Ultrasound-based steatosis grading system using 2D-attenuation imaging: an individual patient data meta-analysis with external validation.

BACKGROUND AND RATIONALE: Non-invasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. MAIN RESULTS: A systematic review (EMBASE+MEDLINE, 2018-2022) identified studies, including patients with histologically or MRI-PDFF-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD; n=174, histologically and MRI-PDFF verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis (r=0.60; 95%CI:0.52,0.67; p<0.001), and MRI-PDFF (r=0.70; 95%CI:0.66,0.73; p<0.001) but not with liver stiffness (r=0.03; 95%CI:-0.04,0.11, p=0.343). Steatosis grade was an independent factor associated with ATI (Coefficient: 0.24; 95%CI [0.22, 0.26]; p<0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95%CI [0.58, 0.61]), 0.69 (95%CI [0.67, 0.71]), 0.78 95%CI [0.76, 0.81] and 0.85 95%CI [0.83, 0.88] dB/cm/MHz; all contrasts between grades significant (p<.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cut-offs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ±0.02 and 0.82±0.02 with histologically- and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, non-invasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing MASLD patients.

Comparison of the problem-solving performance of ChatGPT-3.5, ChatGPT-4, Bing Chat, and Bard for the Korean emergency medicine board examination question bank.

Large language models (LLMs) have been deployed in diverse fields, and the potential for their application in medicine has been explored through numerous studies. This study aimed to evaluate and compare the performance of ChatGPT-3.5, ChatGPT-4, Bing Chat, and Bard for the Emergency Medicine Board Examination question bank in the Korean language. Of the 2353 questions in the question bank, 150 questions were randomly selected, and 27 containing figures were excluded. Questions that required abilities such as analysis, creative thinking, evaluation, and synthesis were classified as higher-order questions, and those that required only recall, memory, and factual information in response were classified as lower-order questions. The answers and explanations obtained by inputting the 123 questions into the LLMs were analyzed and compared. ChatGPT-4 (75.6%) and Bing Chat (70.7%) showed higher correct response rates than ChatGPT-3.5 (56.9%) and Bard (51.2%). ChatGPT-4 showed the highest correct response rate for the higher-order questions at 76.5%, and Bard and Bing Chat showed the highest rate for the lower-order questions at 71.4%. The appropriateness of the explanation for the answer was significantly higher for ChatGPT-4 and Bing Chat than for ChatGPT-3.5 and Bard (75.6%, 68.3%, 52.8%, and 50.4%, respectively). ChatGPT-4 and Bing Chat outperformed ChatGPT-3.5 and Bard in answering a random selection of Emergency Medicine Board Examination questions in the Korean language.

Usefulness of MRI Scoring System for Differential Diagnosis between Xanthogranulomatous Cholecystitis and Wall-Thickening Type Gallbladder Cancer.

Purpose: To define an MRI scoring system for differentiating xanthogranulomatous cholecystitis (XGC) from wall-thickening type gallbladder cancer (GBC) and compare the diagnostic performance of the scoring system with the visual assessment of radiologists. Materials and Methods: We retrospectively analyzed 23 and 35 patients who underwent abdominal MRI and were pathologically diagnosed with XGC and wall-thickening-type GBC after surgery, respectively. Three radiologists reviewed all MRI findings. We defined a scoring system using these MRI findings for differentiating XGC from wall-thickening type GBC and compared the area under the curve (AUC) of the scoring system with the visual assessment of radiologists. Results: Nine MRI findings showed significant differences in differentiating the two diseases: diffuse gallbladder wall thickening (p < 0.001), mucosal uniformity (p = 0.002), intramural T2-high signal intensity (p < 0.001), mucosal retraction (p = 0.016), gallbladder stones (p < 0.001), T1-intermediate to high-signal intensity (p = 0.033), diffusion restriction (p = 0.005), enhancement pattern (p < 0.001), and phase of peak enhancement (p = 0.008). The MRI scoring system showed excellent diagnostic performance with an AUC of 0.972, which was significantly higher than the visual assessment of the reviewers. Conclusion: The MRI scoring system showed better diagnostic performance than the visual assessment of radiologists to differentiate XGC from wall-thickening-type GBC.

