Fumonisin B1 (FB1) structurally resembles sphingolipids and interferes with their metabolism leading to sphingolipid dysregulation. We questioned if FB1 could exacerbate liver or kidney toxicities in glutathione peroxidase 1 (Gpx1) and catalase (Cat) knockout mice. While higher serum levels of thiobarbituric acid reactive substances (TBARS) and sphinganine (Sa) were measured in Gpx1/Cat knockout mice (Gpx1/Cat KO) than wild type mice after 5 days of FB1 treatment, serum levels of alanine aminotransferase (ALT), sphingosine-1 phosphate (So-1-P), and sphinganine-1 phosphate (Sa-1-P) were found to be relatively low. Although Sa was highly elevated in Gpx1/Cat KO mice and wild mice, lower levels of So and Sa were found in both the kidney and liver tissues of Gpx/Cat KO mice than wild type mice after FB1 treatment. Paradoxically, FB1-induced cellular apoptosis and necrosis were hastened under oxidative stress in Gpx1/Cat KO mice.

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.
Aphasia, Primary Progressive ; Cognition ; Comprehension ; Humans ; Magnetic Resonance Imaging ; Neurofibrillary Tangles ; Neuropsychological Tests ; Parietal Lobe ; Positron-Emission Tomography ; Prefrontal Cortex ; Rabeprazole ; Semantics ; Temporal Lobe

Background/Aims: The controlled attenuation parameter (CAP), based on transient elastography, is widely used for noninvasive assessment of the degree of hepatic steatosis (HS). We investigated the correlation of the degree HS between CAP and ultrasound (US) in patients with HS. Methods: In total, 986 patients with US-based HS who underwent transient elastography within 1 month were evaluated. The US-based grade of HS was categorized as mild (grade 1), moderate (grade 2), or severe (grade 3). Results: The CAP was significantly correlated with the US-based grade of HS (r = 0.458, p < 0.001). The median CAP value of each US-based HS grade showed a positive correlation with grade (271.1, 303.7, and 326.7 dB/m for grades 1, 2, and 3). In a multivariate analysis, the US-based HS grade, body mass index, serum albumin, alanine aminotransferase, and total cholesterol, and liver stiffness were all significantly correlated with the CAP value (all p < 0.05). The areas under the receiver operating characteristic curves for grade 2 to 3 and grade 3 HS were 0.749 (95% confidence interval [CI], 0.714 to 0.784) and 0.738 (95% CI, 0.704 to 0.772). The optimal cut-off CAP values to maximize the sum of the sensitivity and specificity for grade 2 to 3 and grade 3 HS were 284.5 dB/m (sensitivity 78.6%, specificity 61.7%) and 298.5 dB/m (sensitivity 84.6%, specificity 55.6%). Conclusions The correlation of the degree of HS between CAP and US was significantly high in patients with HS, and the optimal cut-off CAP values for grade 2 to 3 and grade 3 HS were 284.5 and 298.5 dB/m.

Background: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. Methods: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. Results: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3–4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5–7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50–59, 60–69, 70–79, and ≥ 80 years of age, respectively. Conclusion In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.