White matter microstructural abnormalities in blast-exposed combat veterans: accounting for potential pre-injury factors using consanguineous controls.

PURPOSE: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. METHODS: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. RESULTS: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. CONCLUSIONS: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

COVID-19 Neuroimaging Update: Pathophysiology, Acute Findings, and Post-Acute Developments.

COVID-19 has prominent effects on the nervous system with important manifestations on neuroimaging. In this review, we discuss the neuroimaging appearance of acute COVID-19 that became evident during the early stages of the pandemic. We highlight the underlying pathophysiology mediating nervous system effects and neuroimaging appearances including systemic inflammatory response such as cytokine storm, coagulopathy, and para/post-infections immune mediated phenomena. We also discuss the nervous system manifestations of COVID-19 and the role of imaging as the pandemic has evolved over time, including related to the development of vaccines and the emergence of post-acute sequalae such as long COVID.

Trans-synaptic EphB2-ephrin-B3 interaction regulates excitatory synapse density by inhibition of postsynaptic MAPK signaling.

Nervous system function requires tight control over the number of synapses individual neurons receive, but the underlying cellular and molecular mechanisms that regulate synapse number remain obscure. Here we present evidence that a trans-synaptic interaction between EphB2 in the presynaptic compartment and ephrin-B3 in the postsynaptic compartment regulates synapse density and the formation of dendritic spines. Observations in cultured cortical neurons demonstrate that synapse density scales with ephrin-B3 expression level and is controlled by ephrin-B3-dependent competitive cell-cell interactions. RNA interference and biochemical experiments support the model that ephrin-B3 regulates synapse density by directly binding to Erk1/2 to inhibit postsynaptic Ras/mitogen-activated protein kinase signaling. Together these findings define a mechanism that contributes to synapse maturation and controls the number of excitatory synaptic inputs received by individual neurons.

Health Systems Science - A Primer for Radiologists.

Health systems science (HSS) is an educational framework designed to promote improved care through enhanced citizenship and the training of systems-fluent individuals trained in the science of health care delivery.  HSS education in residency builds upon foundations established during medical school, emphasizing practical skills development, and fostering a growth mindset among trainees.  The HSS framework organizes elements of system-based practice for radiology trainees, promoting practice-readiness for providing safe, timely, effective, efficient, equitable and patient centered radiological care. This paper serves as a primer for radiologists to understand and apply the HSS framework. Additionally, we highlight radiology-specific curricular elements aligned with the HSS framework, and provide teaching resources both for classroom education and for resident self-study.

Healthcare resilience: a meta-narrative systematic review and synthesis of reviews.

OBJECTIVES: The COVID-19 pandemic has tested global healthcare resilience. Many countries previously considered 'resilient' have performed poorly. Available organisational and system frameworks tend to be context-dependent and focus heavily on physical capacities. This study aims to explore and synthesise evidence about healthcare resilience and present a unified framework for future resilience-building. DESIGN: Systematic review and synthesis of reviews using a meta-narrative approach. SETTING: Healthcare organisations and systems. PRIMARY AND SECONDARY OUTCOME MEASURES: Definitions, concepts and measures of healthcare resilience. We used thematic analysis across included reviews to summarise evidence on healthcare resilience. RESULTS: The main paradigms within healthcare resilience include global health, disaster risk reduction, emergency management, patient safety and public health. Definitions of healthcare resilience recognise various hierarchical levels: individual (micro), facility or organisation (meso), health system (macro) and planetary or international (meta). There has been a shift from a focus on mainly disasters and crises, to an 'all-hazards' approach to resilience. Attempts to measure resilience have met with limited success. We analysed key concepts to build a framework for healthcare resilience containing pre-event, intra-event, post-event and trans-event domains. Alongside, we synthesise a definition which dovetails with our framework. CONCLUSION: Resilience increasingly takes an all-hazards approach and a process-oriented perspective. There is increasing recognition of the relational aspects of resilience. Few frameworks incorporate these, and they are difficult to capture within measurement systems. We need to understand how resilience works across hierarchical levels, and how competing priorities may affect overall resilience. Understanding these will underpin interdisciplinary, cross-sectoral and multi-level approaches to healthcare resilience for the future. PROSPERO REGISTRATION NUMBER: CRD42022314729.

Ephrin-B1 and ephrin-B2 mediate EphB-dependent presynaptic development via syntenin-1.

The development of central nervous system synapses requires precise coordination between presynaptic and postsynaptic components. The EphB family controls postsynaptic development by interacting with glutamate receptors and regulating dendritic filopodia motility, but how EphBs induce the formation of presynaptic specializations is less well understood. Here, we show that knockdown of presynaptic ephrin-B1, ephrin-B2, or syntenin-1, but not ephrin-B3, prevents EphB-dependent presynaptic development. Ephrin-B1, ephrin-B2, and syntenin-1 are clustered together with presynaptic markers, suggesting that these molecules function jointly in presynaptic development. Knockdown of ephrin-B1 or ephrin-B2 reduces the number of synaptic specializations and the colocalization of syntenin-1 with synaptic markers. Simultaneous knockdown of ephrin-B1 and ephrin-B2 suggests that they function independently in the formation of synaptic contacts, but act together to recruit syntenin-1 to presynaptic terminals. Taken together, these results demonstrate that ephrin-B1 and ephrin-B2 function with EphB to mediate presynaptic development via syntenin-1.

