Cerebral Microbleeds in Critically Ill Patients with Respiratory Failure or Sepsis: A Scoping Review.

Background: Cerebral microbleeds (CMBs) have been described in critically ill patients with respiratory failure, acute respiratory distress syndrome (ARDS), or sepsis. This scoping review aimed to systematically summarize existing literature on critical illness-associated CMBs.

Methods: Studies reporting on adults admitted to the intensive care unit for respiratory failure, ARDS, or sepsis with evidence of CMBs on magnetic resonance imaging were included for review following a systematic search across five databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science) and a two-stage screening process.

Gaining consensus on expert rule statements for acute respiratory failure digital twin patient model in intensive care unit using a Delphi method.

Digital twin technology is a virtual depiction of a physical product and has been utilized in many fields. Digital twin patient model in healthcare is a virtual patient that provides opportunities to test the outcomes of various interventions virtually without subjecting an actual patient to possible harm. This can serve as a decision aid in the complex environment of the intensive care unit (ICU).

Developing DELPHI expert consensus rules for a digital twin model of acute stroke care in the neuro critical care unit.

Introduction: Digital twins, a form of artificial intelligence, are virtual representations of the physical world. In the past 20 years, digital twins have been utilized to track wind turbines' operations, monitor spacecraft's status, and even create a model of the Earth for climate research. While digital twins hold much promise for the neurocritical care unit, the question remains on how to best establish the rules that govern these models.

Polyunsaturated Fatty Acids Mend Macrophage Transcriptome, Glycome, and Phenotype in the Patients with Neurodegenerative Diseases, Including Alzheimer's Disease.

Background: Macrophages of healthy subjects have a pro-resolution phenotype, upload amyloid-β (Aβ) into endosomes, and degrade Aβ, whereas macrophages of patients with Alzheimer's disease (AD) generally have a pro-inflammatory phenotype and lack energy for brain clearance of Aβ.

Objective: To clarify the pathogenesis of sporadic AD and therapeutic effects of polyunsaturated fatty acids (PUFA) with vitamins B and D and antioxidants on monocyte/macrophage (MM) migration in the AD brain, MM transcripts in energy and Aβ degradation, MM glycome, and macrophage clearance of Aβ.

Methods: We followed for 31.

Predictive modeling in neurocritical care using causal artificial intelligence.

Artificial intelligence (AI) and digital twin models of various systems have long been used in industry to test products quickly and efficiently. Use of digital twins in clinical medicine caught attention with the development of Archimedes, an AI model of diabetes, in 2003. More recently, AI models have been applied to the fields of cardiology, endocrinology, and undergraduate medical education.

Progressive apraxia of speech: delays to diagnosis and rates of alternative diagnoses.

Background: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder of speech programming distinct from aphasia and dysarthria, most commonly associated with a 4-repeat tauopathy. Our objective was to better understand the reasons for possible delays or diagnostic errors for patients with PAOS.

Methods: Seventy-seven consecutive PAOS research participants from the Neurodegenerative Research Group were included in this study.

Impact of COVID-19 Governmental Restrictions on Emergency General Surgery Operative Volume and Severity.

Background: To describe the effect of the COVID-19 pandemic on emergency general surgery operative volumes during governmental shutdowns secondary to the pandemic and characterize differences in disease severity, morbidity, and mortality during this time compared to previous years.

Methods: This retrospective cohort study compares patients who underwent emergency general surgery operations at a tertiary hospital from March 1st to May 31st of 2020 to 2019. Average emergent cases per day were analyzed, comparing identical date ranges between 2020 (pandemic group) and 2019 (control group).

Characterization of Anchorless Human PrP With Q227X Stop Mutation Linked to Gerstmann-Sträussler-Scheinker Syndrome In Vivo and In Vitro.

Alteration in cellular prion protein (PrP) localization on the cell surface through mediation of the glycosylphosphatidylinositol (GPI) anchor has been reported to dramatically affect the formation and infectivity of its pathological isoform (PrP). A patient with Gerstmann-Sträussler-Scheinker (GSS) syndrome was previously found to have a nonsense heterozygous PrP-Q227X mutation resulting in an anchorless PrP. However, the allelic origin of this anchorless PrP and cellular trafficking of PrP remain to be determined.

Omega-3 fatty acids increase OXPHOS energy for immune therapy of Alzheimer disease patients.

Sporadic late-onset Alzheimer disease (LOAD) preceded by mild cognitive impairment (MCI) is the most common type of dementia. Long-term studies of immunity to pathogenic amyloid-β (Aβ) in LOAD are lacking. Innate immunity of LOAD patients is malfunctioning in phagocytosis and degradation of Aβ and LOAD patients' macrophage transcriptome and metabolome are deregulated.

Omega-3 Fatty Acids Increase Amyloid-β Immunity, Energy, and Circadian Rhythm for Cognitive Protection of Alzheimer's Disease Patients Beyond Cholinesterase Inhibitors.

Background: The cholinesterase inhibitor therapeutics (CI) approved for use in Alzheimer's disease (AD) are palliative for a limited time.

Objective: To examine the outcome of AD patients with add-on therapy of the omega-3 fatty acid drink Smartfish.

Methods: We performed a prospective study using Mini-Mental State Examination, amyloid-β (Aβ) phagocytosis blood assay, and RNA-seq of peripheral blood mononuclear cells in 28 neurodegenerative patients who had failed their therapies, including 8 subjective cognitive impairment (SCI), 8 mild cognitive impairment (MCI), 2 AD dementia, 1 frontotemporal dementia (FTD), 2 vascular cognitive impairment, and 3 dementia with Lewy bodies (DLB) patients.

