure to avoid development in areas with high conservation value is likely to result in substantial habitat loss.

Material Needs of Emergency Department Patients: A Systematic Review.

BACKGROUND: Interest in social determinants of health (SDOH) has expanded in recent years, driven by a recognition that such factors may influence health outcomes, services use, and health care costs. One subset of SDOH is material needs such as housing and food. We conducted a systematic review of the literature on material needs among emergency department (ED) patients in the United States. METHODS: We followed PRISMA guidelines for systematic review methodology. With the assistance of a research librarian, four databases were searched for studies examining material needs among ED patients. Two reviewers independently screened titles, abstracts, and full text to identify eligible articles. Information was abstracted systematically from eligible articles. RESULTS: Forty-three articles were eligible for inclusion. There was heterogeneity in study methods; single-center, cross-sectional studies were most common. Specific material needs examined included homelessness, poverty, housing insecurity, housing quality, food insecurity, unemployment, difficulty paying for health care, and difficulty affording basic expenses. Studies overwhelmingly supported the notion that ED patients have a high prevalence of a number of material needs. CONCLUSIONS: Despite some limitations in the individual studies examined in this review, the plurality of prior research confirms that the ED serves a vulnerable population with high rates of material needs. Future research is needed to better understand the role these needs play for ED patients and how to best address them.

Acceptability of smartphone text- and voice-based ecological momentary assessment (EMA) methods among low income housing residents in New York City.

OBJECTIVES: This study aimed to evaluate the acceptability of smartphone-based text message- and voice-based ecological momentary assessment (EMA) methods among a sample of low-income housing residents in New York City. Using data from the community-based NYC Low Income Housing, Neighborhoods and Health Study (n = 112), the acceptability of text message- and voice-based EMA methods were assessed via survey. RESULTS: Overall, 88.4% of participants reported that they would participate in a study that utilized text message-based EMA. These analyses showed no appreciable differences by sub-groups (p > .05). Overall, 80.2% of participants reported that they would participate in a study that used voice-based EMA. This voice-based method was least acceptable among participants younger than 25 years old compared to participants of all other ages, χ2(2) = 10.107, p = .006 (among the younger participants 60.7% reported "yes" regarding the anticipated acceptability of voice-based EMA and 39.3% reported "no"). Overall, this work suggests that text message- and voice-based EMA methods are acceptable for use among low-income housing residents. However, the association between age and the acceptability of voice-based EMA suggests that these methods may be less suited for younger populations.

Perioperative Management of Adult Patients With External Ventricular and Lumbar Drains: Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care.

External ventricular drains and lumbar drains are commonly used to divert cerebrospinal fluid and to measure cerebrospinal fluid pressure. Although commonly encountered in the perioperative setting and critical for the care of neurosurgical patients, there are no guidelines regarding their management in the perioperative period. To address this gap in the literature, The Society for Neuroscience in Anesthesiology & Critical Care tasked an expert group to generate evidence-based guidelines. The document generated targets clinicians involved in perioperative care of patients with indwelling external ventricular and lumbar drains.

Perceived spatial stigma, body mass index and blood pressure: a global positioning system study among low-income housing residents in New York City.

