Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

External validation of the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 pneumonia managed on high-flow nasal cannula therapy: a multicenter retrospective observational study in Japan.

BACKGROUND: The HACOR score for predicting treatment failure includes vital signs and acid-base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO2). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan. METHODS: This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022. The HACOR score and ROX index were calculated at 2, 6, 12, 24, and 48 h after stating HFNC therapy. The primary outcome was treatment failure (requirement for intubation or occurrence of death within 7 days). We calculated the area under the receiver operating characteristic curve (AUROC) and assessed the diagnostic performance of these indicators. The 2-h time-point prediction was considered the primary analysis and that of other time-points as the secondary analysis. We also assessed 2-h time-point sensitivity and specificity using previously reported cutoff values (HACOR score > 5, ROX index < 2.85). RESULTS: We analyzed 300 patients from 9 institutions (median age, 60 years; median SpO2/FiO2 ratio at the start of HFNC therapy, 121). Within 7 days of HFNC therapy, treatment failure occurred in 127 (42%) patients. The HACOR score and ROX index at the 2-h time-point exhibited AUROC discrimination values of 0.63 and 0.57 (P = 0.24), respectively. These values varied with temporal changes-0.58 and 0.62 at 6 h, 0.70 and 0.68 at 12 h, 0.68 and 0.69 at 24 h, and 0.75 and 0.75 at 48 h, respectively. The 2-h time-point sensitivity and specificity were 18% and 91% for the HACOR score, respectively, and 3% and 100% for the ROX index, respectively. Visual calibration assessment revealed well calibrated HACOR score, but not ROX index. CONCLUSIONS: In COVID-19 patients receiving HFNC therapy in Japan, the predictive performance of the HACOR score and ROX index at the 2-h time-point may be inadequate. Furthermore, clinicians should be mindful of time-point scores owing to the variation of the models' predictive performance with the time-point. Trial registration UMIN (registration number: UMIN000050024, January 13, 2023).

Modeling of Retina and Optic Nerve Ischemia-Reperfusion Injury through Hypoxia-Reoxygenation in Human Induced Pluripotent Stem Cell-Derived Retinal Ganglion Cells.

Retinal ganglion cells (RGCs) are specialized projection neurons that constitute part of the retina, and the death of RGCs causes various eye diseases, but the mechanism of RGC death is still unclear. Here, we induced cell death in human induced pluripotent stem cell (hiPSC)-derived RGC-rich retinal tissues using hypoxia-reoxygenation in vitro. Flow cytometry, immunochemistry, and Western blotting showed the apoptosis and necrosis of RGCs under hypoxia-reoxygenation, and they were rescued by an apoptosis inhibitor but not by a necrosis inhibitor. This revealed that the cell death induced in our model was mainly due to apoptosis. To our knowledge, this is the first model to reproduce ischemia-reperfusion in hiPSC-derived RGCs. Thus, the efficacy of apoptosis inhibitors and neuroprotective agents can be evaluated using this model, bringing us closer to clinical applications.

A chatbot to improve adherence to internet-based cognitive-behavioural therapy among workers with subthreshold depression: a randomised controlled trial.

BACKGROUND: Internet-based cognitive-behavioural therapy (iCBT) is effective for subthreshold depression. However, iCBT has problems with adherence, especially when unaccompanied by human guidance. Knowledge on how to enhance adherence to iCBT without human involvement can contribute to improving the effectiveness of iCBT. OBJECTIVE: This is an implementation study to examine the effect of an automated chatbot to improve the adherence rate of iCBT. METHODS: We developed a chatbot to increase adherence to an existing iCBT programme, and a randomised controlled trial was conducted with two groups: one group using iCBT plus chatbot (iCBT+chatbot group) and one group not using the chatbot (iCBT group). Participants were full-time employees with subthreshold depression working in Japan (n=149, age mean=41.4 (SD=11.1)). The primary endpoint was the completion rate of the iCBT programme at 8 weeks. FINDINGS: We analysed data from 142 participants for the primary outcome. The completion rate of the iCBT+chatbot group was 34.8% (24/69, 95% CI 23.5 to 46.0), that of the iCBT group was 19.2% (14/73, 95% CI 10.2 to 28.2), and the risk ratio was 1.81 (95% CI 1.02 to 3.21). CONCLUSIONS: Combining iCBT with a chatbot increased participants' iCBT completion rate. CLINICAL IMPLICATIONS: Encouraging messages from the chatbot could improve participation in an iCBT programme. Further studies are needed to investigate whether chatbots can improve adherence to the programme in the long term and to assess their impact on depression, anxiety and well-being. TRIAL REGISTRATION NUMBER: UMIN000047621.