Multigenerational effects of elevated temperature on host-microbiota interactions in the marine water flea Diaphanosoma celebensis exposed to micro- and nanoplastics.

Rising ocean temperatures are driving unprecedented changes in global marine ecosystems. Meanwhile, there is growing concern about microplastic and nanoplastic (MNP) contamination, which can endanger marine organisms. Increasing ocean warming (OW) and plastic pollution inevitably cause marine organisms to interact with MNPs, but relevant studies remain sparse. Here, we investigated the interplay between ocean warming and MNP in the marine water flea Diaphanosoma celebensis. We found that combined exposure to MNPs and OW induced reproductive failure in the F2 generation. In particular, the combined effects of OW and MNPs on the F2 generation were associated with key genes related to reproduction and stress response. Moreover, populations of predatory bacteria were significantly larger under OW and MNP conditions during F2 generations, suggesting a potential link between altered microbiota and host fitness. These results were supported by a host transcriptome and microbiota interaction analysis. This research sheds light on the complex interplay between environmental stressors, their multigenerational effects on marine organisms, and the function of the microbiome.

The S-S.M.A.R.T: A New Prognostic Tool for Patients with Suspected Sepsis in the Emergency Department.

Background: The sepsis screening tool is essential because it enables the rapid identification of high-risk patients and facilitates prompt treatment. Quick Sequential Organ Failure Assessment (qSOFA) is a widely used screening tool for sepsis. However, it has limitations in predicting patient prognosis. We developed the S-S.M.A.R.T (sepsis evaluation with shock index, mental status, age, and ROX index on triage) and aimed at evaluating it as a screening tool for patients with suspected sepsis in the emergency department. Methods: We conducted a single-center retrospective chart review of patients with suspected sepsis in the emergency department. We compared the prognosis prediction abilities of the S-S.M.A.R.T and qSOFA scores in patients with suspected sepsis. The primary outcome was 7-day mortality, and the secondary outcomes included 30-day mortality and ICU admission. The receiver operating characteristic (ROC) curve analysis and the chi-square test were used. Results: In total, 401 patients were enrolled. The mean age of the patients was 72.2 ± 15.6 years, and 213 (53.1%) of them were female. The S-S.M.A.R.T had superior predictive ability for prognosis of patients with suspected sepsis compared to qSOFA (area under the ROC curve (AUC) of 0.789 vs. 0.699; p=0.02 for 7-day mortality, AUC of 0.786 vs. 0.681; p < 0.001 for 30-day mortality, AUC 0.758 vs 0.717; p=0.05 for ICU admission). Conclusion: The S-S.M.A.R.T can be useful in predicting the prognosis of patients with suspected sepsis in the emergency department.

Synergistic adverse effects of microfibers and freshwater acidification on host-microbiota interactions in the water flea Daphnia magna.

Microfibers are the most common type of microplastics in freshwater environments. Anthropogenic climate stressors, such as freshwater acidification (FA), can interact with plastic pollution to disrupt freshwater ecosystems. However, the underlying mechanisms responsible for the interactive effects of microfibers and FA on aquatic organisms remain poorly understood. In this study, we investigated individual Daphnia magna-microbiota interactions affected by interactions between microfibers and FA (MFA). We found that the accumulated amount of microfibers in pH-treatment groups was significantly higher than in the control groups, resulting in negative consequences on reproduction, growth, and sex ratio. We also observed that MFA interactions induced immunity- and reproduction-related biological processes. In particular, the abundance of pathogenic bacteria increased only in MFA groups, indicating that MFA interactions can cause intestinal damage. Our integrated analysis of microbiomes and host transcriptomes revealed that synergistic adverse effects of MFAs are closely related to changes in microbial communities, suggesting that D. magna fitness and the microbial community are causally linked. These finding may help elucidate the toxicity mechanisms governing the responses of D. magna to microfibers and acidification interactions, and to host-microbiome-environment interactions.

US Attenuation Imaging for the Evaluation and Diagnosis of Fatty Liver Disease.