Brain MRI findings in COVID-19 patients with PRES: A systematic review.

BACKGROUND: Numerous case reports and case series have described brain Magnetic Resonance Imaging (MRI) findings in Coronavirus disease 2019 (COVID-19) patients with concurrent posterior reversible encephalopathy syndrome (PRES). PURPOSE: We aim to compile and analyze brain MRI findings in patients with COVID-19 disease and PRES. METHODS: PubMed and Embase were searched on April 5th, 2021 using the terms "COVID-19", "PRES", "SARS-CoV-2" for peer-reviewed publications describing brain MRI findings in patients 21 years of age or older with evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and PRES. RESULTS: Twenty manuscripts were included in the analysis, which included descriptions of 30 patients. The average age was 57 years old. Twenty-four patients (80%) required mechanical ventilation. On brain MRI examinations, 15 (50%) and 7 (23%) of patients exhibited superimposed foci of hemorrhage and restricted diffusion respectively. CONCLUSIONS: PRES is a potential neurological complication of COVID-19 related disease. COVID-19 patients with PRES may exhibit similar to mildly greater rates of superimposed hemorrhage compared to non-COVID-19 PRES patients.

Review of COVID-19, part 1: Abdominal manifestations in adults and multisystem inflammatory syndrome in children.

The coronavirus disease 2019 (COVID -19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world, resulting in severe morbidity, mortality and economic hardship, and altering the landscape of healthcare forever. Although primarily a pulmonary illness, it can affect multiple organ systems throughout the body, sometimes with devastating complications and long-term sequelae. As we move into the second year of this pandemic, a better understanding of the pathophysiology of the virus and the varied imaging findings of COVID-19 in the involved organs is crucial to better manage this complex multi-organ disease and to help improve overall survival. This manuscript provides a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19 with the exception of unique cardiothoracic features associated with multisystem inflammatory syndrome in children (MIS-C). In Part I, extra-thoracic manifestations of COVID-19 in the abdomen in adults and features of MIS-C will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.

Review of COVID-19, part 2: Musculoskeletal and neuroimaging manifestations including vascular involvement of the aorta and extremities.

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world resulting in severe morbidity, mortality and economic hardship, altering the landscape of healthcare forever. Its devastating and most frequent thoracic and cardiac manifestations have been well reported since the start of the pandemic. Its extra-thoracic manifestations are myriad and understanding them is critical in diagnosis and disease management. The role of radiology is growing in the second wave and second year of the pandemic as the multiorgan manifestations of COVID-19 continue to unfold. Musculoskeletal, neurologic and vascular disease processes account for a significant number of COVID-19 complications and understanding their frequency, clinical sequelae and imaging manifestations is vital in guiding management and improving overall survival. The authors aim to provide a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19. In Part I, abdominal manifestations of COVID-19 in adults and multisystem inflammatory syndrome in children will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.

Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality. METHODS: A total of 581 hospitalized patients with confirmed SARS-CoV-2 infection, neurologic involvement, and brain imaging were compared to hospitalized non-neurologic patients with coronavirus disease 2019 (COVID-19). Four patterns of neurologic manifestations were identified: acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, preexisting comorbidities, vital signs, laboratory values, and pattern of neurologic manifestations. Significant predictors were incorporated into a disease severity score. Patients with neurologic manifestations were matched with patients of the same age and disease severity to assess the risk of death. RESULTS: A total of 4,711 patients with confirmed SARS-CoV-2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurologic issues of sufficient concern to warrant neuroimaging. These patients were compared to 1,743 non-neurologic patients with COVID-19 matched for age and disease severity admitted during the same period. Patients with altered mentation (n = 258, p = 0.04, odds ratio [OR] 1.39, confidence interval [CI] 1.04-1.86) or radiologically confirmed stroke (n = 55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age- and severity-matched controls. CONCLUSIONS: The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.

Cerebrospinal Fluid in Posterior Reversible Encephalopathy Syndrome: Implications of Elevated Protein and Pleocytosis.