Modeling long-term transfers of radiocesium in farmland under different tillage and cover crop treatments.

The 2011 nuclear accident at Japan's Fukushima Daiichi Nuclear Power Plant (FDNPP) prompted inquiries about the long-term transfer of Cesium-137 (137Cs) from soil to agricultural plants. In this context, numerical modeling is particularly useful for the long-term evaluation of the consequences of agroecosystem contamination. Agricultural practices, such as tillage and cover cropping, play key roles in 137Cs recycling in agroecosystems. In this study, we used 10-year monitoring data to develop a dynamic model to predict 137Cs redistribution (via uptake, litterfall, translocation, and percolation) under different tillage (no-tillage, NT; rotary cultivation, RC; moldboard plow, MP) and cover crop (rye; hairy vetch; fallow weed) treatments. The verification exercise and assessment results indicated the model's reliability, as the temporal dynamics of predicted values agreed with observed values. Tillage significantly influenced the 137Cs distribution in soil, thereby decreasing plant uptake of 137Cs, whereas cover crop exerted a minimal effect on 137Cs cycling. Furthermore, while the 137Cs concentrations in soybean grain under RC and NT treatments were comparable 62 years after the FDNPP accident, the concentration under MP treatment remained consistently the lowest. Despite natural decay being the main cause of the decreased global 137Cs level in the agroecosystem, with minimal losses from percolation to deeper soil layers and soybean harvesting, adopting an appropriate tillage practice was shown to promote a long-term reduction of 137Cs concentration in crops. Finally, to improve the model's accuracy, further research should consider incorporating the effects of soil properties and extreme weather events on 137Cs flow into the model, as these factors are essential for realizing improved agroecosystem predictions.

Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells.

Sex hormones, such as androgens and estrogens, are predominantly produced in the gonads (ovaries and testes) and adrenal cortex. Endocrine-disrupting chemicals (EDCs) are substances that mimic, block, or interfere with hormones in the endocrine systems of humans and organisms. EDCs mainly act via nuclear receptors and steroidogenesis-related enzymes. In the OECD conceptual framework for testing and assessment of EDCs, several well-known assays are used to identify the potential disruption of nuclear receptors both in vivo and in vitro, whereas the H295R steroidogenesis assay is the only assay that detects the disruption of steroidogenesis. Forskolin and prochloraz are often used as positive controls in the H295R steroidogenesis assay. Decamethylcyclopentasiloxane (D5) was suspected one of EDCs, but the effects of D5 on steroidogenesis remain unclear. To establish a short-term in vivo screening method that detects the disruption of steroidogenesis, rats in the present study were fed a diet containing forskolin, prochloraz, or D5 for 14 days. Forskolin increased plasma levels of 17ß-estradiol (E2) and testosterone as well as the mRNA level of Cyp19 in both the adrenal glands and ovaries. Prochloraz induced the loss of cyclicity in the sexual cycle and decreased plasma levels of E2 and testosterone. D5 increased E2 levels and shortened the estrous cycle in a dose-dependent manner; however, potential endocrine disruption was not detected in the H295R steroidogenesis assay. These results demonstrate the importance of comprehensively assessing the endocrine-disrupting effects of chemicals on steroidogenesis in vivo.

How dynamic transfer models can complement an equilibrium-based approach: Case studies of radiocesium transfer to forest trees following accidental atmospheric release.

Accidental release of radionuclides caused by nuclear accidents like those in Fukushima and Chernobyl can result in pulses of radioactivity entering the forest environment. Due to intense recycling in the forest, equilibrium between radioactivity concentrations in trees and in soil may not be reached during the period of short-term radionuclide transport following the accident. Another question arises as to whether the equilibrium hypothesis using empirical concentration ratios (CRs) can be applied to the long-term period. Using two atmospheric 137Cs fallout scenarios in the Fukushima and Chernobyl sites, this study investigated whether the CR approach could provide conservative predictions of 137Cs levels in trees following 137Cs fallout events by comparing predictions from the CR approach using data gathered for trees by the IAEA to those from dynamic transfer models and actual measured data. The inter-comparisons also aimed to investigate whether the CR approach could account for the variability of 137Cs levels across different tree organs. The results showed that caution may be necessary when using the CR approach, which relies on the IAEA dataset, to estimate 137Cs accumulation in forest trees in the short - and long term following atmospheric 137Cs fallout events. A calculation by TRIPS 2.0 demonstrated the importance of considering the distribution within tree organs for in-depth analysis of radiological impact of forest trees. Our findings suggest that it may be preferable to use CR values based on site-specific data rather than generic data collected from various sites. This is particularly relevant when studying the sites where the bioavailability of 137Cs for trees and thus possible exposures are higher. This study also showed that dynamic modeling approaches could offer an alternative means of estimating CR values of the entire tree or specific tree organs in situations where empirically derived values are not available.

