Improvement of Transfusion Practice in Cardiothoracic Surgery Through Implementing a Patient Blood Management Program.

Background: In this study, we examined the impact of a patient blood management (PBM) program on red blood cell (RBC) transfusion practices in cardiothoracic surgery. Methods: The PBM program had 3 components: monitoring transfusions through an order communication system checklist, educating the medical team about PBM, and providing feedback to ordering physicians on the appropriateness of transfusion. The retrospective analysis examined changes in the hemoglobin levels triggering transfusion and the proportions of appropriate RBC transfusions before, during, and after PBM implementation. Further analysis was focused on patients undergoing cardiac surgery, with outcomes including 30-day mortality, durations of intensive care unit and hospital stays, and rates of pneumonia, sepsis, and wound complications. Results: The study included 2,802 patients admitted for cardiothoracic surgery. After the implementation of PBM, a significant decrease was observed in the hemoglobin threshold for RBC transfusion. This threshold dropped from 8.7 g/dL before PBM to 8.3 g/dL during the PBM education phase and 8.0 g/dL during the PBM feedback period. Additionally, the proportion of appropriate RBC transfusions increased markedly, from 23.9% before PBM to 34.9% and 58.2% during the education and feedback phases, respectively. Among the 381 patients who underwent cardiac surgery, a significant reduction was noted in the length of hospitalization over time (p<0.001). However, other clinical outcomes displayed no significant differences. Conclusion: PBM implementation effectively reduced the hemoglobin threshold for RBC transfusion and increased the rate of appropriate transfusion in cardiothoracic surgery. Although transfusion practices improved, clinical outcomes were comparable to those observed before PBM implementation.

Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites.

BACKGROUND: Transmembrane 4 L six family member 5 (TM4SF5) translocates subcellularly and functions metabolically, although it is unclear how intracellular TM4SF5 translocation is linked to metabolic contexts. It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms. METHODS: Here, we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites (MLCSs), using in vitro cells and in vivo animal systems, via approaches by immunofluorescence, proximity labelling based proteomics analysis, organelle reconstitution etc. RESULTS: Upon extracellular glucose repletion following depletion, TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8 (FKBP8) and lysosomal TM4SF5. Proximity labeling showed molecular clustering of phospho-dynamic-related protein I (DRP1) and certain mitophagy receptors at TM4SF5-enriched MLCSs, leading to mitochondrial fission and autophagy. TM4SF5 bound NPC intracellular cholesterol transporter 1 (NPC1) and free cholesterol, and mediated export of lysosomal cholesterol to mitochondria, leading to impaired oxidative phosphorylation but intact tricarboxylic acid (TCA) cycle and ß-oxidation. In mouse models, hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria, both with positive relations to liver malignancy. CONCLUSIONS: Our findings suggested that TM4SF5-enriched MLCSs regulate glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming, presumably while hepatocellular carcinogenesis, recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial reprogramming to support biomolecule synthesis in addition to glycolytic energetics.

Development of simultaneous quantitative analytical method for three active components of Korean mint (Agastache rugosa (Fisch. & C.A.Mey.) Kuntze) extract in human plasma using ultra-high-performance liquid chromatography-tandem mass spectrometry.

Agastache rugosa contains phenolic compounds and flavonoids, and has been extensively used as a traditional herbal medicine. The major components in Agastache rugosa extract (ARE) are rosmarinic acid, tilianin, and acacetin, for which several analytical techniques have been reported. However, these substances have yet to be simultaneously quantified in human plasma. In this study, we aimed to simultaneously determine the three active components of ARE in human plasma by developing a reliable quantitative analytical method using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation of the plasma samples was achieved using an ACQUITY UPLC® BEH C18 column with a gradient mobile phase of water and acetonitrile containing 0.1 % formic acid. Mass spectrometric detection was performed using a triple quadrupole tandem mass spectrometer in negative electrospray ionization (ESI-) and multiple reaction monitoring (MRM) modes. The developed quantitative method was validated for the three active components. All three analytes exhibited a linear response over the ranges of 0.5-50 ng/mL for rosmarinic acid, 0.1-20 ng/mL for acacetin, and 0.5-20 ng/mL for tilianin with a weighting factor of 1/x (where x is the concentration). At three quality control (QC) concentration levels (low, medium, and high), including the lower limit of quantitation (LLOQ), acceptable accuracy (±15 %) was achieved in the intra- and interday validations. The concentration of rosmarinic acid was highest in plasma. Tilianin and acacetin appeared and were eliminated earlier in the plasma than rosmarinic acid. This study provides a successfully validated method that can be used in further clinical applications of Agastache rugosa extracts.

