bluuebunny/crossref_metadata_2025 huggingface dataset:
Failing to Plan Is Planning to Fail: Improving the Quality of Care With Survivorship Care Plans
Authors: Earle Craig C.
Published: November 2006

The recent Institute of Medicine report “From Cancer Patient to Cancer Survivor: Lost in Transition” recommended the creation of survivorship care plans for patients as they complete primary therapy for cancer to ensure clarity for all involved about patients’ diagnoses, treatments received, and surveillance plans. Any previously existing follow-up guidelines for cancer survivors have been largely restricted to surveillance for recurrence of the primary disease. An important message of the Institute of Medicine report is that survivorship care plans must surpass this and address the chronic effects of cancer (pain, fatigue, premature menopause, depression/anxiety), monitoring for and preventing late effects like osteoporosis, heart disease, and second malignancies, and promoting healthy lifestyles. It should explicitly identify the providers responsible for each aspect of ongoing care and provide information on resources available for psychosocial and other practical issues that may arise as a result of the prior cancer diagnosis. Although having some sort of a plan is clearly necessary to achieve high quality care, there are practical barriers to formal off-treatment consultations and the creation of written documents that may become part of the medical record. This article reviews the elements of the proposed survivorship care plan and discusses areas of research and development needed to make them part of standard oncology practice.
Survivorship Perspectives and Advocacy
Authors: Hoffman Barbara , Stovall Ellen
Published: November 2006

From the moment of diagnosis, a cancer survivor faces serious life-altering decisions. Survivors who are informed about their options and who feel they have personal control over decision making generally perceive a higher quality of life than those who feel less informed and less in control. Health care providers are in a unique position to define a survivor's cancer care and to guide a survivor through treatment and post-treatment care. By implementing survivorship care plans and directing their patients to survivorship resources, health care providers can advocate for survivors and teach them to be effective self-advocates.
Looking Beyond Survival: How Are We Looking at Survivorship?
Authors: Grunfeld Eva
Published: November 2006

Background

The prevalence of cancer survivors is increasing worldwide. This creates the imperative to look beyond cancer survival to cancer survivorship. This review explores cancer survivorship from an international perspective in two ways: from a cancer control perspective through a review of cancer control strategies and from a cancer care perspective through a review of clinical practice guidelines and research on cancer follow-up care.

Results

Many national cancer control strategies or cancer charities consider survivorship obliquely, primarily under the umbrellas of quality of life and rehabilitation. Few have well-developed policies or plans specifically directed at survivorship. Cancer follow-up care is recognized internationally as a pressing health care issue. Many countries have tested new and innovative models to deliver follow-up care. Similarly, many countries have developed guidelines that specifically address follow-up care. Few studies or guidelines address the broader, multifaceted aspects of cancer survivorship.

Discussion

This review suggests that research and recognition of cancer survivorship as a unique phase of the cancer care trajectory need to be improved. In many of the poorer countries of the world, the imperative remains the basics of cancer care: timely diagnosis, access to treatment, and alleviation of suffering.
Responding to Employment Concerns of Cancer Survivors
Authors: Short Pamela Farley , Vargo Mary M.
Published: November 2006

The report on cancer survivorship recently released by the Institute of Medicine called on providers to become familiar with the employment rights of survivors, to offer them information about employment rights and programs, and to help minimize the adverse effects of cancer on employment. This review is designed to help providers respond to the Institute of Medicine's recommendations by describing relevant employment and health insurance protections, nationally accessible services and information sources for survivors, functional limitations that may affect survivors' work, and a variety of rehabilitation services that may be helpful for survivors with disabling residual effects of cancer and its treatment. It also suggests directions for further efforts on the part of public and private cancer organizations, researchers, and clinicians to address the employment concerns of survivors.
Enhancing Research on Cancer Survivors
Authors: Ayanian John Z. , Jacobsen Paul B.
Published: November 2006

The United States devotes substantial resources to understanding the etiologies of cancer and improving treatments, but much less research has focused on the needs of cancer survivors after they have completed active treatment. This article augments findings from the Institute of Medicine about cancer survivorship research and ways to enhance quality of life and quality of care. Studies of cancer survivors should focus on mechanisms and risk factors for impaired quality of life and evaluate interventions to improve this domain. Research to improve quality of care should concentrate on survivorship care plans, surveillance tests, respective roles of primary and specialty care, and performance measures related to survivorship care. Opportunities to expand research on cancer survivors include clinical trials, large cohort studies, cancer registries, and national surveys. Research to understand the needs of cancer survivors will provide a foundation for effective programs to meet these needs.
Acute Amphotericin B Overdose
Authors: Burke Douglas , Lal Rajiv , Finkel Kevin W , Samuels Joshua , Foringer John R
Published: November 2006

Objective:

To report the clinical course of a woman with cryptococcal meningitis and no previous cardiac disease who developed a fatal cardiac arrhythmia after an acute overdose of amphotericin B and to review its toxicity.