Distinct features of two lipid droplets types in cell nuclei from patients with liver diseases.

Lipid droplets (LDs) have been observed in the nuclei of hepatocytes; however, their significance in liver disease remains unresolved. Our purpose was to explore the pathophysiological features of intranuclear LDs in liver diseases. We included 80 patients who underwent liver biopsies; the specimens were dissected and fixed for electron microscopy analysis. Depending on the presence of adjacent cytoplasmic invagination of the nuclear membrane, LDs in the nuclei were classified into two types: nucleoplasmic LDs (nLDs) and cytoplasmic LD invagination with nucleoplasmic reticulum (cLDs in NR). nLDs were found in 69% liver samples and cLDs in NR were found in 32%; no correlation was observed between the frequencies of the two LD types. nLDs were frequently found in hepatocytes of patients with nonalcoholic steatohepatitis, whereas cLDs in NR were absent from the livers of such patients. Further, cLDs in NR were often found in hepatocytes of patients with lower plasma cholesterol level. This indicates that nLDs do not directly reflect cytoplasmic lipid accumulation and that formation of cLDs in NR is inversely correlated to the secretion of very low-density lipoproteins. Positive correlations were found between the frequencies of nLDs and endoplasmic reticulum (ER) luminal expansion, suggesting that nLDs are formed in the nucleus upon ER stress. This study unveiled the presence of two distinct nuclear LDs in various liver diseases.

Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet.

The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.

Integrator complex subunit 15 controls mRNA splicing and is critical for eye development.

The eye and brain are composed of elaborately organized tissues, development of which is supported by spatiotemporally precise expression of a number of transcription factors and developmental regulators. Here we report the molecular and genetic characterization of Integrator complex subunit 15 (INTS15). INTS15 was identified in search for the causative gene(s) for an autosomal-dominant eye disease with variable individual manifestation found in a large pedigree. While homozygous Ints15 knockout mice are embryonic lethal, mutant mice lacking a small C-terminal region of Ints15 show ocular malformations similar to the human patients. INTS15 is highly expressed in the eye and brain during embryogenesis and stably interacts with the Integrator complex to support small nuclear RNA 3' end processing. Its knockdown resulted in missplicing of a large number of genes, probably as a secondary consequence, and substantially affected genes associated with eye and brain development. Moreover, studies using human iPS cells-derived neural progenitor cells showed that INTS15 is critical for axonal outgrowth in retinal ganglion cells. This study suggests a new link between general transcription machinery and a highly specific hereditary disease.

Poor Diagnostic Efficacy of Noninvasive Tests for Advanced Fibrosis in Obese or Younger Than 60 Diabetic NAFLD patients.

BACKGROUND & AIMS: Serum-based noninvasive tests (NITs) have been widely used to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). However, the diagnostic efficacy of NITs across ranges of age, body mass index (BMI), and presence of type 2 diabetes (T2DM) may vary and have not been well-characterized. METHODS: We analyzed 1489 patients with biopsy-proven NAFLD from 6 centers in Japan, Taiwan, and Korea. Using histology as the gold standard, we compared the areas under the receiver operating characteristic (AUROCs) of Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and the new Hepamet fibrosis score (HFS), with a focus on performance in subgroups as stratified by age, BMI, and the presence of T2DM. RESULTS: By histology, 44.0% of the overall cohort (655/1489) had F2-4, and 20.6% (307/1489) had F3-4 fibrosis. FIB-4 had the highest AUROCs for both F2-4 (0.701 vs NFS 0.676 and HFS 0.682, P = .001) and F3-4 (0.767 vs NFS 0.736 and HFS 0.752, P = .002). However, for F3-4 fibrosis, the AUROCs of all 3 NITs were generally higher in older (>60 years), nonobese (BMI <25 kg/m2), and non-diabetic patients, although overall the best performance was observed with FIB-4 among nonobese (BMI<25) diabetic patients (AUROC, 0.92). The worst performance was observed in younger patients with T2DM for all NITs including FIB-4 (AUROC, 0.63-0.66). CONCLUSIONS: FIB-4 had higher diagnostic efficacy for F3-4 than NFS or HFS, but this varied greatly by age, BMI, and T2DM, with better performance in older, nonobese, and nondiabetic patients. However, all NITs including FIB-4 had unacceptably poor performance in young or obese diabetic patients.

