Self-assembled MmsF proteinosomes control magnetite nanoparticle formation in vitro.

Magnetotactic bacteria synthesize highly uniform intracellular magnetite nanoparticles through the action of several key biomineralization proteins. These proteins are present in a unique lipid-bound organelle (the magnetosome) that functions as a nanosized reactor in which the particle is formed. A master regulator protein of nanoparticle formation, magnetosome membrane specific F (MmsF), was recently discovered. This predicted integral membrane protein is essential for controlling the monodispersity of the nanoparticles in Magnetospirillum magneticum strain AMB-1. Two MmsF homologs sharing over 60% sequence identity, but showing no apparent impact on particle formation, were also identified in the same organism. We have cloned, expressed, and used these three purified proteins as additives in synthetic magnetite precipitation reactions. Remarkably, these predominantly α-helical membrane spanning proteins are unusually highly stable and water-soluble because they self-assemble into spherical aggregates with an average diameter of 36 nm. The MmsF assembly appears to be responsible for a profound level of control over particle size and iron oxide (magnetite) homogeneity in chemical precipitation reactions, consistent with its indicated role in vivo. The assemblies of its two homologous proteins produce imprecise various iron oxide materials, which is a striking difference for proteins that are so similar to MmsF both in sequence and hierarchical structure. These findings show MmsF is a significant, previously undiscovered, protein additive for precision magnetite nanoparticle production. Furthermore, the self-assembly of these proteins into discrete, soluble, and functional "proteinosome" structures could lead to advances in fields ranging from membrane protein production to drug delivery applications.

Longitudinal changes in brain metabolites following pediatric concussion.

Concussion is commonly characterized by a cascade of neurometabolic changes following injury. Magnetic Resonance Spectroscopy (MRS) can be used to quantify neurometabolites non-invasively. Longitudinal changes in neurometabolites have rarely been studied in pediatric concussion, and fewer studies consider symptoms. This study examines longitudinal changes of neurometabolites in pediatric concussion and associations between neurometabolites and symptom burden. Participants who presented with concussion or orthopedic injury (OI, comparison group) were recruited. The first timepoint for MRS data collection was at a mean of 12 days post-injury (n = 545). Participants were then randomized to 3 (n = 243) or 6 (n = 215) months for MRS follow-up. Parents completed symptom questionnaires to quantify somatic and cognitive symptoms at multiple timepoints following injury. There were no significant changes in neurometabolites over time in the concussion group and neurometabolite trajectories did not differ between asymptomatic concussion, symptomatic concussion, and OI groups. Cross-sectionally, Choline was significantly lower in those with persistent somatic symptoms compared to OI controls at 3 months post-injury. Lower Choline was also significantly associated with higher somatic symptoms. Although overall neurometabolites do not change over time, choline differences that appear at 3 months and is related to somatic symptoms.

Magnetic Resonance Spectroscopy of Traumatic Brain Injury and Subconcussive Hits: A Systematic Review and Meta-Analysis.

Magnetic resonance spectroscopy (MRS) is a non-invasive technique used to study metabolites in the brain. MRS findings in traumatic brain injury (TBI) and subconcussive hit literature have been mixed. The most common observation is a decrease in N-acetyl-aspartate (NAA), traditionally considered a marker of neuronal integrity. Other metabolites, however, such as creatine (Cr), choline (Cho), glutamate+glutamine (Glx) and myo-inositol (mI) have shown inconsistent changes in these populations. The objective of this systematic review and meta-analysis was to synthesize MRS literature in brain injury and explore factors (biological factors such as brain region, injury severity, time since injury, demographics and technical methodological factors such as field strength, acquisition parameters, analysis approach) that may contribute to differential findings. One hundred and thirty-eight studies met inclusion criteria for the systematic review and of those, 62 NAA, 24 Cr, 49 Cho, 18 Glx, and 21 mI studies met inclusion criteria for meta-analysis. A random effects model was used for meta-analyses with brain region as a subgroup for each of the five metabolites studied. Meta-regression was used to examine the influence of potential moderators including injury severity, time since injury, age, sex, tissue composition, and methodological factors. In this analysis of 1428 unique brain-injured subjects and 1132 controls, the corpus callosum was identified as a brain region highly susceptible to metabolite alteration. NAA was consistently decreased in TBI of all severities, but not in subconcussive hits. Cho and mI were found to be increased in moderate-to-severe TBI but not in mild TBI. Glx and Cr were largely unaffected, but did show alterations in certain conditions.