Case Summary:

A 41-year-old woman with a history of proliferative glomerulonephritis from systemic lupus erythematosus was admitted with a diagnosis of cryptococcal meningitis. Liposomal amphotericin B was prescribed at the standard dose of 5 mg/kg/day; however, amphotericin B deoxycholate 5 mg/kg was inadvertently administered (usual dose of the deoxycholate formulation is 0.5–0.8 mg/kg/day). The patient developed cardiac arrhythmias, acute renal failure, and anemia. The medication error was noticed after she had received 2 doses of amphotericin B deoxycholate, and it was then discontinued. Despite treatment in the intensive care unit, the woman died on the sixth day after admission.

Discussion:

Amphotericin B deoxycholate has been reported to produce significant cardiac toxicity, with ventricular arrhythmias and bradycardia reported in overdoses in children and in adults with preexisting cardiac disease, even when administered in conventional dosages and infusion rates. Use of the Naranjo probability scale indicated a highly probable relationship between the observed cardiac toxicity and amphotericin B deoxycholate therapy in this patient.

Conclusions:

Given the fulminant course of amphotericin B deoxycholate overdosage and lack of effective therapy, stringent safeguards against its improper administration should be in place.
Psychometric Analysis of a Scale Assessing Self-Efficacy for Cultural Competence in Patient Counseling
Authors: Assemi Mitra , Cullander Chris , Hudmon Karen Suchanek
Published: November 2006

Background:

The Accreditation Council for Pharmacy Education adopted revised accreditation standards and guidelines for the PharmD degree program in January 2006. The revised standards mandate the inclusion of cultural competence in pharmacy curricula. Assessment tools to evaluate the impact of training are needed.

Objective:

To examine the psychometric properties of a 12 item scale designed to estimate the impact of cultural competence training on pharmacy students' self-efficacy in providing culturally appropriate patient care.

Methods:

A 12 item scale to assess the impact of an elective course on pharmacy students' (N = 175; 173 analyzable) perceived self-efficacy in providing culturally competent patient care was used before and after students completed the training. Principal components analysis was conducted to examine the underlying structure of the scale, and the Cronbach α statistic was computed as an estimate of internal consistency. Pre- versus posttraining responses for each item and for the total scale scores were compared as an indicator of concurrent validity.

Results:

The principal components analysis yielded a one-component solution, “self-efficacy for cultural competence,” which included all 12 contributing items and accounted for 46% of the total variance. Item communalities ranged from 0.25 to 0.58. Component loadings ranged from 0.50 to 0.76. Overall, the scale exhibited a Cronbach α estimate of internal consistency of 0.89. Posttraining scores were significantly higher than pretraining scores for both the total scale scores (posttest and pretest mean ± SD score = 47.96 ± 5.15 and 34.21 ± 6.19, respectively; p < 0.001) and for each item (p values < 0.001). These comparisons provide evidence of concurrent validity.

Conclusions:

Our results suggest that our 12 item scale exhibits acceptable psychometric properties and is a useful tool for estimating the impact of cultural competence training on pharmacy students' perceived self-efficacy for providing culturally competent care and services.
Neurology and Neurosurgery Clinical Pharmacy Practice: Ignorance, Phobia, or Progress?
Authors: Welty Timothy E
Published: November 2006

2006 marks the 40th year of publication for The Annals. Over that time, The Annals has been an important contributor to the development of clinical pharmacy. Throughout 2006, we are publishing articles reflecting on the history of clinical pharmacy through the eyes of practitioners, including those pioneering clinical pharmacy, as well as those who have more recently entered the profession and a well-established specialty. In addition, we are also presenting articles and editorials from the early history of The Annals that have given direction and shape to the practice of clinical pharmacy (see page 2240).
SPECIAL SECTION: Task Complexity in Emergency Medical Care and Its Implications for Team Coordination
Authors: Xiao Yan , Hunter William A. , Mackenzie Colin F. , Jefferies Nicolas J. , Horst Richard L. , Group Lotas
Published: November 2006

To elicit components of task complexity in emergency medical care, a study was conducted to contrast one medical procedure with two levels of task urgency in trauma patient resuscitation. Videotapes of actual resuscitation were reviewed to extract task characteristics of the procedure. Two levels of urgency were compared in the following areas: patient status, technical difficulty of tasks, the amount of available patient monitoring information, and the pace of work. Four components of task complexity in emergency medical care were identified: multiple and concurrent tasks, uncertainty, changing plans, and compressed work procedures and high workload. These components of task complexity pose challenges to team functions and can lead to problems in team coordination, such as conflicts in goals, tasks, and access to the patient. Training to increase explicit communications and improvements in the design of work procedures are necessary in order to meet the challenges of task complexity.
Keyboard Reaction Force and Finger Flexor Electromyograms during Computer Keyboard Work
Authors: Martin Bernard J. , Armstrong Thomas J. , Foulke James A. , Natarajan Sivakumaran , Klinenberg Edward , Serina Elaine , Rempel David
Published: November 2006