Effect of illness uncertainty on alanine transaminase levels and aspartate aminotransferase levels in patients with nonalcoholic fatty liver disease.

Patients with nonalcoholic fatty liver disease (NAFLD) have illness uncertainty. The purpose of this longitudinal study was to investigate the effect of the degree of illness uncertainty in patients with NAFLD on liver function values. We conducted a questionnaire survey and collected blood samples from outpatients with NAFLD. The items in the questionnaire were measured for illness uncertainty using the Japanese version of the Mishel Uncertainty in Illness Scale-Community (MUIS-C). Blood samples were collected at baseline and after 1 year. We divided the patients into two groups: one with high illness uncertainty and the other with low illness uncertainty. We then compared changes in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels over time from baseline using multiple regression analysis. This study analyzed 148 patients with NAFLD; 75 were male and 73 were female, with a mean age of 58.4 ± 12.3 years. The group with higher illness uncertainty had significantly higher ALT and AST levels at 1 year (ß = .185 and .183, respectively) than the group with lower illness uncertainty. High illness uncertainty in patients with NAFLD can lead to higher ALT and AST levels. Healthcare providers must focus on reducing illness uncertainty in patients with NAFLD.

Recovery From Severe Systemic Peripheral Neuropathy Secondary to Erythropoietic Protoporphyria by Liver Transplant: A Case Report.

Erythropoietic protoporphyria is a rare inherited metabolic disorder involving the heme biosynthesis pathway and leads to the accumulation of protoporphyrin in the erythrocytes or liver. Although peripheral neuropathy is known to develop occasionally in other types of porphyria, it rarely occurs in patients with erythropoietic protoporphyria. A 16-year-old boy was transferred to our hospital due to end-stage liver disease secondary to erythropoietic protoporphyria. Severe systemic peripheral neuropathy, similar to that presented in Guillain-Barré syndrome, developed; it was promptly managed with mechanical ventilation. Electrophysiological assessment of the presented neuropathy showed no responsiveness, indicating severe axonopathy. Six weeks after the transfer, liver transplant was performed.Postoperatively, hepatorenal syndromes improved immediately, and his erythrocyte protoporphyrin level decreased from 6291 to 174 µg/dL red blood cells.The patient started to move his limbs gradually and was weaned from mechanical ventilation 2 months after liver transplant. Eventually, he was discharged from hospital and was able to ambulate with assistance 10 months after liver transplant. To our knowledge, this is the first report detailing the clinical course in a patient with erythropoietic protoporphyria who recovered from severe systemic peripheral neuropathy after liver transplant.

Recycling and persistence of iodine 127 and 129 in forested environments: A modelling approach.

Differences in the source and behaviour of 129I compared to 127I isotopes have been described for a variety of surface environments, but little is known about the cycling rates of each isotope in terrestrial ecosystems. We developed a compartment model of the iodine cycle in a forest ecosystem, with a labile and non-labile pool to simplify the complex fate of iodine in the forest floor and soil. Simulations were performed using atmospheric 127I and 129I inputs for sites differing in climate, vegetation, and soil. In general, considering dry deposition in addition to wet deposition improved model simulations. Model results support the view that soil is the sink for atmospheric iodine deposited in forest ecosystems, while tree vegetation has little influence on long-term iodine budgets. Modelling also showed that iodine cycling reaches equilibrium after a period of about 5000 years, mainly due to a gradual incorporation of iodine into the bulk stabilised soil organic matter. At steady state, this pool of non-labile iodine in soil can retain about 20% of total deposition with a mean residence time of 900 years, while the labile iodine pool is renewed after 90 years. The proportions of modern anthropogenic 129I in each modelled pool reflect those of stable 127I at least several decades after input to the forest; this result explains why isotopic disequilibrium is common in field data analysis. Volatilisation plays a central role in regulating iodine storage in soil and, therefore, its residence time, while drainage is a minor export pathway, except at some calcareous sites. Dynamic modelling has been particularly helpful for gaining insight into the long-term response of iodine partitioning to continuous, single or even varying deposition. Our modelling study suggested that better estimates of dry deposition of atmospheric iodine, weathering of parent rock, and volatilisation of the deposited iodine from soil and vegetation will be required for reliable predictions of iodine cycling in specific forests, because these processes remain insufficiently explored.

