An infrastructure for secure data sharing: a clinical data implementation.

Objective: To address database interoperability challenges to improve collaboration among disparate organizations. Materials and Methods: We developed a lightweight system to allow broad but well-controlled data sharing while preserving local data protection policies. We used 2 NIST-developed technologies-Next-generation Database Access Control (NDAC) and the Data Block Matrix (DBM)-to create a proof-of-concept system called the Secure Federated Data Sharing System (SFDS). NDAC controls access to database resources down to the field level based on attributes assigned to users. The DBM manages and shares authoritative user-attribute assignments across a federation of organizations, implemented using a modified open-source permissioned blockchain, to manage and share authoritative user-attribute assignments across a federation of organizations. We used synthetic data to demonstrate a clinical research data-sharing use case using the SFDS. Results: We demonstrated, through consent, the onboarding of previously unknown users into NDAC via assignments to their DBM-validated attributes, allowing those users policy-preserving access to local database resources. The SFDS main system components-NDAC and DBM-also showed excellent performance metrics. Discussion: The SFDS provides a generic data-sharing infrastructure that effectively and securely achieves data-sharing objectives. It is completely transparent to the otherwise normal business operations of participating organizations. It requires no changes to database management systems or existing methods of authenticating and authorizing local user access to local resources. Conclusion: This efficiency, flexibility of deployment, and granularity of control make this new infrastructure solution practical for meeting the data-sharing and protection objectives of the clinical research community.

Optimized 13C-TrEnDi Enhances the Sensitivity of Plasmenyl Ether Glycerophospholipids and Demonstrates Compatibility with Other Derivatization Strategies.

The identification and quantitation of plasmalogen glycerophospholipids is challenging due to their isobaric overlap with plasmanyl ether-linked glycerophospholipids, susceptibility to acid degradation, and their typically low abundance in biological samples. Trimethylation enhancement using diazomethane (TrEnDi) can be used to significantly enhance the signal of glycerophospholipids through the creation of quaternary ammonium groups producing fixed positive charges using 13C-diazomethane in complex lipid extracts. Although TrEnDi requires a strong acid for complete methylation, we report an optimized protocol using 10 mM HBF4 with the subsequent addition of a buffer solution that prevents acidic hydrolysis of plasmalogen species and enables the benefits of TrEnDi to be realized for this class of lipids. These optimized conditions were applied to aliquots of bovine liver extract (BLE) to achieve permethylation of plasmalogen lipids within a complex mixture. Treating aliquots of unmodified and TrEnDi-derivatized BLE samples with 80% formic acid and comparing their liquid chromatography mass spectrometry (LCMS) results to analogous samples not treated with formic acid, enabled the identification of 29 plasmalogen species. On average, methylated plasmalogen species from BLE demonstrated 2.81-fold and 28.1-fold sensitivity gains over unmodified counterparts for phosphatidylcholine and phosphatidylethanolamine plasmalogen species, respectively. Furthermore, the compatibility of employing 13C-TrEnDi and a previously reported iodoacetalization strategy was demonstrated to effectively identify plasmenyl-ether lipids in complex biological extracts at greater levels of sensitivity. Overall, we detail an optimized 13C-TrEnDi derivatization strategy that enables the analysis of plasmalogen glycerophospholipids with no undesired cleavage of radyl groups, boosting their sensitivity in LCMS and LCMS/MS analyses.

Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors.

Purpose: Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BPND) in rodent PET studies. Procedures: PET and CT scans were acquired on 5 female and 5 male CD-1 mice with PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BPND in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT. Results: The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BPND in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter. Conclusions: The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BPND due to erroneous estimates of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners.

An In Silico Database for Automated Feature Identification of High-Resolution Tandem Mass Spectrometry 13C-Trimethylation Enhancement Using Diazomethane (13C-TrEnDi)-Modified Lipid Data.