This study examines the relationship between forearm EMGs and keyboard reaction forces in 10 people during keyboard tasks performed at a comfortable speed. A linear fit of EMG force data for each person and finger was calculated during static fingertip loading. An average r2 of .71 was observed for forces below 50% of the maximal voluntary contraction (MVC). These regressions were used to characterize EMG data in force units during the typing task. Averaged peak reaction forces measured during typing ranged from 3.33 N (thumb) to 1.84 N (little finger), with an overall average of 2.54 N, which represents about 10% MVC and 5.4 times the key switch make force (0.47 N). Individual peak or mean finger forces obtained from EMG were greater (1.2 to 3.2 times) than force measurements; hence the range of r2 for EMG force was .10 to .46. A closer correspondence between EMG and peak force was obtained using EMG averaged across all fingers. For 5 of the participants the force computed from EMG was within ±20% of the reaction force. For the other 5 participants forces were overestimated. For 9 participants the difference between EMG estimated force and the reaction force was less than 13% MVC. It is suggested that the difference between EMG and finger force partly results from the amount of muscle load not captured by the measured applied force.
SPECIAL SECTION: Comparison of Self-Reporting of Deficiencies in Airway Management with Video Analyses of Actual Performance
Authors: Mackenzie Colin F. , Jefferies Nicholas J. , Hunter William A. , Bernhard William N. , Xiao Yan , Group Lotas , Horst Richard
Published: November 2006

We compared the performance deficiencies of airway management captured by three types of self-reports with those identified through video analysis. The three types of self-reports were the anesthesia record (a patient record constructed during the course of treatment), the anesthesia quality assurance (AQA) report (a retrospective report as a part of the trauma center's quality assurance process), and a posttrauma treatment questionnaire (PTQ), which was completed immediately after the case for the purposes of this research. Video analysis of 48 patient encounters identified 28 performance deficiencies related to airway management in 11 cases (23%). The performance deficiencies took the form of task omissions or practices that lessened the margin of patient safety. In comparison, AQA reports identified none of these performance deficiencies, the anesthesia records identified 2 (of 28), and the PTQs suggested contributory factors and corrective measures for 5 deficiencies. Furthermore, video analysis provided information about the context of and factors contributing to the identified performance deficiencies, such as failures in adherence to standard operating procedures and in communications.
Relationships between Ambient Sounds and the Accuracy of Pharmacists' Prescription-Filling Performance
Authors: Flynn Elizabeth Allan , Barker Kenneth N. , Gibson J. Tyrone , Pearson Robert E. , Smith Leo A. , Berger Bruce A.
Published: November 2006

Associations between ambient sounds and accuracy of pharmacists' prescription-filling performance in a pharmacy was studied. Pharmacists were videotaped as they filled prescriptions each workday for 23 days. Each filled prescription was inspected by the investigator. Deviations from the physician's written order were considered errors. Videotape analysis was used to detect unpredictable, predictable, uncontrollable, and controllable sounds. A within-subjects case control study design was employed to determine whether the frequency of ambient sounds was significantly different when prescriptions with errors, compared with those without errors, were filled. Loudness, in terms of equivalent sound levels (Leq) for each half hour, was analyzed for a relationship to dispensing error rate. A mean dispensing error rate of 3.23% was found. Unpredictable sounds, controllable sounds, and noise had a significant effect on pharmacists which resulted in a decreased dispensing error rate. These results suggest that the quality of pharmacists' performance is not adversely affected by ambient sound. As equivalent sound levels increased, the error rate increased to a point, then decreased.
The Influence of Flooring on Standing Balance among Older Persons
Authors: Redfern Mark S. , Moore Pamela L. , Yarsky Christine M.
Published: November 2006

This study investigated the effects of flooring on balance during quiet standing in healthy young and older participants. Seven flooring conditions were examined, including a hard tile floor and combinations of low-pile and high-pile carpet with urethane foam and rubber padding. The resulting floors provided a variety of compliant surfaces, ranging from very soft to hard. Participants stood during three separate visual conditions: eyes open, eyes closed, and looking at a moving visual surround. Three measures of postural sway were calculated using center of pressure recordings during the trials. The results showed that the amplitude of sway was higher in the older than in the younger participants, particularly in the moving visual surround condition. Flooring compliance was found to have an effect on sway during moving visual environments, with the largest effects found among the older participants. Softer floors increased the amount of sway in the older participants. These results suggest that floor compliance influences standing postural stability in older people, particularly in destabilizing visual environments.
Multiaccommodative Stimuli in VR Systems: Problems & Solutions
Authors: Marran Lynn , Schor Clifton
Published: November 2006