Previous research has highlighted the salience of spatial stigma on the lives of low-income residents, but has been theoretical in nature and/or has predominantly utilised qualitative methods with limited generalisability and ability to draw associations between spatial stigma and measured cardiovascular health outcomes. The primary objective of this study was to evaluate relationships between perceived spatial stigma, body mass index (BMI), and blood pressure among a sample of low-income housing residents in New York City (NYC). Data come from the community-based NYC Low-income Housing, Neighborhoods and Health Study. We completed a crosssectional analysis with survey data, which included the four items on spatial stigma, as well objectively measured BMI and blood pressure data (analytic n=116; 96.7% of the total sample). Global positioning systems (GPS) tracking of the sample was conducted for a week. In multivariable models (controlling for individual-level age, gender, race/ethnicity, education level, employment status, total household income, neighborhood percent non-Hispanic Black and neighborhood median household income) we found that participants who reported living in an area with a bad neighborhood reputation had higher BMI (B=4.2, 95%CI: -0.01, 8.3, P=0.051), as well as higher systolic blood pressure (B=13.2, 95%CI: 3.2, 23.1, P=0.01) and diastolic blood pressure (B=8.5, 95%CI: 2.8, 14.3, P=0.004). In addition, participants who reported living in an area with a bad neighborhood reputation had increased risk of obesity/overweight [relative risk (RR)=1.32, 95%CI: 1.1, 1.4, P=0.02) and hypertension/pre-hypertension (RR=1.66, 95%CI: 1.2, 2.4, P=0.007). However, we found no differences in spatial mobility (based GPS data) among participants who reported living in neighborhoods with and without spatial stigma (P>0.05). Further research is needed to investigate how placebased stigma may be associated with impaired cardiovascular health among individuals in stigmatised neighborhoods to inform effective cardiovascular risk reduction interventions.

Local spatial clustering in youths' use of tobacco, alcohol, and marijuana in Boston.

BACKGROUND: Understanding geographic variation in youth drug use is important for both identifying etiologic factors and planning prevention interventions. However, little research has examined spatial clustering of drug use among youths by using rigorous statistical methods. OBJECTIVES: The purpose of this study was to examine spatial clustering of youth use of tobacco, alcohol, and marijuana. METHODS: Responses on tobacco, alcohol, and marijuana use from 1,292 high school students ages 13-19 who provided complete residential addresses were drawn from the 2008 Boston Youth Survey Geospatial Dataset. Response options on past month use included "none," "1-2," "3-9," and "10 or more." The response rate for each substance was approximately 94%. Spatial clustering of youth drug use was assessed using the spatial Bernoulli model in the SatScan™ software package. RESULTS: Approximately 12%, 36%, and 18% of youth reported any past-month use of tobacco, alcohol, and/or marijuana, respectively. Two clusters of elevated past tobacco use among Boston youths were generated, one of which was statistically significant. This cluster, located in the South Boston neighborhood, had a relative risk of 5.37 with a p-value of 0.00014. There was no significant localized spatial clustering in youth past alcohol or marijuana use in either the unadjusted or adjusted models. CONCLUSION: Significant spatial clustering in youth tobacco use was found. Finding a significant cluster in the South Boston neighborhood provides reason for further investigation into neighborhood characteristics that may shape adolescents' substance use behaviors. This type of research can be used to evaluate the underlying reasons behind spatial clustering of youth substance and to target local drug abuse prevention interventions and use.

Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas.

During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers.

Functional interaction between angiotensin II receptor type 1 and chemokine (C-C motif) receptor 2 with implications for chronic kidney disease.

Understanding functional interactions between G protein-coupled receptors is of great physiological and pathophysiological importance. Heteromerization provides one important potential mechanism for such interaction between different signalling pathways via macromolecular complex formation. Previous studies suggested a functional interplay between angiotensin II receptor type 1 (AT1) and Chemokine (C-C motif) Receptor 2 (CCR2). However the molecular mechanisms are not understood. We investigated AT1-CCR2 functional interaction in vitro using bioluminescence resonance energy transfer in HEK293 cells and in vivo using subtotal-nephrectomized rats as a well-established model for chronic kidney disease. Our data revealed functional heteromers of these receptors resulting in CCR2-Gαi1 coupling being sensitive to AT1 activation, as well as apparent enhanced ß-arrestin2 recruitment with agonist co-stimulation that is synergistically reversed by combined antagonist treatment. Moreover, we present in vivo findings where combined treatment with AT1- and CCR2-selective inhibitors was synergistically beneficial in terms of decreasing proteinuria, reducing podocyte loss and preventing renal injury independent of blood pressure in the subtotal-nephrectomized rat model. Our findings further support a role for G protein-coupled receptor functional heteromerization in pathophysiology and provide insights into previous observations indicating the importance of AT1-CCR2 functional interaction in inflammation, renal and hypertensive disorders.