Impact of Pump Speed on Hemodynamics With Exercise in Continuous Flow Ventricular Assist Device Patients.

At fixed speed, the spontaneous increase in pump flow accompanying exercise in patients with continuous flow left ventricular assist devices (cfLVADs) is slight in comparison to normal physiologic response, limiting exercise capacity. We systematically exercised 14 patients implanted with an isolated HeartWare HVAD undergoing routine right heart catheterization at baseline and at maximal safe pump speed. In addition to hemodynamics, mixed venous oxygen saturation (SvO2), echocardiography and noninvasive mean arterial pressure, and heart rate were measured. Significantly greater pump flows were achieved with maximum pump speed compared with baseline speed at rest (mean ± standard deviation [SD]: 5.0 ± 0.7 vs. 4.6 ± 0.8 L/min) and peak exercise (6.7 ± 1.0 vs. 5.9 ± 0.9 L/min, p = 0.001). Pulmonary capillary wedge pressure was significantly reduced with maximum pump speed compared to baseline pump speed at rest (10 ± 4 vs. 15 ± 5 mmHg, p < 0.001) and peak exercise (27 ± 8 vs. 30 ± 8 mmHg, p = 0.002). Mixed venous oxygen saturation decreased with exercise (p < 0.001) but was unaffected by changes in pump speed. In summary, although higher pump speeds synergistically augment the increase in pump flow associated with exercise and blunt the exercise-induced rise in left heart filling pressures, elevated filling pressures and markedly diminished SvO2 persist at maximal safe pump speed, suggesting that physiologic flow increases are not met by isolated cfLVADs in the supported failing heart.

Comparison of pain and emotional symptoms in soldiers with polytrauma: unique aspects of blast exposure.

OBJECTIVES: To compare the physical and emotional presentation and pain treatment outcomes of service members who sustained polytrauma secondary to blast with those of soldiers injured by other means. DESIGN: Retrospective medical record review. SETTING AND PATIENTS: One of four Veterans Affairs multidisciplinary inpatient Polytrauma Rehabilitation Centers. One hundred twenty-eight Operation Enduring Freedom and Operation Iraqi Freedom military personnel with serious polytrauma injuries and concomitant pain categorized into three groups based on type of injuries: blast injuries, combat injuries other than blast, and noncombat, nonblast injuries. INTERVENTIONS: Intensive, interdisciplinary inpatient rehabilitation and pain treatment. OUTCOME MEASURES: Pain intensity ratings; Functional Independence Measure scores; Rancho Los Amigos levels; and opioid analgesic doses. RESULTS: Service members injured via blast demonstrated a broader spectrum of physical injuries, higher levels of admission and discharge opioid analgesic use, reduced improvement in pain intensity following treatment, and much higher rates of posttraumatic stress disorder and other psychiatric diagnoses than those injured via other means. CONCLUSIONS: Blast injury may be associated with differential physical, emotional, and pain-related symptoms that pose increased challenges for successful treatment.

Assessment and treatment of pain associated with combat-related polytrauma.