TM4SF5-mediated abnormal food-intake behavior and apelin expression facilitate non-alcoholic fatty liver disease features.

Transmembrane 4 L six family member 5 (TM4SF5) engages in non-alcoholic steatohepatitis (NASH), although its mechanistic roles are unclear. Genetically engineered Tm4sf5 mice fed ad libitum normal chow or high-fat diet for either an entire day or a daytime-feeding (DF) pattern were analyzed for metabolic parameters. Compared to wild-type and Tm4sf5-/- knockout mice, hepatocyte-specific TM4SF5-overexpressing Alb-TGTm4sf5-Flag (TG) mice showed abnormal food-intake behavior during the mouse-inactive daytime, increased apelin expression, increased food intake, and higher levels of NASH features. DF or exogenous apelin injection of TG mice caused severe hepatic pathology. TM4SF5-mediated abnormal food intake was correlated with peroxisomal ß-oxidation, mTOR activation, and autophagy inhibition, with triggering NASH phenotypes. Non-alcoholic fatty liver disease (NAFLD) patients' samples revealed a correlation between serum apelin and NAFLD activity score. Altogether, these observations suggest that hepatic TM4SF5 may cause abnormal food-intake behaviors to trigger steatohepatitic features via the regulation of peroxisomal ß-oxidation, mTOR, and autophagy.

Permanent Anticoagulation Blood-Vessel by Mezzo-Sized Double Re-Entrant Structure.

Having a permanent omniphobicity on the inner surface of the tube can bring enormous advantages, such as reducing resistance and avoiding precipitation during mass transfer. For example, such a tube can prevent blood clotting when delivering blood composed of complex hydrophilic and lipophilic compounds. However, it is very challenging to fabricate micro and nanostructures inside a tube. To overcome these, a wearability and deformation-free structural omniphobic surface is fabricated. The omniphobic surface can repel liquids by its "air-spring" under the structure, regardless of surface tension. Furthermore, it is not lost an omniphobicity under physical deformation like curved or twisted. By using these properties, omniphobic structures on the inner wall of the tube by the "roll-up" method are fabricated. Fabricated omniphobic tubes still repels liquids, even complex liquids like blood. According to the ex vivo blood tests for medical usage, the tube can reduce thrombus formation by 99%, like the heparin-coated tube. So, the surface will soon replace typical coating-based medical surfaces or anticoagulation blood vessels.

Social engagement and subjective health among older adults in South Korea: Evidence from the Korean Longitudinal Study of Aging (2006-2018).

Background: Social engagement serves as the foundation for social connections by providing a sense of belonging, social identity, and fulfillment. Previous studies have mainly focused on the one-way relationship between social engagement and subjective health among older individuals, and little attention has been paid to their mutual relationship. Therefore, this study aimed to examine the mutual association relationship between social engagement and their subjective health in older Koreans. Methods: Seven waves of data samples (aged ≥60 years) from 2006 to 2018 from the Korean Longitudinal Study of Aging (KLoSA) was used in this study. Descriptive analysis, chi-squared tests, 2-year lagged Generalized estimating equation (GEE) model, and cross-lagged panel model were performed to investigate the mutual association between social engagement and subjective health among six survey periods. Results: Results of the GEE model revealed when controlling for other variables, older Koreans who reported good subjective health only had a higher OR (1.678 vs. 1.650, p < 0.001) of participating in social engagement than those who had bad subjective health in 2006-2008 period; the occurrence rate of more social engagement was significantly higher among older adults with good subjective health than among those with bad subjective health (five out six survey periods). Cross-lagged analysis showed similar results that coefficients of social engagement on subjective were relatively larger in three survey periods; coefficients of subjective health on social engagement were relatively larger in the other three survey periods. The impact of social engagement on subjective health might be greater than that of subjective health on social engagement. Conclusion: All-around participation and engagement of older people in society have become a consensus among the international community. In view of the single social engagement activities and less relevant participation channels in Korea, government departments should consider not only regional but also local characteristics to create more social participation opportunities for older individuals.

Eight-week supplementation of Aronia berry extract promoted the glutathione defence system against acute aerobic exercise-induced oxidative load immediately and 30 min post-exercise in healthy adults: a double-blind, randomised controlled trial.