Global and regional long-term survival following resection for HCC in the recent decade: A meta-analysis of 110 studies.

Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p = 0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p = 0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.

Dynamics of radiocaesium within forests in Fukushima-results and analysis of a model inter-comparison.

Forests cover approximately 70% of the area contaminated by the Fukushima Daiichi Nuclear Power Plant accident in 2011. Following this severe contamination event, radiocaesium (137Cs) is anticipated to circulate within these forest ecosystems for several decades. Since the accident, a number of models have been constructed to evaluate the past and future dynamics of 137Cs in these forests. To explore the performance and uncertainties of these models we conducted a model inter-comparison exercise using Fukushima data. The main scenario addressed an evergreen needleleaf forest (cedar/cypress), which is the most common and commercially important forest type in Japan. We also tested the models with two forest management scenarios (decontamination by removal of soil surface litter and forest regeneration) and, furthermore, a deciduous broadleaf forest (konara oak) scenario as a preliminary modelling study of this type of forest. After appropriate calibration, the models reproduced the observed data reliably and the ranges of calculated trajectories were narrow in the early phase after the fallout. Successful model performances in the early phase were probably attributable to the availability of comprehensive data characterizing radiocaesium partitioning in the early phase. However, the envelope of the calculated model end points enlarged in long-term simulations over 50 years after the fallout. It is essential to continue repetitive verification/validation processes using decadal data for various forest types to improve the models and to update the forecasting capacity of the models.

Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis.

Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-ß, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.

The protective effect of tight-fitting powered air-purifying respirators during chest compressions.

BACKGROUND: Airborne personal protective equipment is required for healthcare workers when performing aerosol-generating procedures on patients with infectious diseases. Chest compressions, one of the main components of cardiopulmonary resuscitation, require intense and dynamic movements of the upper body. We aimed to investigate the protective effect of tight-fitting powered air-purifying respirators (PAPRs) during chest compressions. METHODS: This single-center simulation study was performed from February 2021 to March 2021. The simulated workplace protection factor (SWPF) is the concentration ratio of ambient particles and particles inside the PAPR mask; this value indicates the level of protection provided by a respirator when subjected to a simulated work environment. Participants performed continuous chest compressions three times for 2 min each time, with a 4-min break between each session. We measured the SWPF of the tight-fitting PAPR during chest compression in real-time mode. The primary outcome was the ratio of any failure of protection (SWPF <500) during the chest compression sessions. RESULTS: Fifty-four participants completed the simulation. Overall, 78% (n = 42) of the participants failed (the measured SWPF value was less than 500) at least one of the three sessions of chest compressions. The median value and interquartile range of the SWPF was 4304 (685-16,191). There were no reports of slipping down of the respirator or mechanical failure during chest compressions. CONCLUSIONS: Although the median SWPF value was high during chest compressions, the tight-fitting PAPR did not provide adequate protection.

Quality of Life in patients with nonalcoholic fatty liver disease: Structure and related factors focusing on illness uncertainty.

AIM: Patients with nonalcoholic fatty liver disease (NAFLD) have a low quality of life (QOL) and illness uncertainty. This study examined the structure of QOL and associated factors, including illness uncertainty, among individuals with NAFLD. METHODS: A cross-sectional survey was conducted using a self-administered questionnaire for outpatients with NAFLD. QOL was measured using the Short Form-8. Dietary habits, physical activity level, illness uncertainty, health locus of control, and knowledge of NAFLD were assessed. Path analysis was used to study the associated factors of QOL and their structure, including uncertainty of disease. RESULTS: Path analysis of 168 NAFLD patients indicated that a high Physical Component Summary score on the Short Form-8-representing physical QOL-was predicted by a body mass index <25 kg/m2 and high educational level. A high Mental Component Summary score-representing mental QOL-was predicted by being male, good dietary habits, low illness uncertainty, and presence of consultants. The model showed satisfactory goodness-of-fit without being rejected by the chi-square test (goodness-of-fit index = .947, adjusted goodness-of-fit index = .917, comparative fit index = .967, root mean square error of approximation = 0.023). CONCLUSIONS: Nurses need to work closely with NAFLD patients as consultants, providing adequate information about the causes, treatments, and dietary habits, and focusing on the individual's perception of health. This could reduce illness uncertainty and contribute to the improvement of QOL.

The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040.

BACKGROUND: NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD. METHODS: We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD-8 studies) patients. RESULTS: The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983-2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD. CONCLUSION: NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.