13C-Trimethylation enhancement using diazomethane (13C-TrEnDi) is a chemical derivatization technique that uses 13C-labeled diazomethane to increase mass spectrometry (MS) signal intensities for phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipid classes, both of which are of major interest in biochemistry. In silico mass spectrometry databases have become mainstays in lipidomics experiments; however, 13C-TrEnDi-modified PC and PE species have altered m/z and fragmentation patterns from their native counterparts. To build a database of 13C-TrEnDi-modified PC and PE species, a lipid extract from nutritional yeast was derivatized and fragmentation spectra of modified PC and PE species were mined using diagnostic fragmentation filtering by searching 13C-TrEnDi-modified headgroups with m/z 199 (PC) and 202 (PE). Identities of 25 PC and 10 PE species were assigned after comparing to predicted masses from the Lipid Maps Structure Database with no false positive identifications observed; neutral lipids could still be annotated after derivatization. Collision energies from 16 to 52 eV were examined, resulting in three additional class-specific fragment ions emerging, as well as a combined sn-1/sn-2 fragment ion, allowing sum-composition level annotations to be assigned. Using the Lipid Blast templates, a NIST-compatible 13C-TrEnDi database was produced based on fragmentation spectra observed at 36 eV and tested on HEK 293T cell lipid extracts, identifying 47 PC and 24 PE species, representing a 1.8-fold and 2.2-fold increase in annotations, respectively. The 13C-TrEnDi database is freely available, MS vendor-independent, and widely compatible with MS data processing pipelines, increasing the throughput and accessibility of TrEnDi for lipidomics applications.

Minimizing prescribing errors: A phenomenological exploration of the views and experiences of independent prescribing pharmacists.

AIMS: This study aims to explore the views and experiences of independent prescribing (IP) pharmacists regarding prescribing errors and strategies to mitigate errors in practice. METHODS: One-to-one online semi-structured interviews were conducted with IP pharmacists across the United Kingdom. Verbatim transcripts of the interview were generated and coded using NVivo® 12 software for thematic analysis. A mixed inductive and deductive approach was used to generate themes and sub-themes which were then mapped onto the framework of factors that influence clinical practice proposed by Vincent et al. RESULTS: A total of 14 interviews were conducted. Participants linked the risk-averse nature of a pharmacist, self-perception of their roles as medicines experts, and previous experience of keeping checks on doctors' prescriptions as a dispenser often made them feel confident in prescribing. However, lacking adequate diagnostic skills, inadequate prescribing training programmes, and dealing with complex patients often made them feel vulnerable to committing errors. Organizational and system-related factors such as work interruptions and increased workload were identified as other factors linked to prescribing errors. CONCLUSIONS: Independent prescribing pharmacists use a variety of strategies to reduce the risk of prescribing errors. Promoting diagnostic competency in their area of practice, strengthening undergraduate and prescribing curricula, and addressing known organizational and system-related factors linked to prescribing errors can minimize errors and promote patient safety.

It's time to talk fathers: The impact of paternal depression on parenting style and child development during the COVID-19 pandemic.

This study aimed to understand the relationship between paternal depression, parenting behavior and child developmental outcomes during the SARS-CoV-2 (COVID) pandemic. In addition, the paternal experience of the pandemic, such as the impact of lockdowns, was explored. Fathers of children aged 6-11 years old (n = 87) were recruited for an online cross-sectional survey. Data was collected through questionnaires and open-ended comments. Regression analysis indicated a higher level of self-reported depressive symptomology in fathers more severely impacted by the pandemic across financial, familial and health domains. Further, COVID-19 impact, but not paternal depression, was linked to fewer authoritative parenting behaviors, characterized as lower warmth and responsiveness. Paternal pandemic impact and depression symptoms were independently predictive of child cognitive scores, and both were associated with emotional and behavioral outcomes. A content analysis of open-ended responses from fathers noted that concerns for their children, work and mental health were most prevalent during the pandemic. However, several responders also reported no change or positive facets of lockdowns related to the pandemic. These finds are discussed in the context of a possible behavioural mechanism of action accounting for the effect of these factors on child development. Clinical implications include targeted interventions for at risk groups as well as psychoeducation for fathers that acknowledge difference in paternal coping and support seeking.

Seasonal changes in membrane structure and excitability in retinal neurons of goldfish (Carassius auratus) under constant environmental conditions.