Congenital atresia of the inferior vena cava and antithrombin III deficiency in a young adult: compounding risk factors for deep vein thrombosis.

Atresia, or absence, of the inferior vena cava (AIVC) is a rare, usually fortuitous finding on advanced imaging that predisposes patients to deep venous thrombosis (DVT). In young adults who lack predisposing risk factors but nonetheless develop extensive or bilateral DVTs, AIVC should be considered. We describe a case of a previously healthy 17-year-old male patient who developed an extensive renal vein thrombus due to the absence of the superior portion of his IVC compounded with previously undiagnosed antithrombin III deficiency. We discuss the diagnosis and management of this complicated condition.

Incorporating land-use requirements and environmental constraints in low-carbon electricity planning for California.

The land-use implications of deep decarbonization of the electricity sector (e.g., 80% below 1990 emissions) have not been well-characterized quantitatively or spatially. We assessed the operational-phase land-use requirements of different low-carbon scenarios for California in 2050 and found that most scenarios have comparable direct land footprints. While the per MWh footprint of renewable energy (RE) generation is initially higher, that of fossil and nuclear generation increases over time with continued fuel use. We built a spatially explicit model to understand the interactions between resource quality and environmental constraints in a high RE scenario (>70% of total generation). We found that there is sufficient land within California to meet the solar and geothermal targets, but areas with the highest quality wind and solar resources also tend to be those with high conservation value. Development of some land with lower conservation value results in lower average capacity factors, but also provides opportunity for colocation of different generation technologies, which could significantly improve land-use efficiency and reduce permitting, leasing, and transmission infrastructure costs. Basing siting decisions on environmentally-constrained long-term RE build-out requirements produces significantly different results, including better conservation outcomes, than implied by the current piecemeal approach to planning.

Perceived neighborhood illicit drug selling, peer illicit drug disapproval and illicit drug use among U.S. high school seniors.

BACKGROUND: This study examined associations between perceived neighborhood illicit drug selling, peer illicit drug disapproval and illicit drug use among a large nationally representative sample of U.S. high school seniors. METHODS: Data come from Monitoring the Future (2007-2011), an annual cross-sectional survey of U.S. high school seniors. Students reported neighborhood illicit drug selling, friend drug disapproval towards marijuana and cocaine use, and past 12-month and past 30-day illicit drug use (N = 10,050). Multinomial logistic regression models were fit to explain use of 1) just marijuana, 2) one illicit drug other than marijuana, and 3) more than one illicit drug other than marijuana, compared to "no use". RESULTS: Report of neighborhood illicit drug selling was associated with lower friend disapproval of marijuana and cocaine; e.g., those who reported seeing neighborhood sales "almost every day" were less likely to report their friends strongly disapproved of marijuana (adjusted odds ratio [AOR] = 0.38, 95% CI: 0.29, 0.49) compared to those who reported never seeing neighborhood drug selling and reported no disapproval. Perception of neighborhood illicit drug selling was also associated with past-year drug use and past-month drug use; e.g., those who reported seeing neighborhood sales "almost every day" were more likely to report 30-day use of more than one illicit drug (AOR = 11.11, 95% CI: 7.47, 16.52) compared to those who reported never seeing neighborhood drug selling and reported no 30-day use of illicit drugs. CONCLUSIONS: Perceived neighborhood drug selling was associated with lower peer disapproval and more illicit drug use among a population-based nationally representative sample of U.S. high school seniors. Policy interventions to reduce "open" (visible) neighborhood drug selling (e.g., problem-oriented policing and modifications to the physical environment such as installing and monitoring surveillance cameras) may reduce illicit drug use and peer disapproval of illicit drugs.