Purpose: This study aimed to determine whether the attenuation coefficient (AC) from attenuation imaging (ATI) was correlated with visual US assessment in patients with hepatic steatosis. Moreover, it aimed to assess whether the patient's blood chemistry results and CT attenuation were correlated with AC. Materials and Methods: Patients who underwent abdominal US with ATI between April 2018 and December 2018 were included in this study. Patients with chronic liver disease or cirrhosis were excluded. The correlation between AC and other parameters, such as visual US assessment, blood chemistry results, liver attenuation, and liver-to-spleen (L/S) ratio, were analyzed. AC values according to visual US assessment grades were compared using analysis of variance. Results: A total of 161 patients were included in this study. The correlation coefficient between US assessment and AC was 0.814 (p < 0.001). The mean AC values for the normal, mild, moderate, and severe grades were 0.56, 0.66, 0.74, and 0.85, respectively (p < 0.001). Alanine aminotransferase levels were significantly correlated with AC (r = 0.317, p < 0.001). The correlation coefficients between liver attenuation and AC and between L/S ratio and AC were -0.702 and -0.626, respectively (p < 0.001). Conclusion: Visual US assessment and AC showed a strong positive correlation with the discriminative value between the groups. Computed tomography attenuation and AC showed a strong negative correlation.

Are serial neuron-specific enolase levels associated with neurologic outcome of ECPR patients: A retrospective multicenter observational study.

AIM OF THE STUDY: This study aims to evaluate whether neuron-specific enolase (NSE) level at 48 h after extracorporeal cardiopulmonary resuscitation (ECPR) is associated with neurologic outcomes at 6 months after hospital discharge. METHODS: This was a retrospective, multicenter, observational study of adult patients who received ECPR between May 2010 and December 2016. In the two hospitals involved in this study, NSE measurements were a routine part of the protocol for patients who received ECPR. Serial NSE levels were measured in all patients with ECPR. NSE levels were measured 24, 48, and 72 h after ECPR. The primary outcome was Cerebral Performance Categories (CPC) scale at 6 months after hospital discharge according to NSE levels at 48 h after ECPR. RESULTS: At follow-up 6 months after hospital discharge, favorable neurologic outcomes of CPC 1 or 2 were observed in 9 (36.0%) of the 25 patients, and poor neurologic outcomes of CPC 3, 4, or 5 were observed in 16 (64%) patients. NSE levels at 24 h in the favorable and poor neurologic outcome groups were 58.3 (52.5-73.2) µg/L and 64.2 (37.9-89.8) µg/L, respectively (p = 0.95). NSE levels at 48 h in the favorable and poor neurologic outcome groups were 52.1 (22.3-64.9) µg/L and 302.0 (62.8-360.2) µg/L, respectively (p = 0.01). NSE levels at 72 h were 37.2 (12.5-53.2) µg/L and 240.9 (75.3-370.0) µg/L, respectively (p < 0.01). In receiver operating characteristic (ROC) curve analysis, as the predictor of poor outcome, the optimal cut-off value for NSE level at 48 h was 140.5 µg/L, and the area under the curve (AUC) was 0.844 (p < 0.01). The optimal cut-off NSE level at 72 h was 53.2 µg/L, and the AUC was 0.897 (p < 0.01). CONCLUSIONS: NSE level at 72 h displayed the highest association with neurologic outcome after ECPR, and NSE level at 48 h was also associated with neurologic outcome after ECPR.

Nanoplastics induce epigenetic signatures of transgenerational impairments associated with reproduction in copepods under ocean acidification.

Ocean acidification (OA) is one of many major global climate changes that pose a variety of risks to marine ecosystems in different ways. Meanwhile, there is growing concern about how nanoplastics (NPs) affect marine ecosystems. Combined exposure of marine organisms to OA and NPs is inevitable, but their interactive effects remain poorly understood. In this study, we investigated the multi- and transgenerational toxicity of NPs on copepods under OA conditions for ten generations. The findings revealed that OA and NPs have a synergistic negative effect on copepod reproduction across generations. In particular, the transgenerational groups showed reproductive impairments in the F1 and F2 generations (F1T and F2T), even though they were never exposed to NPs. Moreover, our epigenetic examinations demonstrated that the observed intergenerational reproductive impairments are associated with differential methylation patterns of specific genes, suggesting that the interaction of OA and NPs can pose a significant threat to the sustainability of copepod populations through epigenetic modifications. Overall, our findings provide valuable insight into the intergenerational toxicity and underlying molecular mechanisms of responses to NPs under OA conditions.