Seasonal modifications in the structure of cellular membranes occur as an adaptive measure to withstand exposure to prolonged environmental change. Little is known about whether such changes occur independently of external cues, such as photoperiod or temperature, or how they may impact the central nervous system. We compared membrane properties of neurons isolated from the retina of goldfish (Carassius auratus), an organism well adapted to extreme environmental change, during the summer and winter months. Goldfish were maintained in a facility under constant environmental conditions throughout the year. Analysis of whole-retina phospholipid composition using mass spectrometry-based lipidomics revealed a twofold increase in phosphatidylethanolamine species during the winter, suggesting an increase in cell membrane fluidity. Atomic force microscopy was used to produce localized, nanoscale-force deformation of neuronal membranes. Measurement of Young's modulus indicated increased membrane-cortical stiffness (or decreased elasticity) in neurons isolated during the winter. Voltage-clamp electrophysiology was used to assess physiological changes in neurons between seasons. Winter neurons displayed a hyperpolarized reversal potential (Vrev) and a significantly lower input resistance (Rin) compared with summer neurons. This was indicative of a decrease in membrane excitability during the winter. Subsequent measurement of intracellular Ca2+ activity using Fura-2 microspectrofluorometry confirmed a reduction in action potential activity, including duration and action potential profile, in neurons isolated during the winter. These studies demonstrate chemical and biophysical changes that occur in retinal neurons of goldfish throughout the year without exposure to seasonal cues, and suggest a novel mechanism of seasonal regulation of retinal activity.

Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.

Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circuit of aged, learning-impaired animals is well-documented, its neurobiological substrates remain elusive. Here we show that the synaptic architecture of hippocampal regions CA1 and CA3 is maintained in a young adult-like state in aged rats that performed comparably to their young adult counterparts in both trace eyeblink conditioning and Morris water maze learning. In contrast, among learning-impaired, but equally aged rats, we found that a redistribution of synaptic weights amplifies the influence of autoassociational connections among CA3 pyramidal neurons, yet reduces the synaptic input onto these same neurons from the dentate gyrus. Notably, synapses within hippocampal region CA1 showed no group differences regardless of cognitive ability. Taking the data together, we find the imbalanced synaptic weights within hippocampal CA3 provide a substrate that can explain the abnormal firing characteristics of both CA3 and CA1 pyramidal neurons in aged, learning-impaired rats. Furthermore, our work provides some clarity with regard to how some animals cognitively age successfully, while others' lifespans outlast their "mindspans."

iTrEnDi: In Situ Trimethylation Enhancement Using Diazomethane: Improved and Expanded Glycerophospholipid and Sphingolipid Analyses via a Microscale Autonomous Derivatization Platform.

Trimethylation enhancement using diazomethane (TrEnDi) is a derivatization technique that significantly enhances the signal intensity of glycerophospholipid species in mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses. Here, we describe a novel apparatus that is able to conduct in situ TrEnDi (iTrEnDi) by generating and immediately reacting small amounts of gaseous diazoalkane with analyte molecules. iTrEnDi allows complete and rapid methylation of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and sphingomyelin (SM) in a safe manner by removing any need for direct handling of dangerous diazoalkane solutions. iTrEnDi-modified PC ([PCTr]+) and PE ([PETr]+) showed similar sensitivity enhancements and fragmentation patterns compared to our previously reported methodology. iTrEnDi yielded dimethylated PA ([PATr]), which exhibited dramatically improved chromatographic behavior and a 14-fold increase in liquid chromatography MS (LCMS) sensitivity compared to unmodified PA. In comparison to in-solution-based TrEnDi, iTrEnDi demonstrated a modest decrease in sensitivity, likely due to analyte losses during handling. However, the enhanced safety benefits of iTrEnDi coupled with its ease of use and capacity for automation, as well as its accommodation of more-reactive diazoalkane species, vastly improve the accessibility and utility of this derivatization technique. Finally, as a proof of concept, iTrEnDi was used to produce diazoethane (DZE), a more-reactive diazoalkane than diazomethane. Reaction between DZE and PC yielded ethylated [PCTr]+, which fragmented via MS/MS to produce a high-intensity characteristic fragment ion, enabling a novel and highly sensitive precursor ion scan.