Due to the high rates of blast injuries sustained during operations in Iraq and Afghanistan, the number of soldiers returning with massive and multiple wounds is unprecedented. While casualty survival rates have improved dramatically, the extent and impact of these wounds on soldiers' functioning pose unique challenges for their rehabilitation. Pain is highly prevalent in these individuals with polytrauma injuries and is a source of suffering, as well as an impediment to rehabilitation. However, there are a number of obstacles to effective pain treatment in this group of war-injured, including their multiple and severe injuries, the high prevalence of brain injuries, cognitive impairments and emotional distress, the prolonged and intensive rehabilitation process, and the frequent need for repeated follow-up surgeries. As a result, we believe that a comprehensive, interdisciplinary approach to pain treatment is required. In this article we describe the model of pain care that has evolved at the Tampa Polytrauma Rehabilitation Center, which incorporates medical, rehabilitative, cognitive-behavioral, and interventional treatments targeting pain intensity as well as pain-related impairments and coping. We include a case study illustrating some key aspects of our approach.

Traumatic brain injury, polytrauma, and pain: challenges and treatment strategies for the polytrauma rehabilitation.

PROBLEM: Chronic pain conditions are common sequelae of traumatic brain injury (TBI). Unfortunately, the incidence of TBI among personnel deployed for Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) is significant, and there is growing evidence that ongoing pain, particularly headaches, will be a primary concern for these individuals. OBJECTIVE: This article synthesizes empirical data from civilian and veteran populations and clinical experience with OEF/OIF personnel with polytrauma to provide recommendations for the assessment and treatment of chronic pain among those with TBI. CONCLUSIONS: The available data signal the need for the incorporation of early and aggressive pain management strategies into existing treatment models. Challenges to providing effective pain management for OEF/OIF veterans are numerous and include comorbid cognitive, medical, and emotional impairments that complicate readjustment to civilian life. It is likely that the problem of polytrauma pain and associated comorbid conditions such as posttraumatic stress disorder and postconcussive syndrome will require the development of integrated approaches to clinical care which bridge traditional subspecialty divisions. A proposed model of treatment is presented.

Measuring wildland fire fighter performance with wearable technology.

Wildland (rural) fire fighting is a physically demanding and hazardous occupation. An observational study was conducted to explore the use of new technologies for the field study of fire fighters at wildfires and to understand the work pressures of wildland fire fighting. The research was carried out with two fire fighters at real fires wearing microphones, miniature video cameras, heart rate monitors and GPS units to record their actions and location at wildfire events. The fire fighters were exposed to high physiological workloads (heart rates of up to 180 beats per minute) and walked considerable distances at the fires. Results from this study have been used in presentations to fire fighters and non-operational fire personnel to understand the pressures fire fighters are under and how others complete the fire fighting tasks.

Effect of exercise and pump speed modulation on invasive hemodynamics in patients with centrifugal continuous-flow left ventricular assist devices.

BACKGROUND: Continuous-flow left ventricular assist devices (CF-LVADs) improve functional capacity in patients with end-stage heart failure. Pump output can be increased by increased pump speed as well as changes in loading conditions. METHODS: The effect of exercise on invasive hemodynamics was studied in two study protocols. The first examined exercise at fixed pump speed (n = 8) and the second with progressive pump speed increase (n = 11). Patients underwent simultaneous right-heart catheterization, mixed venous saturation, echocardiography and mean arterial pressure monitoring. Before exercise, a ramp speed study was performed in all patients. Patients then undertook symptom-limited supine bicycle exercise. RESULTS: Upward titration of pump speed at rest (by 11.6 ± 8.6% from baseline) increased pump flow from 5.3 ± 1.0 to 6.3 ± 1.0 liters/min (18.9% increase, p < 0.001) and decreased pulmonary capillary wedge pressure (PCWP; 13.6 ± 5.4 to 8.9 ± 4.1 mm Hg, p < 0.001). Exercise increased pump flow to a similar extent as pump speed change alone (to 6.2 ± 1.0 liters/min, p < 0.001), but resulted in increased right- and left-heart filling pressures (right atrial pressure [RAP]: 16.6 ± 7.5 mm Hg, p < 0.001; PCWP 24.8 ± 6.7 mm Hg, p < 0.001). Concomitant pump speed increase with exercise enhanced the pump flow increase (to 7.0 ± 1.4 liters/min, p < 0.001) in Protocol 2, but did not alleviate the increase in pre-load (RAP: 20.5 ± 8.0 mm Hg, p = 0.07; PCWP: 26.8 ± 12.7 mm Hg; p = 0.47). Serum lactate and NT-proBNP levels increased significantly with exercise. CONCLUSIONS: Pump flow increases with up-titration of pump speed and with exercise. Although increased pump speed decreases filling pressures at rest, the benefit is not seen with exercise despite concurrent up-titration of pump speed.