Virtual reality environments can introduce multiple and sometimes conflicting accommodative stimuli. For instance, with the high-powered lenses commonly used in head-mounted displays, small discrepancies in screen lens placement, caused by manufacturer error or user adjustment focus error, can change the focal depths of the image by a couple of diopters. This can introduce a binocular accommodative stimulus or, if the displacement between the two screens is unequal, an unequal (anisometropic) accommodative stimulus for the two eyes. Systems that allow simultaneous viewing of virtual and real images can also introduce a conflict in accommodative stimuli: When real and virtual images are at different focal planes, both cannot be in focus at the same time, though they may appear to be in similar locations in space. In this paper four unique designs are described that minimize the range of accommodative stimuli and maximize the visual system's ability to cope efficiently with the focus conflicts that remain: pinhole optics, monocular lens addition combined with aniso-accommodation, chromatic bifocal, and bifocal lens system. The advantages and disadvantages of each design are described and recommendation for design choice is given after consideration of the end use of the virtual reality system (e.g., low or high end, entertainment, technical, or medical use). The appropriate design modifications should allow greater user comfort and better performance.
Effects of Team Size on the Maximum Weight Bar Lifting Strength of Military Personnel
Authors: Sharp Marilyn A. , Rice Valerie J. , Nindl Bradley C. , Williamson Tania L.
Published: November 2006

Teamwork is an essential element in the majority of critical Army lifting tasks. Therefore, an understanding of the relationship between individual and team lifting capacity is of great tactical importance. Twenty-three male and 17 female U.S. Army soldiers were randomly assigned to single- and mixed-gender teams of two, three, and four persons. Individual lifting strength was the one-repetition-maximum (1RM) load lifted from floor to knuckle height using a weight bar. A square-shaped bar was used for two- and four-person lifting, and a triangular-shaped bar was used for three-person lifting. Team lifting strength as a percentage of the sum of individual lifting strength (%sum) did not change with team size. The %sum for teams of men (87.3%) was less than for teams of women (91.1%, p < 0.05). The %sums for both single-gender teams (all men and all women) were greater (p < 0.01) than for mixed-gender teams (80.2%). The number of people lifting a large object was increased to four with no decrease in the effectiveness of the individual lifter beyond that found for two persons. The 1RM loads presented in this paper were lifted under ideal conditions by young soldiers and do not represent norms for an industrial population.
The Effect of Valve Handwheel Type, Operating Plane, and Grasping Posture on Peak Torque Strength of Young Men and Women
Authors: Shih Yuh-Chuan , Wang Mao-Jiun J. , Chang Chih-Hong
Published: November 2006

An experiment was designed to assess the factors affecting the operation of valve handwheels. Forty volunteers (20 men and 20 women) participated in this study. A nested-factorial experimental design was employed. Handwheel type (smooth, curved, or knurled rim), operating plane (sagittal, frontal, or transverse plane), grasping posture (power or precision grasp), and operating direction (clockwise or counterclockwise) were found to have significant effects on the (maximum volitional torque exertion [MVTE)). A power grasp exerted more force than did a precision grasp. A smooth-rim handwheel oriented in the frontal plane resulted in the least MVTE. Counterclockwise torque exertion was significantly greater than clockwise torque exertion, but the difference was not very large. MVTE for women (7.9 Nm) was about 66% of that for men (12.0 Nm).
Artificial Looming Yields Improved Performance over Lateral Motion: Implications for Stereoscopic Display Techniques
Authors: Schmidt William C.
Published: November 2006

In the natural world, a number of visual cues indicate that an item is quickly approaching the perceiver. Binocular disparity is one cue for depth, and it has been demonstrated that abrupt changes in disparity, artificially unaccompanied by correlated depth cues, are capable of causing the perception of looming for the observer. An experiment involving 38 undergraduates, using a computer-controlled stereoscopic display, examined the ability of above-threshold changes in disparity (artificial looming) to facilitate response time and accuracy for observers engaged in an object-enumeration task within a cluttered display. Compared with performance using the same stimuli without disparity information (lateral motion), participants were more accurate regardless of the disparity level (9, 12, 24, or 48 minutes of arc) and faster at the two lowest levels of disparity. Participants showed the classic subitizing function, suggesting that target stimuli presented with motion information were segregated from otherwise identical distractor items. It is proposed that binocular disparity information can act as a valid location cuing method in stereoscopic computer displays in which form and color information are to be preserved.
Aging and Decision Making: Driving-Related Problem Solving
Authors: Walker Neff , Fain Bradley , Fisk Arthur D. , Mcguire Christy L.
Published: November 2006

We examined age-related effects on decision making in a task environment familiar to most younger and older adults. Participants made route-selection decisions in real time. Participants received information about traffic density and expected speed limits of main and alternative routes, from which they determined the optimality of their present route versus alternative routes. The experiment evaluated the effects of information type, amount of congestion, alternative route speed limit, and age on speed and quality of decision making. Measures of optimal route selection revealed main effects of alternative route speed limit, congestion level, and message type, but there was not a main effect of age, and age did not interact with any variable. In terms of decision speed (but not quality of decision making), older participants were slower, and age interacted with alternative route speed and with message type. The data are interpreted in relation to previous data examining everyday problem solving and aging.
Enduring Critical Period Plasticity Visualized by Transcranial Flavoprotein Imaging in Mouse Primary Visual Cortex
Authors: Tohmi Manavu , Kitaura Hiroki , Komagata Seiji , Kudoh Masaharu , Shibuki Katsuei
Published: November 2006