Human Cortical Serotonin 2A Receptor Occupancy by Psilocybin Measured Using [11C]MDL 100,907 Dynamic PET and a Resting-State fMRI-Based Brain Parcellation.

Psilocybin (a serotonin 2A, or 5-HT2A, receptor agonist) has shown preliminary efficacy as a treatment for mood and substance use disorders. The current report utilized positron emission tomography (PET) with the selective 5-HT2A receptor inverse agonist radioligand [11C]MDL 100,907 (a.k.a. M100,907) and cortical regions of interest (ROIs) derived from resting-state functional connectivity-based brain parcellations in 4 healthy volunteers (2 females) to determine regional occupancy/target engagement of 5-HT2A receptors after oral administration of a psychoactive dose of psilocybin (10 mg/70 kg). Average 5-HT2A receptor occupancy across all ROIs was 39.5% (± 10.9% SD). Three of the ROIs with greatest occupancy (between 63.12 and 74.72% occupancy) were within the default mode network (subgenual anterior cingulate and bilateral angular gyri). However, marked individual variability in regional occupancy was observed across individuals. These data support further investigation of the relationship between individual differences in the acute and enduring effects of psilocybin and the degree of regional 5-HT2A receptor occupancy.

Reducing Compassion Fatigue in Inpatient Pediatric Oncology Nurses.

OBJECTIVES: To develop an evidence-based compassion fatigue program and evaluate its impact on nurse-reported burnout, secondary traumatic stress, and compassion satisfaction, as well as correlated factors of resilience and coping behaviors. SAMPLE & SETTING: The quality improvement pilot program was conducted with 59 nurses on a 20-bed subspecialty pediatric oncology unit at the St. Jude Children's Research Hospital in Memphis, Tennessee. METHODS & VARIABLES: Validated measures of compassion fatigue and satisfaction (Professional Quality of Life Scale V [ProQOLV]), coping (Brief COPE), and resilience (Connor-Davidson Resilience Scale-2) were evaluated preprogram and at two, four, and six months postprogram, with resilience and coping style measured at baseline and at six months postprogram. RESULTS: Secondary traumatic stress scores significantly improved from baseline to four months. Select coping characteristics were significantly correlated with ProQOLV subscale scores. IMPLICATIONS FOR NURSING: Ongoing organizational support and intervention can reduce compassion fatigue and foster compassion satisfaction among pediatric oncology nurses.

Evaluation of 18F-RO-948 PET for Quantitative Assessment of Tau Accumulation in the Human Brain.

The availability of tau PET radioligands enables quantitative assessment of tau density and distribution in the human brain. We evaluated the kinetics of a novel radioligand, 18F-RO-948 (previously referred to as 18F-RO6958948), and its ability to identify tau positivity in individual patients with mild Alzheimer disease (AD). Methods: Eleven subjects with amyloid-positive mild AD, 5 amyloid-negative older control subjects (OC), and 5 younger control subjects (YC) completed 1 or 2 (4 AD and 5 OC) PET scans with 18F-RO-948 for 90, 120, or 200 min. The kinetics of the radioligand was evaluated with standard compartmental and noncompartmental models (with plasma data in 70% of cases), tissue-reference methods, and SUV ratio. These approaches were applied to assess the ability of 18F-RO-948 to discriminate AD subjects from OC subjects. Results: The plasma reference graphical analysis appeared to be the optimal method of quantification for 18F-RO-948, yielding strictly time-consistent values of distribution volume and distribution volume ratio at 90 min against the analyses at 120 and 200 min. The reference tissue graphical analysis and SUV ratio were cross-validated against plasma reference graphical analysis. Test-retest evaluation showed excellent reproducibility. A proposed novel index of tau load, the regional tau-positive fraction, showed high values in the medial and lateral temporal and parietal regions in AD and successfully separated AD subjects from OC and YC subjects with a significant margin. Conclusion:18F-RO-948 appears to be a promising radioligand for quantitative imaging of tau in the brain of AD patients.

Brain PET Imaging of α7-nAChR with [18F]ASEM: Reproducibility, Occupancy, Receptor Density, and Changes in Schizophrenia.