BACKGROUND: Food antioxidants have received prompt attention for controlling oxidative stress encountered in daily life. This study aimed to examine the protective effects of Aronia berry extract (ABE) supplementation on acute aerobic exercise (AAE)-induced oxidative stress in healthy subjects. METHODS: We assessed a battery of antioxidant defence and oxidative stress parameters at pre-exercise, immediately post-exercise and 30 min post-exercise in healthy middle-aged adults with habitually low intakes of fruit and vegetables in an 8-week, double-blind, randomised, controlled clinical trial with two arms (n = 70). The AAE challenge model, characterised as a treadmill exercise for 30 min at 60% VO2 maximum, was applied to load oxidative stress at the end of the study. Pearson's correlation analysis assessed the association between the changes in antioxidant defence capacities and oxidative stress levels. RESULTS: The time-course-dependent oxidative stress was well observed in the placebo group regarding the glutathione peroxidase (GPx) activity and the reduced glutathione (GSH) availability for antioxidant defence and erythrocyte malondialdehyde, interleukin-6 and lactate levels for oxidative damage. Meanwhile, the ABE supplementation effectively strengthened the glutathione defence system by increasing GSH availability and GPx activity immediately post-exercise and 30 min post-exercise. In addition, the scatter plot and linear regression analysis revealed strong negative correlations of GSH availability with oxidised low-density lipoprotein and plasma malonaldehyde levels. CONCLUSION: These findings suggest that daily supplementation of 300 mg ABE might help boost GSH levels and an adaptive antioxidant enzyme defence system of erythrocytes in healthy adults with habitually low fruit and vegetable intakes.

Perioperative Red Blood Cell Transfusion Is Associated With Adverse Cardiovascular Outcomes in Heart Valve Surgery.

BACKGROUND: We examined the relationship between blood transfusion and long-term adverse events to evaluate the clinical impact of red blood cell (RBC) transfusion on patients undergoing cardiac valve surgery. METHODS: From the National Health Insurance Service database, individuals undergoing heart valve surgery were verified, including aortic valve (AV), mitral valve (MV), tricuspid valve (TV), and complex valves (more than 2 valve surgeries). The interested outcomes were incidence of death, ischemic stroke, hemorrhagic stroke, and admission for myocardial infarction during follow-up. Associations between perioperative RBC transfusion and long-term cardiovascular events were analyzed with Cox-proportional hazard model. RESULTS: Perioperative RBC transfusion (±2 days from the day of surgery) was categorized into 0, 1, 2, and >3 units based on the number of packs transfused. From 2003 to 2019, the data of 58,299 individuals were retrieved (51.6% were male and 58% were aged above 60 years). The median follow-up duration was 5.53 years. Of the total cohort, 86.5% received at least 1 transfusion. In multivariable analysis, adverse cardiovascular event risk proportionally increased with transfusion in a dose-dependent manner. The adjusted hazard ratios and 95% confidence intervals of outcomes after the transfusion of 1, 2, and ≥3 units compared to those with no transfusion were as follows: death, 1.53 (1.41-1.66), 1.97 (1.81-2.14), and 3.03 (2.79-3.29); ischemic stroke, 1.27 (1.16-1.39), 1.31 (1.19-1.44), and 1.51 (1.38-1.66); hemorrhagic stroke, 1.38 (1.16-1.66), 1.71 (1.43-2.05), and 2.31 (1.94-2.76); and myocardial infarction 1.35 (1.13-1.62), 1.60 (1.33-1.91), and 1.99 (1.66-2.38), respectively (all P < .01). CONCLUSIONS: In the analysis of the national cohort, perioperative RBC transfusion during heart valve surgery was associated with adverse cardiovascular outcomes correlated with the volume of RBC transfusion.

Influencing factor of COVID-19 vaccination trust and hesitancy in Wonju city, South Korea.

Social capital (SC) has been documented to effectively reduce the spread of diseases, including COVID-19; however, research pertaining to SC and COVID-19 vaccination in Korea is lacking. This cross-sectional study conducted in the city of Wonju, Gangwon Province, Korea (n = 1,096) examined the differences in COVID-19 vaccine trust and hesitancy considering individual characteristics and investigated the effects of SC on COVID-19 vaccine trust and hesitancy. SC was measured based on 14 items pertaining to social trust, network, and norms. Responses regarding COVID-19 screening history, vaccine trust, and vaccine hesitancy were also assessed. SC scores did not differ between sexes, but differed significantly according to age and household income; thus, adults aged 70-79 years had the highest SC scores, and mean SC score increased significantly with income. COVID-19 vaccine trust differed significantly according to age, average household income, social organization involvement, and SC score. COVID-19 vaccine hesitancy differed significantly with age, SC score, and COVID-19 screening history. In univariate logistic regression, age, average household income, social organization involvement, and SC score were significant predictors of vaccine trust; in multivariable analysis, however, the identified predictors were age and SC. In particular, people with an SC score ≥50 were 2.660 times more likely to trust COVID-19 vaccines than those with lower scores. In multivariable analysis, age and SC were significant predictors of vaccine hesitancy. In particular, people with an SC score ≥50 were 1.400 times more likely not to be hesitant about receiving COVID-19 vaccines than people with lower scores. These results indicate that prioritizing policies to increase SC and trust in the government could boost the COVID-19 vaccination rate.