Case Report: Drug-induced Leukocytoclastic Vasculitis in a Patient with Classic Ehlers-Danlos Syndrome.

Drug-induced skin reactions are common, but only a small portion (10%) are attributed to a vasculitic mechanism. Small-vessel vasculitis (SVV) with leukocytoclastic histopathology is usually described in drug-induced vasculitis; however, given the shared histopathologic features between drug-induced vasculitis and other SVV, it is crucial to rule out infectious or other autoimmune etiologies underlying the clinical presentation. We hereby sought to present a case of sulfonamide-induced leukocytoclastic vasculitis, limited to the skin, in a patient with Ehlers-Danlos syndrome in order to emphasize the need for a broad diagnostic and clinical exclusion workup.

Publisher Correction: Early preclinical detection of prions in the skin of prion-infected animals.

The original version of this Article contained errors in the author affiliations. Affiliation 2 incorrectly read 'Department of Neurology, The First Hospital of Jilin University, Changchun 130021 Jilin Province, China.'Affiliation 5 incorrectly read 'Department of Otolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061 Shanxi Province, China'Affiliation 9 incorrectly read 'State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Correction to: In Vitro Seeding Activity of Glycoform-Deficient Prions from Variably Protease-Sensitive Prionopathy and Familial CJD Associated with PrP Mutation.

The original version of this article unfortunately contained a mistake. The email address Dr. Wen-Quan Zou, one of the corresponding authors should be written as "wxz6@case.

Early preclinical detection of prions in the skin of prion-infected animals.

A definitive pre-mortem diagnosis of prion disease depends on brain biopsy for prion detection currently and no validated alternative preclinical diagnostic tests have been reported to date. To determine the feasibility of using skin for preclinical diagnosis, here we report ultrasensitive serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays of skin samples from hamsters and humanized transgenic mice (Tg40h) at different time points after intracerebral inoculation with 263K and sCJDMM1 prions, respectively. sPMCA detects skin PrP as early as 2 weeks post inoculation (wpi) in hamsters and 4 wpi in Tg40h mice; RT-QuIC assay reveals earliest skin prion-seeding activity at 3 wpi in hamsters and 20 wpi in Tg40h mice.

In Vitro Seeding Activity of Glycoform-Deficient Prions from Variably Protease-Sensitive Prionopathy and Familial CJD Associated with PrP Mutation.

Both sporadic variably protease-sensitive prionopathy (VPSPr) and familial Creutzfeldt-Jakob disease linked to the prion protein (PrP) V180I mutation (fCJD) have been found to share a unique pathological prion protein (PrP) that lacks the protease-resistant PrP glycosylated at residue 181 because two of four PrP glycoforms are apparently not converted into the PrP from their cellular PrP (PrP). To investigate the seeding activity of these unique PrP molecules, we conducted in vitro prion conversion experiments using serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays with different PrP substrates. We observed that the seeding of PrP from VPSPr or fCJD in the sPMCA reaction containing normal human or humanized transgenic (Tg) mouse brain homogenates generated PrP molecules that unexpectedly exhibited a dominant diglycosylated PrP isoform along with PrP monoglycosylated at residue 181.

Soluble polymorphic bank vole prion proteins induced by co-expression of quiescin sulfhydryl oxidase in E. coli and their aggregation behaviors.

Background: The infectious prion protein (PrP or prion) is derived from its cellular form (PrP) through a conformational transition in animal and human prion diseases. Studies have shown that the interspecies conversion of PrP to PrP is largely swayed by species barriers, which is mainly deciphered by the sequence and conformation of the proteins among species. However, the bank vole PrP (BVPrP) is highly susceptible to PrP from different species.

Characterization of physiochemical properties of caveolin-1 from normal and prion-infected human brains.

Caveolin-1 is a major component protein of the caveolae-a type of flask shaped, 50-100 nm, nonclathrin-coated, microdomain present in the plasma membrane of most mammalian cells. Caveolin-1 functions as a scaffolding protein to organize and concentrate signaling molecules within the caveolae, which may be associated with its unique physicochemical properties including oligomerization, acquisition of detergent insolubility, and association with cholesterol. Here we demonstrate that caveolin-1 is detected in all brain areas examined and recovered in both detergent-soluble and -insoluble fractions.

Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.

Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. Omega-3 fatty acids (ω-3s) and and the ω-3 mediator, resolvin D1, increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.

Tumor Lysis Syndrome: A Unique Solute Disturbance.

Tumor lysis syndrome (TLS) is a life-threatening disorder that is an oncologic emergency. Risk factors for TLS are well-known, but the current literature shows case descriptions of unexpected acute TLS. Solid tumors and untreated hematologic tumors can lyse under various circumstances in children and adults.

Quiescin-sulfhydryl oxidase inhibits prion formation .

Prions are infectious proteins that cause a group of fatal transmissible diseases in animals and humans. The scrapie isoform (PrP) of the cellular prion protein (PrP) is the only known component of the prion. Several lines of evidence have suggested that the formation and molecular features of PrP are associated with an abnormal unfolding/refolding process.

Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on ω-3 supplementation.

Monocyte/macrophages of patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) are defective in phagocytosis and degradation amyloid β (Aβ), but are improved by ω-3 fatty acids (ω-3s). The hypothesis of this study was that active Aβ phagocytosis by macrophages prevents brain amyloidosis and thus maintains cognition. We studied the effects of self-supplementation with a drink with ω-3s, antioxidants, and resveratrol on Mini-Mental State Examination (MMSE) scores, macrophage M1M2 phenotype [the ratio of inflammatory cluster of differentiation (CD)54+CD80 and proresolution markers CD163+CD206], and Aβ phagocytosis in patients initially diagnosed as having MCI or subjective cognitive impairment (SCI).