Gray matter differences associated with menopausal hormone therapy in menopausal women: a DARTEL-based VBM study.

Menopausal hormone therapy (MHT) in women can reduce troublesome menopause symptoms and prevent cognitive decline. This cross-sectional study investigated the MHT-related effect on brain morphology and its association with sex hormones in menopausal women by using an optimized diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL)-based voxel-based morphometry (VBM) method. Twenty-one menopausal women without MHT (noMHT) and 20 menopausal women with MHT were included in this study. Magnetic resonance imaging data were processed using SPM 12 with DARTEL-based VBM whole brain analysis approach. A 2-sample t-test and analysis of covariance (ANCOVA) adjusting for age and total intracranial volume were used to compare GM volume between noMHT and MHT women. The association between MHT (treatment period, hormones levels) and brain volume variations were analyzed by Spearman correlation. MHT women showed significantly larger volumes of the superior/middle/inferior frontal gyri, hypothalamus, inferior temporal gyrus, parahippocampal gyrus, hippocampus, cerebellar cortex, postcentral gyrus, precuneus, angular gyrus, supplementary motor area, superior occipital gyrus, and precentral gyrus compared to the noMHT women. The volumes of the angular gyrus and hypothalamus in MHT women positively correlated with treatment period. On the other hand, the hypothalamic volume negatively correlated with FSH and LH levels, and the volumes of the inferior frontal gyrus, and angular gyrus negatively correlated with progesterone levels, respectively. MHT-treated women showed larger GM volume than noMHT women. The anatomical structures that showed greater volume in association with MHT included the deep brain areas, frontal, temporal, parietal, and occipital gyri.

Research trends on causes of Kawasaki disease in the COVID-19 era: focus on viral infections.

Despite studies on the etiology of Kawasaki disease (KD) ongoing for half a century since its discovery, its cause has not yet been clearly identified. Although the clinical, epidemiological, and pathophysiological characteristics of KD are presumed to be closely related to infectious diseases, studies of various pathogens to identify its etiology have been actively conducted. To date, bacteria, fungi, and viruses have been investigated to determine the relationship between KD and infection, among which viruses have attracted the most attention. In particular, during the coronavirus disease 2019 pandemic, there were many reports in Europe of a sharp increase in cases of Kawasaki-like disease (KLD), while conflicting reports that the prevalence of KD decreased due to thorough "social distancing" or "wearing mask" in Asian countries drew more attention regarding the association between KD and viral infection. Therefore, the differential diagnosis of KD from KLD with these similar spectra has become a very important issue; simultaneously, research to solve questions about the association between KD and viral infections, including sudden acute respiratory syndrome coronavirus 2, is drawing attention again. Moreover, a new concept has emerged that immune responses occurring in patients with KD can be caused by the pathogen itself as well as host cells damaged by infection. This paper summarizes the research trends into KD etiology and related pathophysiology, especially its association with viral infections, and present future research tasks to increase our understanding of KD.

Experience of operating a medical humanities course at one medical school during the COVID-19: a retrospective study.

BACKGROUND: This study summarizes the experience of operating a 'Medical Humanities' course, which was taught remotely to maintain activities and discussions at medical schools in Daegu, Korea during the sudden and unexpected coronavirus disease 2019 (COVID-19). METHODS: The subjects of this study were 73 first- and 79 second-grade medical students who took the medical humanities (1) and (2) courses among first- and second-grade students of Yeungnam University College of Medicine in 2020. Of the 152 students who agreed to the online survey, 123 completed the survey. Self-, environmental, and program evaluations were conducted on the study subjects, and differences according to grade and gender were analyzed. RESULTS: As a result of the study, a significant difference between self-evaluation and environmental evaluation was confirmed. Self-evaluation was determined to be higher in the first grade than in the second grade. The environmental evaluation showed that male students were more satisfied than female students and students generally had difficulties in the classroom environment. Of the applications used in class, the highest satisfaction was observed with KakaoTalk (Kakao Corp.) and Zoom (Zoom Video Communications Inc.). At the end of COVID-19, the students preferred online classes. CONCLUSION: If the learning environment for online classes is well prepared and systematic provisions are made, such as class operations that are suitable for the subject, effective education and learning can be achieved by taking advantage of both face-to-face and online classes.