Deep learning model to predict Epstein-Barr virus associated gastric cancer in histology.

The detection of Epstein-Barr virus (EBV) in gastric cancer patients is crucial for clinical decision making, as it is related with specific treatment responses and prognoses. Despite its importance, the limited medical resources preclude universal EBV testing. Herein, we propose a deep learning-based EBV prediction method from H&E-stained whole-slide images (WSI). Our model was developed using 319 H&E stained WSI (26 EBV positive; TCGA dataset) from the Cancer Genome Atlas, and 108 WSI (8 EBV positive; ISH dataset) from an independent institution. Our deep learning model, EBVNet consists of two sequential components: a tumor classifier and an EBV classifier. We visualized the learned representation by the classifiers using UMAP. We externally validated the model using 60 additional WSI (7 being EBV positive; HGH dataset). We compared the model's performance with those of four pathologists. EBVNet achieved an AUPRC of 0.65, whereas the four pathologists yielded a mean AUPRC of 0.41. Moreover, EBVNet achieved an negative predictive value, sensitivity, specificity, precision, and F1-score of 0.98, 0.86, 0.92, 0.60, and 0.71, respectively. Our proposed model is expected to contribute to prescreen patients for confirmatory testing, potentially to save test-related cost and labor.

Liver-originated small extracellular vesicles with TM4SF5 target brown adipose tissue for homeostatic glucose clearance.

Transmembrane 4 L six family member 5 (TM4SF5) is involved in chronic liver disease, although its role in glucose homeostasis remains unknown. TM4SF5 deficiency caused age-dependent glucose (in)tolerance with no link to insulin sensitivity. Further, hepatic TM4SF5 binding to GLUT1 promoted glucose uptake and glycolysis. Excessive glucose repletion caused hepatocytes to secrete small extracellular vesicles (sEVs) loaded with TM4SF5 (hep-sEVTm4sf5 ), suggesting a role for sEVTm4sf5 in glucose metabolism and homeostasis. Hep-sEVTm4sf5 were smaller than sEVControl and recruit proteins for efficient organ tropism. Liver-derived sEVs, via a liver-closed vein circuit (LCVC) using hepatic TM4SF5-overexpressing (Alb-Tm4sf5 TG) mice (liv-sEVTm4sf5 ), improved glucose tolerance in Tm4sf5-/- KO mice and targeted brown adipose tissues (BATs), possibly allowing the clearance of blood glucose as heat independent of UCP1. Taken together, hep-sEVTm4sf5 might clear high extracellular glucose levels more efficiently by targeting BAT compared with hep-sEVControl , suggesting an insulin-like role for sEV™4SF5 in affecting age-related metabolic status and thus body weight (BW).

Systemic TM4SF5 overexpression in ApcMin/+ mice promotes hepatic portal hypertension associated with fibrosis.

Mutation of the gene for adenomatous polyposis coli (APC), as seen in ApcMin/+ mice, leads to intestinal adenomas and carcinomas via stabilization of ß-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or ß-catenin has not been investigated for pathological outcomes. After interbreeding ApcMin/+ with TM4SF5-overexpressing transgenic (TgTM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (ApcMin/+:TgTM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in ApcMin/+ mice. Additional TM4SF5 overexpression increased the stabilization of ß-catenin via reduced glycogen synthase kinase 3ß (GSK3ß) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in ApcMin/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3ß phosphorylation (opposite to that seen in the colon), ß-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old TgTM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver. [BMB Reports 2022; 55(12): 609-614].

TM4SF5-Mediated Regulation of Hepatocyte Transporters during Metabolic Liver Diseases.

