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"Solomon, Michael (Michael Ray)"
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Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology
Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.
We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.
Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).
Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.
Journal Article
The Interleukin-1 Balance During Encephalitis Is Associated With Clinical Severity, Blood-Brain Barrier Permeability, Neuroimaging Changes, and Disease Outcome
Background. Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood. Methods. We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging–based temporal lobe volume. Results. Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P = .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P = .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%; P = .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P = .012) and a positive correlation with serum IL-1α level (P = .0003) and CSF IL-1β level (P = .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P = .007) and CSF specimens from all patients (P = .016); the IL-10 level correlated inversely with BBB permeability (P = .005). Conclusions. A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis.
Journal Article
CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes
The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5–6, 2024 (
http://www.cvot.org
).
Journal Article
What Do Industry-Specialist Auditors Know?
An experimental investigation of what industry-specialist auditors know is presented to probe the knowledge implication of industry specialists' focused training and narrow, but deep, direct experiences. Industry specialists are defined as auditors who are so designed by their firms and whose training and practice experience largely are in a particular industry. Two experiments are used to test hypotheses about error and nonerror knowledge quantity and frequency accuracy gains from industry specialization using a 2-by-2 design in which health- and financial-specialist auditors make judgments for both health and financial clients. Results suggest that the focused training and concentrated experiences of industry-specialist auditors have a greater effect on nonerror knowledge than on financial statement error knowledge.
Journal Article
\YO, LIBRO\: JUAN RUIZ AND THE IDEA OF THE BOOK (SPAIN)
Although the enigmatic Libro del arcipreste is the most heavily glossed piece of medieval Spanish literature, few critics agree on the nature of Juan Ruiz's creation. The ambiguity which characterizes the Libro arises from an author who describes himself as an archpriest, and professes his pious motives, yet metaphorically links himself, \"yo, libro,\" with a collection of diverging textual entities that contradict his expressed idea of the book. In medieval Castile the book was not only a container of valuable information, but a divine entity that was functionally related to a holy person and a sacred place. Alfonso X used the book as a symbol of his kingship and as an instrument to reestablish, reorganize, and regulate Christian Spain after the Reconquest. As centripetal constructs in the medieval episteme, a book, a place, and a person stood in their totality for the divine Principle, while they unified the individual marks of a theocentric semiosis, and thus presented coherent norms (roads) for human conduct. Although medieval theologians and cosmologists taught that God had left traces of himself in all of creation, they recognized that after the Fall man's ability to read the Book of Nature was impaired by the multiplicity and fragmentation wrought by sin and error. It was imperative, therefore, that all Christians mediate, through the act of commentary, all discord in order to reestablish and fortify a road of corrective regress. In this thesis commentary refers to any act that orders, unites, and clarifies by way of secondary markings. Such an act may be manifest in activities as diverse as cultivating a field, beautifying a monastic garden, and glossing a holy text. The book in the Middle Ages was not only a collection of graphic commentaries, but a surface upon which diverging textual entities could be reworked into clearer manifestations of the via recta. The Libro de arcipreste is a commentary-provoking instrument. Juan Ruiz effectively manipulates the medieval idea of the book to create a surface--perhaps better visualized as a table--upon which complex textual entities are re-presented as pretexts that must be glossed, ordered, and unified according to the will and disposition of the reader/commentator.
Dissertation
Herpes simplex virus encephalitis in pregnancy - a case report and review of reported patients in the literature
Background
Herpes simplex virus (HSV) encephalitis is the most common sporadic cause of encephalitis with significant morbidity and mortality that is drastically reduced by early antiviral treatment.
Case presentation
We report a 37 year old woman, 33 weeks pregnant, who presented with seizures due to proven HSV-1 encephalitis, and who had had a previous episode of probable viral encephalitis aged 14 years. She was successfully treated with aciclovir on both occasions and, in the latter, went on to deliver a healthy infant. This case is compared with 17 cases of HSV encephalitis in pregnancy in the literature identifying a predominance in the late 2nd and 3rd trimesters, perhaps in part due to immunological changes in pregnancy. The clinical presentation is also compared with non-pregnant patients with HSV encephalitis in the largest prospective UK and European studies. We also present practical advice on management from recent national guidelines.
Conclusion
When pregnant women present with new seizures, headache, impaired consciousness or altered behaviour urgent investigation is required to identify common diagnoses, such as eclampsia, venous sinus thrombosis and metabolic disturbances. Nevertheless, viral encephalitis is a very treatable cause of this presentation with potentially serious complications if missed, and may be more common in latter stages of pregnancy. Encephalitis should not be discounted if the patient is afebrile, has a normal Glasgow coma score, or the cerebrospinal fluid white cell count is only slightly elevated, as these features are well recognised in viral encephalitis.
Journal Article
Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology: e0146288
Background Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. Methods We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Results Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Conclusions Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.
Journal Article
Medieval Iberia
Medieval Iberia was rich in sociolinguistic and cultural diversity. This volume explores the culture, history, literature and language of the Peninsula in an attempt to understand its cultural-political complexity and its legacy. Principal themes include the representation of minority groups in the community; the challenge of social contact that could bring mutual absorption of influence or conflict; the effects of linguistic interaction and development; and the dissemination of cultural and scientific knowledge within and beyond the borders of the Peninsula. Modern interpretations of Medieval Iberia are neither static nor definitive in this kaleidoscopic field of investigation. EDITORS: Ivy A. Corfis and Ray Harris-Northall are Professors of Spanish at the University of Wisconsin-Madison. OTHER CONTRIBUTORS: Pablo Ancos, William J. Courtney, Thomas D. Cravens, Frank Domínguez, Noel Fallows, Charles F. Fraker, E. Michael Gerli, Kristin Neumayer, Stanley G. Payne, Joel Rini, Joseph T. Snow, Michael Solomon.
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