BACKGROUND AND PURPOSE: Patients with posterior reversible encephalopathy syndrome (PRES) sometimes undergo analysis of cerebrospinal fluid (CSF) to exclude alternative diagnoses. This study's objectives were to describe the CSF characteristics in patients with PRES and to identify clinical and radiologic findings associated with distinct CSF abnormalities. METHODS: We identified a retrospective cohort of patients with PRES. We compared clinical and radiographic characteristics of those who did versus did not undergo lumbar puncture, described the observed range of CSF findings, and analyzed clinical and radiographic features associated with specific CSF abnormalities. RESULTS: A total of 188 patients were included. Patients with (n = 77) and without (n = 111) CSF analysis had similar clinical and radiographic characteristics. Cerebrospinal fluid protein was elevated in 46 (60%) of 77, with median CSF protein 53 mg/dL (upper limit of normal 45 mg/dL). Protein elevation was significantly associated with radiographic severity (P = .0058) but not with seizure, time from symptom onset, radiographic evidence of diffusion restriction, or contrast enhancement. Five (7%) patients had elevated CSF white blood cells, all of whom had infarction and/or hemorrhage on neuroimaging, and 4 of whom had eclampsia. CONCLUSION: The CSF of most patients with PRES shows a mild protein elevation commensurate with radiographic severity. Cerebrospinal fluid pleocytosis may mark a distinct subtype of PRES with predisposition toward infarction and/or hemorrhage. These findings help clinicians interpret CSF findings in these patients and generate new hypotheses about the pathophysiology of this syndrome.

Intracellular and trans-synaptic regulation of glutamatergic synaptogenesis by EphB receptors.

The majority of mature excitatory synapses in the CNS are found on dendritic spines and contain AMPA- and NMDA-type glutamate receptors apposed to presynaptic specializations. EphB receptor tyrosine kinase signaling has been implicated in both NMDA-type glutamate receptor clustering and dendritic spine formation, but it remains unclear whether EphB plays a broader role in presynaptic and postsynaptic development. Here, we find that EphB2 is involved in organizing excitatory synapses through the independent activities of particular EphB2 protein domains. We demonstrate that EphB2 controls AMPA-type glutamate receptor localization through PDZ (postsynaptic density-95/Discs large/zona occludens-1) binding domain interactions and triggers presynaptic differentiation via its ephrin binding domain. Knockdown of EphB2 in dissociated neurons results in decreased functional synaptic inputs, spines, and presynaptic specializations. Mice lacking EphB1-EphB3 have reduced numbers of synapses, and defects are rescued with postnatal reexpression of EphB2 in single neurons in brain slice. These results demonstrate that EphB2 acts to control the organization of specific classes of mature glutamatergic synapses.

Splenule disguised as pancreatic mass: elucidated with SPECT liver-spleen scintigraphy.

Splenules are congenital foci of healthy splenic tissue that are separate from the main body but are structurally identical to the spleen, derived from mesenchymal buds on the left side of the mesogastrium and commonly seen in or near the tail of the pancreas. We report a case of a 58-year-old male who was found to have a pancreatic tail mass on contrast-enhanced abdominal CT, which was similarly disguised as a pancreatic tail mass on both magnetic resonance cholangiopancreatography and abdominal MRI. A liver spleen scintigraph with Tc sulfur colloid later proved the mass to be a splenule.

Psychological and cumulative cardiovascular effects of repeated angry rumination and visuospatial suppression.

Brooding rumination is associated with depressed mood, increased negative affect, prolonged anger and inhibited cardiovascular (CV) recovery. Distraction from rumination on a stressful interpersonal encounter is associated with faster CV recovery and decreased negative affect. Studies have suggested that a concurrent visuospatial (VS) task inhibits the maintenance of imagery associated with the perseveration of intrusive negative memories. 120 healthy participants were recruited for the study. As an analogue of repeated angry rumination, the authors explored the effects of repeated visual recall of a provocative confederate and the subsequent impact of two visuospatial (VS) distraction tasks on negative affect, blood pressure (BP) and heart rate (HR). Repeated recall of the provocation generated repeatedly elevated HR with a cumulative trend that may have CV disease risk implications for chronic ruminators. VS distraction did not aid recovery compared with the Control task.

Cell adhesion molecules: signalling functions at the synapse.

Many cell adhesion molecules are localized at synaptic sites in neuronal axons and dendrites. These molecules bridge pre- and postsynaptic specializations but do far more than simply provide a mechanical link between cells. In this review, we will discuss the roles these proteins have during development and at mature synapses. Synaptic adhesion proteins participate in the formation, maturation, function and plasticity of synaptic connections. Together with conventional synaptic transmission mechanisms, these molecules are an important element in the trans-cellular communication mediated by synapses.

Reduction of vividness and associated craving in personalized food imagery.

This study aimed to extend recent experimental work on the efficacy of visuo-spatial working memory-based techniques for reducing food cravings by adopting a more naturalistic methodology. Fifty undergraduate women formed images of their favorite foods while performing a visuo-spatial task across six successive trials. Vividness and craving intensity were rated for each food image. Concurrent visuo-spatial processing reduced the vividness of, and craving reactivity to, personally relevant food images. Forehead tracking, a novel self-administered task, proved to be as effective in reducing vividness and craving ratings as the established visuo-spatial working memory laboratory tasks of eye movements, dynamic visual noise, and spatial tapping, and thus presents a simple, accessible technique potentially applicable in the home environment. All four tasks maintained their reducing effect over multiple trials. Individual differences in imaging ability and habitual food craving did not impact upon their effectiveness, indicating that visuo-spatial tasks can be successfully used to reduce food cravings across a range of people.