Projected supply of and demand for oncologists and radiation oncologists through 2025: an aging, better-insured population will result in shortage.

PURPOSE: The American Society of Clinical Oncology (ASCO) published a study in 2007 that anticipated a shortage of oncologists by 2020. This study aims to update and better assess the market for chemotherapy and radiation therapy and the impact of health reform on capacity of and demand for oncologists and radiation oncologists. METHODS: The supply of oncologists and radiation oncologists, by age, sex, and specialty, was projected through 2025 with an input-output model. The Medical Expenditure Panel Survey, commercial claims, and Medicare claims were analyzed to determine patterns of use by patient characteristics such as age, sex, health insurance coverage, cancer site, physician specialty, and service type. Patterns of use were then applied to the projected prevalence of cancer, using data from the SEER Program of the National Cancer Institute. RESULTS: Beginning in 2012, 16,347 oncologists and radiation oncologists were active and supplying 15,190 full-time equivalents (FTEs) of patient care. Without consideration of the Affordable Care Act (ACA), overall demand for oncologist services is projected to grow 40% (21,255 FTEs), whereas supply may grow only 25% (18,997 FTEs), generating a shortage of 2,258 FTEs in 2025. When fully implemented, the ACA could increase the demand for oncologists and radiation oncologists by 500,000 visits per year, increasing the shortage to 2,393 FTEs in 2025. CONCLUSION: Anticipated shortages are largely consistent with the projections of the ASCO 2007 workforce study but somewhat more delayed. The ACA may modestly exacerbate the shortage. Unless oncologist productivity can be enhanced, the anticipated shortage will strain the ability to provide quality cancer care.

Stakeholder perspectives and values when setting waterbird population targets: implications for flyway management planning in a European context.

Managing and controlling wildlife species within Europe is an acknowledged part of conservation management, yet deciding and setting a population target in order to control a population is perceived to be conceptually very challenging. We interviewed stakeholders, within a variety of governmental and non-governmental organizations, to evaluate their perspectives about setting population targets as part of waterbird management for controlling population sizes. We conclude that the setting of a quantifiable population target is beneficial as a measurable objective for monitoring and evaluating management actions. However, it must be recognised as just one possible measurable objective and there may well be multiple supporting objectives that encapsulate the management aims of different stakeholders. When considering wide-scale control of waterbirds species, where it is likely that population size matters, any population target should be coupled to the issues being addressed. We highlight that it is important to actively engage with stakeholders as part of the decision-making process, not only to gain consensus but to share knowledge. A clear understanding of the context and the rationale for controlling a waterbird species is needed to align the interests of diverse stakeholders. The provision of scientific data and the continuous monitoring of management actions is viewed as beneficial and demanded by stakeholders, as part of any decision-making process when setting population targets. This facilitates effective evaluation of management actions, helping managers make wise decisions as well as enabling the continued development of management plans.

Dietetics supply and demand: 2010-2020.

The Academy of Nutrition and Dietetics, in conjunction with the Commission on Dietetic Registration (CDR), invited The Lewin Group to undertake an analysis of the dietetics workforce. The purpose of the workforce study was to develop a model that can project the supply and demand for both registered dietitians (RDs) and dietetic technicians, registered (DTRs) (collectively referred to as CDR-credentialed dietetics practitioners) as the result of various key drivers of change. The research team was asked to quantify key market factors where possible and to project likely paths for the evolution of workforce supply and demand, as well as to assess the implications of the findings. This article drew on the survey research conducted by Readex Research and futurist organizations such as Signature i and Trend Spot Consulting. Furthermore, members of the Dietetics Workforce Demand Task Force were a source of institutional and clinical information relevant to the credentialed dietetics workforce--including their opinions and judgment of the current state of the health care market for dietetic services, its future state, and factors affecting it, which were useful and were integrated with the objective sources of data. The model is flexible and accommodates the variation in how RDs and DTRs function in diverse practice areas. For purposes of this study and model, the dietetics workforce is composed of RDs and DTRs. This report presents the results of this workforce study and the methodology used to calculate the projected dietetics workforce supply and demand. The projections are based on historical trends and estimated future changes. Key findings of the study included the following: • The average age of all CDR-credentialed dietetics practitioners in baseline supply (2010) is 44 years; approximately 96% are women. • Approximately 55% of CDR-credentialed dietetics practitioners work in clinical dietetics. • The annual growth rate of supply of CDR-credentialed dietetics practitioners declined from 3% in the early 1990s to 1.5% by 2010. • The net supply of CDR-credentialed dietetics practitioners is projected to grow by 1.1% annually. • Approximately 75% of the demand for the dietetics workforce will be met by the 2020 supply of CDR-credentialed dietetics practitioners. • The aging population, health care reform, increased prevalence of certain conditions (including obesity), and growth in the food industry are key factors affecting the demand.