Women and the implantable cardioverter defibrillator: a lifespan perspective on key psychosocial issues.

The clinical success of the implantable cardioverter defibrillator (ICD) in reducing mortality suggests that more women will be receiving ICDs in the future. The impact of ICD therapy in women is unique in western societies; the ICDs scar and lump in the pectoral area can lead to body image concerns due to the emphasis on women's physical attractiveness. Social support and roles are challenged because women's reaction to stress has been characterized by a "tend and befriend" response, involving cultivating and utilizing social networks, rather than the "fight or flight" response more typical of men. In addition, a woman's identity as a caretaker and caregiver can be threatened by the actual and perceived activity limitations imposed by the ICD or the underlying heart condition. Finally, reproductive and sexual health are important issues, as 25 to 50% of patients with ICDs report concerns in this area, but also report discomfort in discussing these concerns with their health care providers. The purpose of the present paper is to review the relevant literature and to identify the unique impact of the psychosocial issues of body image, social support and roles, and sexual development and reproductive functioning for women with ICDs across the lifespan. In the absence of complete empirical research data on the impact of these concerns, hypotheses to test in future research are offered.

Management responsibilities in the retirement village industry: a New Zealand study.

The Retirement Village/Rest Home industry is growing rapidly. Many of those fulfilling managerial roles within this industry do not appear to have management qualifications or prior managerial experience outside the public sector health system. If the industry is to effectively manage anticipated growth, managers may need to update their qualifications and knowledge base to ensure that they possess the skills and abilities required to meet changing business needs. This paper reports on an exploratory study designed to gather information that identifies the primary duties and responsibilites of retirement village managers and nurse managers, and their essential and desirable skills, attributes, and characteristics.

Body position and activity, but not heart rate, affect pump flows in patients with continuous-flow left ventricular assist devices.

OBJECTIVES: The aim of this study was to determine the contribution of pre-load and heart rate to pump flow in patients implanted with continuous-flow left ventricular assist devices (cfLVADs). BACKGROUND: Although it is known that cfLVAD pump flow increases with exercise, it is unclear if this increment is driven by increased heart rate, augmented intrinsic ventricular contraction, or enhanced venous return. METHODS: Two studies were performed in patients implanted with the HeartWare HVAD. In 11 patients, paced heart rate was increased to approximately 40 beats/min above baseline and then down to approximately 30 beats/min below baseline pacing rate (in pacemaker-dependent patients). Ten patients underwent tilt-table testing at 30°, 60°, and 80° passive head-up tilt for 3 min and then for a further 3 min after ankle flexion exercise. This regimen was repeated at 20° passive head-down tilt. Pump parameters, noninvasive hemodynamics, and 2-dimensional echocardiographic measures were recorded. RESULTS: Heart rate alteration by pacing did not affect LVAD flows or LV dimensions. LVAD pump flow decreased from baseline 4.9 ± 0.6 l/min to approximately 4.5 ± 0.5 l/min at each level of head-up tilt (p < 0.0001 analysis of variance). With active ankle flexion, LVAD flow returned to baseline. There was no significant change in flow with a 20° head-down tilt with or without ankle flexion exercise. There were no suction events. CONCLUSIONS: Centrifugal cfLVAD flows are not significantly affected by changes in heart rate, but they change significantly with body position and passive filling. Previously demonstrated exercise-induced changes in pump flows may be related to altered loading conditions, rather than changes in heart rate.