Nonalcoholic fatty liver disease (NAFLD) is found in up to 30% of the world's population and can lead to hepatocellular carcinoma (HCC), which has a poor 5-year relative survival rate of less than 40%. Clinical therapeutic strategies are not very successful. The co-occurrence of metabolic disorders and inflammatory environments during the development of steatohepatitis thus needs to be more specifically diagnosed and treated to prevent fatal HCC development. To improve diagnostic and therapeutic strategies, the identification of molecules and/or pathways responsible for the initiation and progression of chronic liver disease has been explored in many studies, but further study is still required. Transmembrane 4 L six family member 5 (TM4SF5) has been observed to play roles in the regulation of metabolic functions and activities in hepatocytes using in vitro cell and in vivo animal models without or with TM4SF5 expression in addition to clinical liver tissue samples. TM4SF5 is present on the membranes of different organelles or vesicles and cooperates with transporters for fatty acids, amino acids, and monocarbohydrates, thus regulating nutrient uptake into hepatocytes and metabolism and leading to phenotypes of chronic liver diseases. In addition, TM4SF5 can remodel the immune environment by interacting with immune cells during TM4SF5-mediated chronic liver diseases. Because TM4SF5 may act as an NAFLD biomarker, this review summarizes crosstalk between TM4SF5 and nutrient transporters in hepatocytes, which is related to chronic liver diseases.

Development and validation of a management system and dataset quality assessment tool for the Radiology Common Data Model (R_CDM): A case study in liver disease.

BACKGROUND: The Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM), a distributed research network, has low clinical data coverage. Radiological data are valuable, but imaging metadata are often incomplete, and a standardized recording format in the OMOP-CDM is lacking. We developed a web-based management system and data quality assessment (RQA) tool for a radiology_CDM (R_CDM) and evaluated the feasibility of clinically applying this dataset. METHODS: We designed an R_CDM with Radiology_Occurrence and Radiology_Image tables. This was seamlessly linked to the OMOP-CDM clinical data. We adopted the standardized terminology using the RadLex playbook and mapped 5,753 radiology protocol terms to the OMOP vocabulary. An extract, transform, and load (ETL) process was developed to extract detailed information that was difficult to extract from metadata and to compensate for missing values. Image-based quantification was performed to measure liver surface nodularity (LSN), using customized Wonkwang abdomen and liver total solution (WALTS) software. RESULTS: On a PACS, 368,333,676 DICOM files (1,001,797 cases) were converted to R_CDM chronic liver disease (CLD) data (316,596 MR images, 228 cases; 926,753 CT images, 782 cases) and uploaded to a web-based management system. Acquisition date and resolution were extracted accurately, but other information, such as "contrast administration status" and "photography direction", could not be extracted from the metadata. Using WALTS, 9,609 pre-contrast axial-plane abdominal MR images (197 CLD cases) were assigned LSN scores by METAVIR fibrosis grades, which differed significantly by ANOVA (p < 0.001). The mean RQA score (83.5) indicated good quality. CONCLUSION: This study developed a web-based system for management of the R_CDM dataset, RQA tool, and constructed a CLD R_CDM dataset, with good quality for clinical application. Our management system and R_CDM CLD dataset would be useful for multicentric and image-based quantification researches.

Compressed Deep Learning to Classify Arrhythmia in an Embedded Wearable Device.

The importance of an embedded wearable device with automatic detection and alarming cannot be overstated, given that 15-30% of patients with atrial fibrillation are reported to be asymptomatic. These asymptomatic patients do not seek medical care, hence traditional diagnostic tools including Holter are not effective for the further prevention of associated stroke or heart failure. This is likely to be more so in the era of COVID-19, in which patients become more reluctant on hospitalization and checkups. However, little literature is available on this important topic. For this reason, this study developed efficient deep learning with model compression, which is designed to use ECG data and classify arrhythmia in an embedded wearable device. ECG-signal data came from Korea University Anam Hospital in Seoul, Korea, with 28,308 unique patients (15,412 normal and 12,896 arrhythmia). Resnets and Mobilenets with model compression (TensorFlow Lite) were applied and compared for the diagnosis of arrhythmia in an embedded wearable device. The weight size of the compressed model registered a remarkable decrease from 743 MB to 76 KB (1/10000), whereas its performance was almost the same as its original counterpart. Resnet and Mobilenet were similar in terms of accuracy, i.e., Resnet-50 Hz (97.3) vs. Mo-bilenet-50 Hz (97.2), Resnet-100 Hz (98.2) vs. Mobilenet-100 Hz (97.9). Here, 50 Hz/100 Hz denotes the down-sampling rate. However, Resnets took more flash memory and longer inference time than did Mobilenets. In conclusion, Mobilenet would be a more efficient model than Resnet to classify arrhythmia in an embedded wearable device.