Background: The α7 nicotinic acetylcholine receptor increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7 nicotinic acetylcholine receptor suggests a role in cognition. Methods: We expanded the first-in-human PET imaging of α7 nicotinic acetylcholine receptor with [18F]ASEM from 5 to 21 healthy nonsmoking volunteers and added a feasibility study in 6 male patients with schizophrenia. Study aims included: (1) confirmation of test-retest reproducibility of [18F]ASEM binding, (2) demonstration of specificity by competition with DMXB-A, an α7 nicotinic acetylcholine receptor partial agonist, (3) estimation of [18F]ASEM binding potentials and α7 nicotinic acetylcholine receptor density in vivo in humans, and (4) demonstrating the feasibility of studying α7 nicotinic acetylcholine receptor as a target for schizophrenia. Results: Test-retest PET confirmed reproducibility (>90%) (variability ≤7%) of [18F]ASEM volume of distribution (VT) estimates in healthy volunteers. Repeated sessions of PET in 5 healthy subjects included baseline and effect of inhibition after oral administration of 150 mg DMXB-A. From reduction of binding potentials, we estimated the dose-dependent occupancy of α7 nicotinic acetylcholine receptor by DMXB-A at 17% to 49% for plasma concentrations at 60 to 200 nM DMXB-A. In agreement with evidence postmortem, α7 nicotinic acetylcholine receptor density averaged 0.67 to 0.82 nM and inhibitor affinity constant averaged 170 to 385 nM. Median VT in a feasibility study of 6 patients with schizophrenia was lower than in healthy volunteers in cingulate cortex, frontal cortex, and hippocampus (P = 0.02, corrected for multiple comparions, Mann-Whitney test). Conclusions: The current results confirm the reproducibility of [18F]ASEM VT estimates and the specificity of the tracer for α7 nicotinic acetylcholine receptor. Preliminary findings from our feasibility study of [18F]ASEM binding in patients with schizophrenia are suggestive and provide guidance for future studies with more subjects.

Linking dopaminergic reward signals to the development of attentional bias: A positron emission tomographic study.

The attention system is shaped by reward history, such that learned reward cues involuntarily draw attention. Recent research has begun to uncover the neural mechanisms by which learned reward cues compete for attention, implicating dopamine (DA) signaling within the dorsal striatum. How these elevated priority signals develop in the brain during the course of learning is less well understood, as is the relationship between value-based attention and the experience of reward during learning. We hypothesized that the magnitude of the striatal DA response to reward during learning contributes to the development of a learned attentional bias towards the cue that predicted it, and examined this hypothesis using positron emission tomography with [11C]raclopride. We measured changes in dopamine release for rewarded versus unrewarded visual search for color-defined targets as indicated by the density and distribution of the available D2/D3 receptors. We then tested for correlations of individual differences in this measure of reward-related DA release to individual differences in the degree to which previously reward-associated but currently task-irrelevant stimuli impair performance in an attention task (i.e., value-driven attentional bias), revealing a significant relationship in the right anterior caudate. The degree to which reward-related DA release was right hemisphere lateralized was also predictive of later attentional bias. Our findings provide support for the hypothesis that value-driven attentional bias can be predicted from reward-related DA release during learning.

CeNDR, the Caenorhabditis elegans natural diversity resource.

Studies in model organisms have yielded considerable insights into the etiology of disease and our understanding of evolutionary processes. Caenorhabditis elegans is among the most powerful model organisms used to understand biology. However, C. elegans is not used as extensively as other model organisms to investigate how natural variation shapes traits, especially through the use of genome-wide association (GWA) analyses. Here, we introduce a new platform, the C. elegans Natural Diversity Resource (CeNDR) to enable statistical genetics and genomics studies of C. elegans and to connect the results to human disease. CeNDR provides the research community with wild strains, genome-wide sequence and variant data for every strain, and a GWA mapping portal for studying natural variation in C. elegans Additionally, researchers outside of the C. elegans community can benefit from public mappings and integrated tools for comparative analyses. CeNDR uses several databases that are continually updated through the addition of new strains, sequencing data, and association mapping results. The CeNDR data are accessible through a freely available web portal located at http://www.elegansvariation.org or through an application programming interface.