Implementing and integrating a clinically driven electronic medical record for radiation oncology in a large medical enterprise.

PURPOSE/OBJECTIVE: While our department is heavily invested in computer-based treatment planning, we historically relied on paper-based charts for management of Radiation Oncology patients. In early 2009, we initiated the process of conversion to an electronic medical record (EMR) eliminating the need for paper charts. Key goals included the ability to readily access information wherever and whenever needed, without compromising safety, treatment quality, confidentiality, or productivity. METHODOLOGY: In February, 2009, we formed a multi-disciplinary team of Radiation Oncology physicians, nurses, therapists, administrators, physicists/dosimetrists, and information technology (IT) specialists, along with staff from the Duke Health System IT department. The team identified all existing processes and associated information/reports, established the framework for the EMR system and generated, tested and implemented specific EMR processes. RESULTS: Two broad classes of information were identified: information which must be readily accessed by anyone in the health system versus that used solely within the Radiation Oncology department. Examples of the former are consultation reports, weekly treatment check notes, and treatment summaries; the latter includes treatment plans, daily therapy records, and quality assurance reports. To manage the former, we utilized the enterprise-wide system, which required an intensive effort to design and implement procedures to export information from Radiation Oncology into that system. To manage "Radiation Oncology" data, we used our existing system (ARIA, Varian Medical Systems.) The ability to access both systems simultaneously from a single workstation (WS) was essential, requiring new WS and modified software. As of January, 2010, all new treatments were managed solely with an EMR. We find that an EMR makes information more widely accessible and does not compromise patient safety, treatment quality, or confidentiality. However, compared to paper charts, time required by clinicians to access/enter patient information has substantially increased. While productivity is improving with experience, substantial growth will require better integration of the system components, decreased access times, and improved user interfaces. $127K was spent on new hardware and software; elimination of paper yields projected savings of $21K/year. One year after conversion to an EMR, more than 90% of department staff favored the EMR over the previous paper charts. CONCLUSION: Successful implementation of a Radiation Oncology EMR required not only the effort and commitment of all functions of the department, but support from senior health system management, corporate IT, and vendors. Realization of the full benefits of an EMR will require experience, faster/better integrated software, and continual improvement in underlying clinical processes.

Effect of alteration in pump speed on pump output and left ventricular filling with continuous-flow left ventricular assist device.

Third-generation continuous-flow left ventricular assist devices (LVAD) provide reduced pulsatility flow. We examined the safe working range for LVAD pump speed and the effect on pump output and cardiac function in 13 stable outpatients with VentrAssist-LVAD (Ventracor Ltd, Australia). Pump speed was decreased from a baseline mean of 2,073 ± 86 revolutions per minute (RPM, with corresponding mean flow of 5.59 ± 1.18 L/min, mean ± standard deviation) to an average low-speed of 1,835 ± 55 RPM (corresponding flow 4.68 ± 0.99 L/min) and up to high-speed of 2,315 ± 66 RPM (corresponding flow 6.30 ± 1.29 L/min). There was a strong linear relationship between alteration in speed and flow rates (r(2) = 0.89, p < 0.00001) but marked interpatient variation. Downward titration to preset minimum 1,800 RPM was achieved in 9/13 (69%) and upward titration to the preset maximum 2,400 RPM was achieved in 4/13 (31%). Upward titration was stopped due to ventricular suction or nonsustained ventricular tachycardia (VT) in 4/13 (31%). Ventricular suction or VT (in 4/13) tended to be more common in patients with poor right ventricular (RV) function (p = 0.07). In summary, pump flow is stable within a relatively small speed range and should not be altered without close monitoring due to variation in response between patients, particularly with concomitant RV impairment.

Anxiety and marital adjustment in patients with implantable cardioverter defibrillator and their spouses.