Experience-dependent plasticity in the visual cortex was investigated using transcranial flavoprotein fluorescence imaging in mice anesthetized with urethane. On- and off-responses in the primary visual cortex were elicited by visual stimuli. Fluorescence responses and field potentials elicited by grating patterns decreased similarly as contrasts of visual stimuli were reduced. Fluorescence responses also decreased as spatial frequency of grating stimuli increased. Compared with intrinsic signal imaging in the same mice, fluorescence imaging showed faster responses with ∼10 times larger signal changes. Retinotopic maps in the primary visual cortex and area LM were constructed using fluorescence imaging. After monocular deprivation (MD) of 4 d starting from postnatal day 28 (P28), deprived eye responses were suppressed compared with nondeprived eye responses in the binocular zone but not in the monocular zone. Imaging faithfully recapitulated a critical period for plasticity with maximal effects of MD observed around P28 and not in adulthood even under urethane anesthesia. Visual responses were compared before and after MD in the same mice, in which the skull was covered with clear acrylic dental resin. Deprived eye responses decreased after MD, whereas nondeprived eye responses increased. Effects of MD during a critical period were tested 2 weeks after reopening of the deprived eye. Significant ocular dominance plasticity was observed in responses elicited by moving grating patterns, but no long-lasting effect was found in visual responses elicited by light-emitting diode light stimuli. The present results indicate that transcranial flavoprotein fluorescence imaging is a powerful tool for investigating experience-dependent plasticity in the mouse visual cortex.
Blocking Memory Reconsolidation Reverses Memory-Associated Changes in Glutamate Receptor Expression
Authors: Rose Jacqueline K. , Rankin Catharine H.
Published: November 2006

It has been reported that consolidated memories can return to a labile state when reactivated and undergo a process of re-storage, termed reconsolidation, required for later recall. We investigated memory for a nonassociative learning task (habituation) and found that memory for this task also undergoes reconsolidation after recall. To investigate reconsolidation, we first demonstrated that adultCaenorhabditis elegansare capable of reliable memory 48 h after habituation training (p< 0.05). When heat shock was administered immediately after a reminder, response magnitudes of trained animals matched response levels of untrained animals: the inhibitory effects of heat shock on protein synthesis disrupted memory reconsolidation. Pharmacological blockade of non-NMDA-type glutamate receptors during reminder also eliminated 48 h retention. When expression levels of a specific glutamate receptor subunit (GLR-1) (40% homology to mammalian AMPA-type glutamate receptors) (Hart et al., 1995; Maricq et al., 1995) were measured 48 h after training, there was a significant decrease in trained compared with untrained controls. If trained worms were given a reminder followed immediately by heat shock, the effect of training on GLR-1 levels was reversed. From these studies, we conclude that both the behavioral expression of long-term memory for habituation and a cellular correlate of that memory (the alteration in expression levels of GLR-1) inC. eleganscan be altered after retrieval. Furthermore, conditions that impair memory consolidation similarly disrupt memory reconsolidation, suggesting that similar mechanisms are involved.
Amyotrophic Lateral Sclerosis 2-Deficiency Leads to Neuronal Degeneration in Amyotrophic Lateral Sclerosis through Altered AMPA Receptor Trafficking
Authors: Lai Chen , Xie Chengsong , McCormack Stefanie G. , Chiang Hsueh-Cheng , Michalak Marta K. , Lin Xian , Chandran Jayanth , Shim Hoon , Shimoji Mika , Cookson Mark R. , Huganir Richard L. , Rothstein Jeffrey D. , Price Donald L. , Wong Philip C. , Martin Lee J. , Zhu J. Julius , Cai Huaibin
Published: November 2006

Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disease is caused by a selective loss of motor neurons. One form of juvenile onset autosomal recessive ALS (ALS2) has been linked to the loss of function of theALS2gene. The pathogenic mechanism ofALS2-deficiency, however, remains unclear. To further understand the function of alsin that is encoded by the full-lengthALS2gene, we screened proteins interacting with alsin. Here, we report that alsin interacted with glutamate receptor interacting protein 1 (GRIP1) bothin vitroandin vivo, and colocalized with GRIP1 in neurons. In support of the physiological interaction between alsin and GRIP1, the subcellular distribution of GRIP1 was altered inALS2−/−spinal motor neurons, which correlates with a significant reduction of AMPA-type glutamate receptor subunit 2 (GluR2) at the synaptic/cell surface ofALS2−/−neurons. The decrease of calcium-impermeable GluR2-containing AMPA receptors at the cell/synaptic surface renderedALS2−/−neurons more susceptible to glutamate receptor-mediated neurotoxicity. Our findings reveal a novel function of alsin in AMPA receptor trafficking and provide a novel pathogenic link betweenALS2-deficiency and motor neuron degeneration, suggesting a protective role of alsin in maintaining the survival of motor neurons.
Early and Rapid Engraftment of Bone Marrow-Derived Microglia in Scrapie
Authors: Priller Josef , Prinz Marco , Heikenwalder Mathias , Zeller Nicolas , Schwarz Petra , Heppner Frank L. , Aguzzi Adriano
Published: November 2006