[CT Findings of Mucinous Adenocarcinoma Arising from the Renal Calyx in Horseshoe Kidney: A Case Report]. / 말굽 ì‹ ìž¥ì˜ ì‹ ë°°ì—ì„œ 발생한 원발성 ì ì•¡ì„± ì„ ì•”ì˜ CT 소견: 증례 ë³´ê³ .

Mucinous adenocarcinoma of the kidney is an extremely rare cystic malignant tumor with a poor prognosis that occurs in the pelvicalyceal system. Pre-opeartive diagnosis is very difficult because the tumor's clinical and imaging features are nonspecific. Here we report a case of primary mucinous adenocarcinoma arising from the horseshoe kidney in a 69-year-old male, focusing on CT findings. The tumor was a complex cystic mass with irregular wall thickening, multifocal calcifications, and septa and progressed to pseudomyxoma peritonei postoperatively.

Short- and long-term single and combined effects of microplastics and chromium on the freshwater water flea Daphnia magna.

In this study, we investigated the individual and combined effects of microplastics (MPs) and chromium (Cr) on the freshwater water flea Daphnia magna by measuring mortality, bioaccumulation, antioxidative response, multixenobiotic resistance activity, and sestrin-related mitochondrial biogenesis in short-term assays and in vivo endpoints including reproduction and adult survival rate in long-term assays. Exposure to MPs, Cr, and their combination caused significant deleterious effects and acute toxicity in D. magna. Alterations in oxidative stress occurred in the groups treated with MPs and Cr alone and together. However, upon co-exposure to MPs, the Cr concentration, measured by inductively coupled plasma optical emission spectroscopy, decreased, suggesting that MPs and Cr interact with each other. Based on enzymatic activities, we noted a decrease in MP egestion via inhibition of P-glycoprotein activity in the MP-exposed groups, and multidrug resistance-associated protein activity increased in some of the MP-exposed animals depending on Cr concentration. On the other hand, MP exposure seemed to lead to mitochondrial transcription dysfunction induced by Cr via sestrin-related mitochondrial biogenesis. Overall, these results indicate that co-exposure to MPs and Cr causes acute toxicity in D. magna but lacks the chronic toxicity (21 days) and mitochondrial dysfunction caused by Cr exposure alone.

Usefulness of 2D shear wave elastography for the evaluation of hepatic fibrosis and treatment response in patients with autoimmune hepatitis.

PURPOSE: The purpose of this study was to determine the usefulness of two-dimensional shear wave elastography (2D SWE) in the assessment of liver stiffness (LS) and dispersion slope (DS) to evaluate hepatic fibrosis and the treatment response in patients with autoimmune hepatitis (AIH). METHODS: Patients diagnosed with AIH who underwent 2D SWE between June 2014 and June 2021 were enrolled in this retrospective study. The patients were classified into four groups according to the histologic stage of fibrosis (F1-F4). The baseline characteristics, laboratory test results, histologic results, and 2D SWE results were analyzed. The diagnostic performance of LS measurements in hepatic fibrosis staging was investigated, and variables were compared before and after steroid treatment for AIH. RESULTS: In total, 69 patients were analyzed. The LS values differed according to the stage of liver fibrosis (P<0.001). The area under the curve for LS was 0.903, 0.815, and 0.854 for ≥F2, ≥F3, and F4, respectively. The diagnostic performance of LS measurements was significantly greater than that of serum biomarkers, except for fibrosis index-4 for F4 (P<0.05). Significant differences were observed in follow-up examinations in both the LS value and DS in patients who received steroid therapy (P=0.012 and P=0.011, respectively). CONCLUSION: In conclusion, 2D SWE is a useful method for the assessment of hepatic fibrosis in patients with AIH. In follow-up examinations, LS and DS can be used as reliable parameters to evaluate the treatment response of AIH.