The technology path to deep greenhouse gas emissions cuts by 2050: the pivotal role of electricity.

Several states and countries have adopted targets for deep reductions in greenhouse gas emissions by 2050, but there has been little physically realistic modeling of the energy and economic transformations required. We analyzed the infrastructure and technology path required to meet California's goal of an 80% reduction below 1990 levels, using detailed modeling of infrastructure stocks, resource constraints, and electricity system operability. We found that technically feasible levels of energy efficiency and decarbonized energy supply alone are not sufficient; widespread electrification of transportation and other sectors is required. Decarbonized electricity would become the dominant form of energy supply, posing challenges and opportunities for economic growth and climate policy. This transformation demands technologies that are not yet commercialized, as well as coordination of investment, technology development, and infrastructure deployment.

Closed-loop continuous infusions of etomidate and etomidate analogs in rats: a comparative study of dosing and the impact on adrenocortical function.

BACKGROUND: Etomidate is a sedative-hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. METHODS: A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague-Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1-24 and measuring serum corticosterone concentrations every 30 min. RESULTS: The sedative-hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion termination varied (methoxycarbonyl etomidate > carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. CONCLUSIONS: Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative-hypnotic maintenance agents when hemodynamic stability is desirable.

Discharge of the readily releasable pool with action potentials at hippocampal synapses.

A readily releasable pool (RRP) of synaptic vesicles has been identified at hippocampal synapses with application of hypertonic solution. RRP size correlates with important properties of synaptic function such as release probability. However, a discrepancy in RRP size has been reported depending on the method used to evoke synaptic release. This study was undertaken to determine quantitative relationships between the RRP defined with hypertonic solution and that released with trains of action potentials. We find that asynchronous release at cell culture synapses contributes significantly to the discharge of the RRP with trains of action potentials and that RRP size is the same when elicited by either nerve stimuli or hypertonic challenge.

Myeloid leukemia factor 1 associates with a novel heterogeneous nuclear ribonucleoprotein U-like molecule.

Myeloid leukemia factor 1 (MLF1) is an oncoprotein associated with hemopoietic lineage commitment and acute myeloid leukemia. Here we show that Mlf1 associated with a novel binding partner, Mlf1-associated nuclear protein (Manp), a new heterogeneous nuclear ribonucleoprotein (hnRNP) family member, related to hnRNP-U. Manp localized exclusively in the nucleus and could redirect Mlf1 from the cytoplasm into the nucleus. The nuclear content of Mlf1 was also regulated by 14-3-3 binding to a canonical 14-3-3 binding motif within the N terminus of Mlf1. Significantly Mlf1 contains a functional nuclear export signal and localized primarily to the nuclei of hemopoietic cells. Mlf1 was capable of binding DNA, and microarray analysis revealed that it affected the expression of several genes, including transcription factors. In summary, this study reveals that Mlf1 translocates between nucleus and cytoplasm, associates with a novel hnRNP, and influences gene expression.