Prion neuroinvasion is accompanied by maximal activation of microglia, the significance of which for pathogenesis is unknown. Here, we used bone marrow (BM) cells expressing GFP (green fluorescent protein) to study the turnover of microglia in mouse scrapie. We found that ≥50% of all brain microglia were replaced by BM-derived cells before clinical disease onset. In terminally sick mice, microglia density increased threefold to fourfold. Hence BM-derived microglia rapidly and efficaciously colonize the brain in scrapie. Whereas reconstitution of wild-type mice with prion protein-deficient (Prnpo/o) BM did not alter scrapie pathogenesis,Prnpo/omice transplanted with wild-type BM cells were resistant to peripherally administered prions despite high levels of infectivity in the spleen. Cerebellar homogenates from prion-inoculatedPrnpo/omice reconstituted with >10% of wild-type microglia failed to infect transgenic mice overexpressing the cellular prion protein. Hence, in contrast to previous reports, microglia are not competent for efficient prion transport and replicationin vivo.
Neural Cell Adhesion Molecule L1-Transfected Embryonic Stem Cells Promote Functional Recovery after Excitotoxic Lesion of the Mouse Striatum
Authors: Bernreuther Christian , Dihné Marcel , Johann Verena , Schiefer Johannes , Cui Yifang , Hargus Gunnar , Schmid Janinne Sylvie , Xu Jinchong , Kosinski Christoph M. , Schachner Melitta
Published: November 2006

We have generated a murine embryonic stem cell line constitutively expressing L1 at all stages of neural differentiation to investigate the effects of L1 overexpression on stem cell proliferation, migration, differentiation, cell death, and ability to influence drug-induced rotation behavior in an animal model of Huntington's disease. L1-transfected cells showed decreased cell proliferationin vitro, enhanced neuronal differentiationin vitroandin vivo, and decreased astrocytic differentiationin vivowithout influencing cell death compared with nontransfected cells. L1 overexpression also resulted in an increased yield of GABAergic neurons and enhanced migration of embryonic stem cell-derived neural precursor cells into the lesioned striatum. Mice grafted with L1-transfected cells showed recovery in rotation behavior 1 and 4 weeks, but not 8 weeks, after transplantation compared with mice that had received nontransfected cells, thus demonstrating for the first time that a recognition molecule is capable of improving functional recovery during the initial phase in a syngeneic transplantation paradigm.
Release of Full-Length EphB2 Receptors from Hippocampal Neurons to Cocultured Glial Cells
Authors: Lauterbach Jenny , Klein Rüdiger
Published: November 2006

Glial cells are known to actively participate in neuronal development by shaping neuronal connections through axon pruning and by controlling dendritic spine morphology. These functions may in part be mediated by engulfment of neuronal structures and trans-endocytosis of neuronal material into glial cells. These processes are not well understood, and the molecular components that mediate these events have primarily been elusive. Here, we implicate the Eph/ephrin signaling system in trans-endocytosis events at the neuron-to-glia interface. Using time-lapse microscopy, we show that hippocampal neurons exogenously expressing EphB2 receptors release or pinch-off EphB2-containing vesicles at sites of neuron-to-glia contact. Cocultured glial cells endogenously express the corresponding ephrinB ligands and are able to trans-endocytose full-length EphB2 from neighboring cells. Although Eph/ephrin signaling often occurs in a bidirectional manner, the observed vesicle release from neurons to glia was only observed in a unidirectional manner, i.e., when the neurons expressed EphB2, but not ephrinBs. These findings suggest that Eph/ephrin signaling is involved in the glial cell-mediated fine sculpting of neuronal structures.
Cue-Invariant Networks for Figure and Background Processing in Human Visual Cortex
Authors: Appelbaum L. Gregory , Wade Alex R. , Vildavski Vladimir Y. , Pettet Mark W. , Norcia Anthony M.
Published: November 2006