Crosstalk between TM4SF5 and GLUT8 regulates fructose metabolism in hepatic steatosis.

OBJECTIVE: Transmembrane 4 L six family member 5 (TM4SF5) is likely involved in non-alcoholic steatohepatitis, although its roles and cross-talks with glucose/fructose transporters in phenotypes derived from high-carbohydrate diets remain unexplored. Here, we investigated the modulation of hepatic fructose metabolism by TM4SF5. METHODS: Wild-type or Tm4sf5-/- knockout mice were evaluated via different diets, including normal chow, high-sucrose diet, or high-fat diet without or with fructose in drinking water (30% w/v). Using liver tissues and blood samples from the mice or hepatocytes, the roles of TM4SF5 in fructose-mediated de novo lipogenesis (DNL) and steatosis via a crosstalk with glucose transporter 8 (GLUT8) were assessed. RESULTS: Tm4sf5 suppression or knockout in both in vitro and in vivo models reduced fructose uptake, DNL, and steatosis. Extracellular fructose treatment of hepatocytes resulted in an inverse relationship between fructose-uptake activity and TM4SF5-mediated translocalization of GLUT8 through dynamic binding at the cell surface. Following fructose treatment, TM4SF5 binding to GLUT8 transiently decreased with translocation to the plasma membrane (PM), where GLUT8 separated and became active for fructose uptake and DNL. CONCLUSIONS: Overall, hepatic TM4SF5 modulated GLUT8 localization and activity through transient binding, leading to steatosis-related fructose uptake and lipogenesis. Thus, TM4SF5 and/or GLUT8 may be promising treatment targets against liver steatosis resulting from excessive fructose consumption.

TM4SF5-dependent crosstalk between hepatocytes and macrophages to reprogram the inflammatory environment.

Chronic injury to hepatocytes results in inflammation, steatohepatitis, fibrosis, and nonalcoholic fatty liver disease (NAFLD). The tetraspanin TM4SF5 is implicated in fibrosis and cancer. We investigate the role of TM4SF5 in communication between hepatocytes and macrophages (MΦs) and its possible influence on the inflammatory microenvironment that may lead to NAFLD. TM4SF5 induction in differentiated MΦs promotes glucose uptake, glycolysis, and glucose sensitivity, leading to M1-type MΦ activation. Activated M1-type MΦs secrete pro-inflammatory interleukin-6 (IL-6), which induces the secretion of CCL20 and CXCL10 from TM4SF5-positive hepatocytes. Although TM4SF5-dependent secretion of these chemokines enhances glycolysis in M0 MΦs, further chronic exposure reprograms MΦs for an increase in the proportion of M2-type MΦs in the population, which may support diet- and chemical-induced NAFLD progression. We suggest that TM4SF5 expression in MΦs and hepatocytes is critically involved in modulating the inflammatory environment during NAFLD progression.

Depression in public officials during the COVID-19 pandemic in Paraguay: a web-based study.

BACKGROUND: According to the World Health Organization, the coronavirus disease 2019 (COVID-19) pandemic has created situations that have a negative effect on people and threaten their mental health. Paraguay announced the Estado de Emergencia Sanitaria (Presidential Decree No. 3456) on March 16, 2020, which was followed by the imposition of a 24-h restriction on movement order on March 21. Self-quarantine at home may have been the most effective method of preventing the spread of infectious diseases; however, with the global pandemic becoming more prolonged and the consequent lengthening of the 24-h self-quarantine period, it is highly probable that both physical and psychological problems will arise. METHODS: In this study, a web-based cross-sectional method was used to analyze the factors influencing COVID-19-induced depressive feelings in Paraguayan public officials. RESULTS: Public officials reported a high level of depressive symptoms with a high level of apprehension in early stage of COVID-19. In addition, this study identified that when the self-quarantine period increased, levels of depressive feelings also increased. Since self-quarantine is characterized by the requirement that individuals endure an undetermined period within a confined area, it may have caused stress and anxiety, as well as the consequent experience of depressive feelings. CONCLUSIONS: Paraguayan government should develop a program for the delivery of mental health care and services to public officials in COVID-19 Pandemic period. Moreover, a program is required for people facing deteriorating mental health due to social isolation and loneliness caused by social distancing during the prolonged period of self-quarantine. Finally, mental health care programs should be organized in a community-focused way by utilizing online systems to enhance the effectiveness of mental health recovery.