Learning with interactive computer graphics in the undergraduate neuroscience classroom.

Instruction of neuroanatomy depends on graphical representation and extended self-study. As a consequence, computer-based learning environments that incorporate interactive graphics should facilitate instruction in this area. The present study evaluated such a system in the undergraduate neuroscience classroom. The system used the method of adaptive exploration, in which exploration in a high fidelity graphical environment is integrated with immediate testing and feedback in repeated cycles of learning. The results of this study were that students considered the graphical learning environment to be superior to typical classroom materials used for learning neuroanatomy. Students managed the frequency and duration of study, test, and feedback in an efficient and adaptive manner. For example, the number of tests taken before reaching a minimum test performance of 90 % correct closely approximated the values seen in more regimented experimental studies. There was a wide range of student opinion regarding the choice between a simpler and a more graphically compelling program for learning sectional anatomy. Course outcomes were predicted by individual differences in the use of the software that reflected general work habits of the students, such as the amount of time committed to testing. The results of this introduction into the classroom are highly encouraging for development of computer-based instruction in biomedical disciplines.

Environmental influences on neural systems of relational complexity.

Constructivist learning theory contends that we construct knowledge by experience and that environmental context influences learning. To explore this principle, we examined the cognitive process relational complexity (RC), defined as the number of visual dimensions considered during problem solving on a matrix reasoning task and a well-documented measure of mature reasoning capacity. We sought to determine how the visual environment influences RC by examining the influence of color and visual contrast on RC in a neuroimaging task. To specify the contributions of sensory demand and relational integration to reasoning, our participants performed a non-verbal matrix task comprised of color, no-color line, or black-white visual contrast conditions parametrically varied by complexity (relations 0, 1, 2). The use of matrix reasoning is ecologically valid for its psychometric relevance and for its potential to link the processing of psychophysically specific visual properties with various levels of RC during reasoning. The role of these elements is important because matrix tests assess intellectual aptitude based on these seemingly context-less exercises. This experiment is a first step toward examining the psychophysical underpinnings of performance on these types of problems. The importance of this is increased in light of recent evidence that intelligence can be linked to visual discrimination. We submit three main findings. First, color and black-white visual contrast (BWVC) add demand at a basic sensory level, but contributions from color and from BWVC are dissociable in cortex such that color engages a "reasoning heuristic" and BWVC engages a "sensory heuristic." Second, color supports contextual sense-making by boosting salience resulting in faster problem solving. Lastly, when visual complexity reaches 2-relations, color and visual contrast relinquish salience to other dimensions of problem solving.

Flexor tendon sheath as a source of pain in lesser metatarsal overload.

BACKGROUND: Lesser metatarsal overload may lead to pathologic conditions ranging from plantar metatarsophalangeal joint pain to dislocation. The flexor tendon sheath lies directly plantar to the joint. The increased pressure associated with lesser metatarsal overload may lead to synovitis and pain of the flexor tendon sheath. METHODS: Fifteen consecutive patients with lesser metatarsal overload had visual analog scale scores determined at three metatarsophalangeal joint areas to determine the source of pain. The patients underwent seven maneuvers to determine the pain scale score: single-leg heel raise and palpation of the second and third metatarsophalangeal joints on the plantar proximal, plantar distal, and dorsal aspects. The patients were then injected with 0.5 mL of lidocaine, 2%, into the second and third flexor tendon sheaths, and the maneuvers were repeated. RESULTS: Before the injection, the second metatarsophalangeal joint had a significantly greater visual analog scale score plantar than dorsal (6.9 and 2.6, P < or = .01). The flexor tendon sheath injection significantly improved all seven pain scale scores. CONCLUSIONS: Patients with lesser metatarsal overload experienced significantly greater visual analog scale pain scores on the plantar than the dorsal aspect of the second metatarsophalangeal joint. The scores significantly improved after diagnostic injection in the flexor tendon sheaths. The flexor tendon sheaths are probably involved in patients with primarily plantar pain.