Lateral occipital cortical areas are involved in the perception of objects, but it is not clear how these areas interact with first tier visual areas. Using synthetic images portraying a simple texture-defined figure and an electrophysiological paradigm that allows us to monitor cortical responses to figure and background regions separately, we found distinct neuronal networks responsible for the processing of each region. The figure region of our displays was tagged with one temporal frequency (3.0 Hz) and the background region with another (3.6 Hz). Spectral analysis was used to separate the responses to the two regions during their simultaneous presentation. Distributed source reconstructions were made by using the minimum norm method, and cortical current density was measured in a set of visual areas defined on retinotopic and functional criteria with the use of functional magnetic resonance imaging. The results of the main experiments, combined with a set of control experiments, indicate that the figure region, but not the background, was routed preferentially to lateral cortex. A separate network extending from first tier through more dorsal areas responded preferentially to the background region. The figure-related responses were mostly invariant with respect to the texture types used to define the figure, did not depend on its spatial location or size, and mostly were unaffected by attentional instructions. Because of the emergent nature of a segmented figure in our displays, feedback from higher cortical areas is a likely candidate for the selection mechanism by which the figure region is routed to lateral occipital cortex.
Properties of Somatosensory Synaptic Integration in Cerebellar Granule CellsIn Vivo
Authors: Jörntell Henrik , Ekerot Carl-Fredrik
Published: November 2006

In decerebrated, nonanesthetized cats, we made intracellular whole-cell recordings and extracellular cell-attached recordings from granule cells in the cerebellar C3 zone. Spontaneous EPSPs had large, relatively constant peak amplitudes, whereas IPSPs were small and did not appear to contribute substantially to synaptic integration at a short time scale. In many cases, the EPSPs of individual mossy fiber synapses appeared to be separable by their peak amplitudes. A substantial proportion of our granule cells had small receptive fields on the forelimb skin. Skin stimulation evoked explosive responses in which the constituent EPSPs were analyzed. In the rising phase of the response, our analyses indicated a participation of three to four different mossy fiber synapses, corresponding to the total number of mossy fiber afferents. The cutaneous receptive fields of the driven EPSPs overlapped, indicating an absence of convergence of mossy fibers activated from different receptive fields. Also in granule cells activated by joint movements did we find indications that different afferents were driven by the same type of input. Regardless of input type, the temporal patterns of granule cell spike activity, both spontaneous and evoked, appeared to primarily follow the activity in the presynaptic mossy fibers, although much of the nonsynchronized mossy fiber input was filtered out. In contrast to the prevailing theories of granule cell function, our results suggest a function of granule cells as signal-to-noise enhancing threshold elements, rather than as sparse coding pattern discriminators or temporal pattern generators.
Cell Migration along the Lateral Cortical Stream to the Developing Basal Telencephalic Limbic System
Authors: Carney Rosalind S. E. , Alfonso Teresa B. , Cohen Daniela , Dai Haining , Nery Susana , Stoica Bogdan , Slotkin Jonathan , Bregman Barbara S. , Fishell Gord , Corbin Joshua G.
Published: November 2006

During embryogenesis, the lateral cortical stream (LCS) emerges from the corticostriatal border (CSB), the boundary between the developing cerebral cortex and striatum. The LCS is comprised of a mix of pallial- and subpallial-derived neural progenitor cells that migrate to the developing structures of the basal telencephalon, most notably the piriform cortex and amygdala. Using a combination ofin vitroandin vivoapproaches, we analyzed the timing, composition, migratory modes, origin, and requirement of the homeodomain-containing transcription factorGsh2(genomic screened homeobox 2) in the development of this prominent migratory stream. We reveal that Pax6 (paired box gene 6)-positive pallial-derived and Dlx2 (distal-less homeobox 2)-positive subpallial-derived subpopulations of LCS cells are generated in distinct temporal windows during embryogenesis. Furthermore, our data indicate the CSB border not only is comprised of separate populations of pallial- and subpallial-derived progenitors that contribute to the LCS but also a subpopulation of cells coexpressing Pax6 and Dlx2. Moreover, despite migrating along a route outlined by a cascade of radial glia, the Dlx2-positive population appears to migrate primarily in an apparent chain-like manner, with LCS migratory cells being generated locally at the CSB with little contribution from other subpallial structures such as the medial, lateral, or caudal ganglionic eminences. We further demonstrate that the generation of the LCS is dependent on the homeodomain-containing geneGsh2, revealing a novel requirement forGsh2in telencephalic development.
Enhancing Cognition after Stress with Gene Therapy
Authors: Nicholas Andrea , Munhoz Carolina D. , Ferguson Deveroux , Campbell Laura , Sapolsky Robert
Published: November 2006