Environmentally relevant concentrations of microplastics modulated the immune response and swimming activity, and impaired the development of marine medaka Oryzias melastigma larvae.

Microplastics (MPs), due to their impacts on the ecosystem and their integration into the food web either through trophic transfer or ingestion directly from the ambient environment, are an emerging class of environmental contaminants posing a great threat to marine organisms. Most reports on the toxic effects of MPs exclusively focus on bioaccumulation, oxidative stress, pathological damage, and metabolic disturbance in fish. However, the collected information on fish immunity in response to MPs is poorly defined. In particular, little is known regarding mucosal immunity and the role of mucins. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 6.0 µm beads of polystyrene microplastics (PS-MPs) at three environmentally relevant concentrations (102 particles/L, 104 particles/L, and 106 particles/L) for 14 days. The experiment was carried out to explore the developmental and behavioural indices, the transcriptional profiles of mucins, pro-inflammatory, immune, metabolism and antioxidant responses related genes, as well as the accumulation of PS-MPs in larvae. The results revealed that PS-MPs were observed in the gastrointestinal tract, with a concentration- and exposure time-dependent manner. No significant difference in the larval mortality was found between the treatment groups and the control, whereas the body length of larvae demonstrated a significant reduction at 106 particles/L on 14 days post-hatching. The swimming behaviour of the larvae became hyperactive under exposure to 104 and 106 particles/L PS-MPs. In addition, PS-MP exposure significantly up-regulated the mucin gene transcriptional levels of muc7-like and muc13-like, however down-regulated the mucin gene expression levels of heg1, muc2, muc5AC-like and muc13. The immune- and inflammation and metabolism-relevant genes (jak, stat-3, il-6, il-1ß, tnf-а, ccl-11, nf-κb, and sod) were significantly induced by PS-MPs at 104 and 106 particles/L compared to the control. Taken together, this study suggests that PS-MPs induced inflammation response and might obstruct the immune functions and retarded the growth of the marine medaka larvae even at environmentally relevant concentrations.

A study on the mental health of students at a medical school during COVID-19 outbreak: a retrospective study.

BACKGRUOUND: In this study, the degree of anxiety, depression, and stress caused by coronavirus disease 2019 (COVID-19) was identified, as well as the need for psychological prevention measures among medical students in the Daegu region that was designated the first special disaster area due to the spread of COVID-19. METHODS: The subjects of this study were 318 medical students in Daegu who voluntarily participated in an online test using the Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised Korean version. As a result of the test, risk students received immediate telephone counseling, and the effect of this telephone counseling was analyzed. RESULTS: There were no differences in depression, anxiety, or stress according to gender and grade. As a result of immediate telephone counseling for risk students, significant differences were found in depression, anxiety, and stress, and the counseling was found to be effective. CONCLUSION: For medical students who are easily exposed to stress, the importance of psychological prevention measures and effectiveness of non-face-to-face counseling should be recognized. In the field of medical education, we must do our best to build a system that can be used immediately at the appropriate time for these programs.

Oxidative stress-mediated synergistic deleterious effects of nano- and microplastics in the hypoxia-conditioned marine rotifer Brachionus plicatilis.

While pollution due to nano- and micro-sized plastics (NMPs) and hypoxic conditions both occur in coastal areas, the deleterious potential of co-exposure to hypoxia and NMPs (hypoxia and micro-sized plastics, HMPs; hypoxia and nano-sized plastics, HNPs) is largely unclear. Here, we provide evidence for multigenerational effects of HMP and HNP in the marine rotifer Brachionus plicatilis by investigating changes in its life traits, antioxidant system, and hypoxia-inducible factor (HIF) pathway using an orthogonal experimental design, with nanoscale and microscale particles measuring 0.05 µm and 6.0 µm in diameter, respectively, and hypoxic conditions of 0.5 mg/L for six generations. Combined exposure to NMPs and hypoxia caused a significant decrease in fecundity and overproduction of reactive oxygen species (ROS). The HIF pathway and circadian clock genes were also significantly upregulated in response to HMP and HNP exposure. In particular, synergistic deleterious effects of HNP were evident, suggesting that size-dependent toxicity can be a major driver of the effects of hypoxia and NMP co-exposure. After several generations of exposure, ROS levels returned to basal levels and transcriptomic resilience was observed, although rotifer reproduction remained suppressed. These findings help eluciating the underlying molecular mechanisms involved in responses to plastic pollution in hypoxic conditions.