PURPOSE: Device-related fears are a pervasive psychosocial difficulty that patients with implantable cardioverter defibrillators (ICDs) experience. Spouses also encounter anxieties that may influence patient and spouse adjustment. This study examined anxiety and marital adjustment among ICD patients and spouses, as well as intersex differences between female and male patients. METHODS: Patients and their spouses (N=62) completed separate individual assessment batteries regarding demographics, death anxiety, shock anxiety, general anxiety, and marital adjustment at a single time point during outpatient cardiology visits. RESULTS: Analyses revealed similar general anxiety and marital adjustment among participants, although spouses reported greater shock anxiety than did patients (P = .045). Female ICD patients reported more anxiety related to death and shock and received more shocks, despite equivalent indices of medical severity (P = .002). CONCLUSIONS: This study suggests that spouses of ICD patients experience higher levels of shock anxiety than do patients themselves and that female ICD patients experience higher levels of shock anxiety and death (anxiety than do male patients. Results suggest future research of device specific anxiety and clinical attention devoted to ICD patient spouses and female ICD patients.

Pain and combat injuries in soldiers returning from Operations Enduring Freedom and Iraqi Freedom: implications for research and practice.

Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have resulted in a growing number of seriously injured soldiers who are evacuated to the United States for comprehensive medical care. Trauma-related pain is an almost universal problem among these war-injured soldiers, and several military and Department of Veterans Affairs initiatives have been implemented to enhance pain care across the continuum of medical services. This article describes several innovative approaches for improving the pain care provided to OEF and OIF military personnel during acute stabilization, transport, medical-surgical treatment, and rehabilitation and presents summary data characterizing the soldiers, pain management services provided, and associated outcomes. We also identify some of the pain assessment, classification, and treatment challenges emerging from work with this population and provide recommendations for future research and practice priorities.

Preliminary evaluation of reliability and criterion validity of Actiwatch-Score.

The restoration of normal physical activity is a primary objective of most chronic pain rehabilitative interventions, yet few clinically practical objective measures of activation exist. Actigraphy is one technology that promises to fill this void in the field of pain outcomes assessment. This study evaluates the measurement properties of one of several commercially available actigraphs: the Actiwatch-Score (AW-S). We conducted separate trials to examine concordance between units when worn concurrently at the same and different body sites and to compare the AW-S to a validated optical three-dimensional motion-tracking system. The data indicate that the AW-S has excellent interunit reliability and good criterion validity, but its intersite reliability varies with activity type. These results suggest that this device, and those like it, warrants further investigation and is likely to yield valuable data regarding the optimal application of this technology.

Pain among veterans of Operations Enduring Freedom and Iraqi Freedom.

OBJECTIVE: Pain is one of the most frequently reported symptoms by veterans returning from recent overseas military actions. The purpose of the current study was to obtain a preliminary estimate of the prevalence and severity of pain among veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF; N=970). The demographic, etiologic, and diagnostic characteristics of 100 veterans with moderate to severe chronic pain conditions were examined in order to provide a description of this new group of pain patients. DESIGN: This was a historical cohort study that utilized electronic medical record review for all data collection. PATIENTS: All registered OEF/OIF veterans seeking treatment at a Southeastern Veterans' Affairs medical center were included in the initial cohort. In order to describe the characteristics of those with clinically significant pain, 100 veterans were randomly sampled from the subset of patients who reported moderate to severe chronic pain intensity during a medical visit (N=219). RESULTS: Approximately 47% of veterans whose charts included pain score documentation (N=793) reported at least a mild level of current pain. Moderate to severe pain intensity was recorded for 28% (N=219) of those in the initial cohort with pain scores. Diagnoses of musculoskeletal and connective tissue disorders were recorded for 82% of those with chronic conditions (i.e., duration>or=1 month). CONCLUSIONS: The results of this preliminary study suggest that a substantial percentage of OEF/OIF veterans will experience clinically significant pain following their military service.