Hippocampal function is essential for the acquisition, consolidation, and retrieval of spatial memory. High circulating levels of glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, have been shown to impair both acquisition and retrieval and can either impair or enhance consolidation, depending on experimental conditions. In contrast, estrogen can enhance spatial memory performance and can block the deleterious effects of GCs on such performance. We therefore constructed a chimeric gene (“ER/GR”) containing the hormone-binding domain of the GC receptor and the DNA binding domain of the estrogen receptor; as a result, ER/GR transduces deleterious GC signals into beneficial estrogenic ones. We show here that acute immobilization stress, before acquisition and retrieval phases, increases latencies for male rats in a hidden platform version of the Morris water maze. This impairment is blocked by hippocampal expression of the ER/GR transgene. ER/GR expression also blocks decreases in platform crossings caused by acute stress, either after acquisition or before retrieval. Three days of stress before acquisition produces an estrogen-like enhancement of performance in ER/GR-treated rats. Moreover, ER/GR blocks the suppressive effects of GCs on expression of brain-derived neurotrophic factor (BDNF), a growth factor central to hippocampal-dependent cognition and plasticity, instead producing an estrogenic increase in BDNF expression. Thus, ER/GR expression enhances spatial memory performance and blocks the impairing effects of GCs on such performance.
Dynamic Spatial Processing Originates in Early Visual Pathways
Authors: Allen Elena A. , Freeman Ralph D.
Published: November 2006

A variety of studies in the visual system demonstrate that coarse spatial features are processed before those of fine detail. This aspect of visual processing is assumed to originate in striate cortex, where single cells exhibit a refinement of spatial frequency tuning over the duration of their response. However, in early visual pathways, well known temporal differences are present between center and surround components of receptive fields. Specifically, response latency of the receptive field center is relatively shorter than that of the surround. This spatiotemporal inseparability could provide the basis of coarse-to-fine dynamics in early and subsequent visual areas. We have investigated this possibility with three separate approaches. First, we predict spatial-frequency tuning dynamics from the spatiotemporal receptive fields of 118 cells in the lateral geniculate nucleus (LGN). Second, we compare these linear predictions to measurements of tuning dynamics obtained with a subspace reverse correlation technique. We find that tuning evolves dramatically in thalamic cells, and that tuning changes are generally consistent with the temporal differences between spatiotemporal receptive field components. Third, we use a model to examine how different sources of dynamic input from early visual pathways can affect tuning in cortical cells. We identify two mechanisms capable of producing substantial dynamics at the cortical level: (1) the center-surround delay in individual LGN neurons, and (2) convergent input from multiple cells with different receptive field sizes and response latencies. Overall, our simulations suggest that coarse-to-fine tuning in the visual cortex can be generated completely by a feedforward process.
Enhancement of Vision by Monocular Deprivation in Adult Mice
Authors: Prusky Glen T. , Alam Nazia M. , Douglas Robert M.
Published: November 2006

Plasticity of vision mediated through binocular interactions has been reported in mammals only during a “critical” period in juvenile life, wherein monocular deprivation (MD) causes an enduring loss of visual acuity (amblyopia) selectively through the deprived eye. Here, we report a different form of interocular plasticity of vision in adult mice in which MD leads to an enhancement of the optokinetic response (OKR) selectively through the nondeprived eye. Over 5 d of MD, the spatial frequency sensitivity of the OKR increased gradually, reaching a plateau of ∼36% above pre-deprivation baseline. Eye opening initiated a gradual decline, but sensitivity was maintained above pre-deprivation baseline for 5–6 d. Enhanced function was restricted to the monocular visual field, notwithstanding the dependence of the plasticity on binocular interactions. Activity in visual cortex ipsilateral to the deprived eye was necessary for the characteristic induction of the enhancement, and activity in visual cortex contralateral to the deprived eye was necessary for its maintenance after MD. The plasticity also displayed distinct learning-like properties: Active testing experience was required to attain maximal enhancement and for enhancement to persist after MD, and the duration of enhanced sensitivity after MD was extended by increasing the length of MD, and by repeating MD. These data show that the adult mouse visual system maintains a form of experience-dependent plasticity in which the visual cortex can modulate the normal function of subcortical visual pathways.
Directional Signals in the Prefrontal Cortex and in Area MT during a Working Memory for Visual Motion Task
Authors: Zaksas Daniel , Pasternak Tatiana
Published: November 2006

Neurons in the middle temporal visual area (MT) have been implicated in the perception of visual motion, whereas prefrontal cortex (PFC) neurons have been linked to temporary storage of sensory signals, attentional and executive control of behavior. Using a task that placed demands on both sets of neurons, we investigated their contribution to working memory for visual motion. Monkeys compared the direction of two moving random-dot stimuli, sample and test, separated by a brief memory delay. Neurons in both areas showed robust direction-selective activity during all phases of the task. During the sample, ∼60% of task-related PFC neurons were direction selective, and this selectivity emerged 40 ms later than in MT. Unlike MT, the PFC responses to sample did not correlate with behavioral choices, but their selectivity was modulated by task demands and diminished on error trials. Reliable directional signals were found in both areas during the memory delay, but these signals were transient rather than sustained by neurons of either area. Responses to the test in both areas were modulated by the remembered sample direction, decreasing when the test direction matched the sample. This decrease arose in the PFC 100 ms later than in MT and was predictive of the forthcoming decision. Our data suggest that neurons in the two regions are functionally connected and make unique contributions to different task components. PFC neurons reflect task-related information about visual motion and represent decisions that may be based, in part, on the comparison in MT between the remembered sample and test.