Rationale and methods of the Antioxidant and NMDA receptor blocker Weans Anoxic brain damage of KorEa OHCA patients (AWAKE) trial.

BACKGROUND: Ischemic brain injury is a major hurdle that limits the survival of resuscitated out-of-hospital cardiac arrest (OHCA). METHODS: The aim of this study is to assess the feasibility and potential for reduction of ischemic brain injury in adult OHCA patients treated with high- or low-dose Neu2000K, a selective blocker of N-methyl-D-aspartate (NMDA) type 2B receptor and also a free radical scavenger, or given placebo. This study is a phase II, multicenter, randomized, double-blinded, prospective, intention-to-treat, placebo-controlled, three-armed, safety and efficacy clinical trial. This trial is a sponsor-initiated trial supported by GNT Pharma. Successfully resuscitated OHCA patients aged 19 to 80 years would be included. The primary outcome is blood neuron-specific enolase (NSE) level on the 3rd day. The secondary outcomes are safety, efficacy defined by study drug administration within 4 h in > 90% of participants, daily NSE up to 5th day, blood S100beta, brain MRI apparent diffusion coefficient imaging, cerebral performance category (CPC), and Modified Rankin Scale (mRS) at 5th, 14th, and 90th days. Assuming NSE of 42 ± 80 and 80 ± 80 µg/L in the treatment (high- and low-dose Neu2000K) and control arms with 80% power, a type 1 error rate of 5%, and a 28% of withdrawal prior to the endpoint, the required sample size is 150 patients. DISCUSSION: The AWAKE trial explores a new multi-target neuroprotectant for the treatment of resuscitated OHCA patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03651557 . Registered on August 29, 2018.

Regional Analysis of Liver Surface Nodularity in a Single Axial MR Image for Staging Liver Fibrosis.

BACKGROUND: The assessment of liver surface nodularity (LSN) for staging hepatic fibrosis is restricted in clinical practice because it requires customized software and time-consuming procedures. A simplified method to estimate LSN score may be useful in the clinic. PURPOSE: To evaluate the regional analysis of LSN and processing time in a single axial liver MR image for staging liver fibrosis. STUDY TYPE: Retrospective. POPULATION: A total of 210 subjects, a multicenter study. FIELD STRENGTH/SEQUENCE: A 3 T/noncontrast gradient echo T1WI. ASSESSMENT: Subjects were divided into five fibrosis groups (F0  = 29; F1  = 20; F2  = 32; F3  = 50; F4  = 79) based on the METAVIR fibrosis scoring system. The mean LSN (on three slices) and regional LSN (on one slice) measurements, and the processing times, are compared. The regional LSN scores in five regions-of-interests (ROI1-5 ) were analyzed in a single axial MRI at the level of the hilum by two independent observers. STATISTICAL TESTS: Regional variations in LSN scores were compared using ANOVA with Tukey test. Agreement between the mean and regional LSN measurements was evaluated using Pearson correlation coefficients (r) and Bland-Altman plots. The diagnostic performance of mean and regional LSN scores according to fibrosis stage was evaluated with the AUROC. A P value < 0.05 was considered statistically significant. RESULTS: Total processing time for a regional LSN measurement (3.6 min) was 75.5% less than that for mean LSN measurement (14.7 min). Mean LSN scores and all five regional LSN scores showed significant differences between fibrosis groups. Among regional LSN scores, ROI5 showed the highest AUROC (0.871 at cut-off 1.12) for discriminating F0-2 vs. F3-4 and the best correlation with mean LSN score (r = 0.800, -0.07 limit of agreement). CONCLUSION: Quantitative regional LSN measurement in a single axial MR image reduces processing time. Regional ROI5 LSN score might be useful for clinical decision-making and for distinguishing the difference between early fibrosis (F0-2 ) and advanced fibrosis (F3-4 ) in the liver. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.