Exploring Vaccine Hesitancy and Uptake during COVID-19: A Review of PM's Mann Ki Baat Dialogue.

Public health programmes are interlinked and intertwined with communication, advocacy and social mobilisation for their success. The unprecedented situation created by COVID-19 brought a medical emergency all over the world, the like of which was probably not seen after the Spanish Flu outbreak, a century ago. First there seemed no solution in sight when tens of thousands of people lost their lives to the coronavirus in various countries, but when the vaccine arrived, there were, in general, doubts about its efficacy and safety. Indian scenario was not any different. When the government launched the vaccine in a campaign mode in January 2021, it was also battling with misperceptions and vaccine hesitancy. Prime Minister Narendra Modi took it upon himself to address the issue through his various addresses to the nation and his signature programme Mann ki Baat (MKB) on the radio. This review paper examines the empirical research on MKB coverage of the COVID-19 pandemic, the media multiplier impact of the MKB, people's voices through their engagement with various social media platforms, and what is the impact on vaccine uptake.

Upregulation of Taurine Biosynthesis and Bile Acid Conjugation with Taurine through FXR in a Mouse Model with Human-like Bile Acid Composition.

Taurine, the end product in the sulfur-containing amino acid pathway, is conjugated with bile acids (BAs) in the liver. The rate-limiting enzymes in both taurine synthesis and BA conjugation may be regulated by a nucleus receptor, FXR, that promotes BA homeostasis. However, it is controversial because BAs act as natural FXR agonists or antagonists in humans and mice, respectively, due to the species differences in BA synthesis. The present study evaluated the influences of different BA compositions on both pathways in the liver by comparing Cyp2a12-/-/Cyp2c70-/- mice with a human-like BA composition (DKO) and wild-type (WT) mice. The DKO liver contains abundant natural FXR agonistic BAs, and the taurine-conjugated BA proportion and the taurine concentration were significantly increased, while the total BA concentration was significantly decreased compared to those in the WT liver with natural FXR antagonistic BAs. The mRNA expression levels of the enzymes Bacs and Baat in BA aminations and Cdo and Fmo1 in the taurine synthesis, as well as Fxr and its target gene, Shp, were significantly higher in the DKO liver than in the WT liver. The present study, using a model with a human-like BA composition in the liver, confirmed, for the first time in mice, that both the taurine synthesis and BA amidation pathways are upregulated by FXR activation.

A Dual Coverage Monitoring of the Bile Acids Profile in the Liver-Gut Axis throughout the Whole Inflammation-Cancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis.

Hepatocellular carcinoma (HCC) is the terminal phase of multiple chronic liver diseases, and evidence supports chronic uncontrollable inflammation being one of the potential mechanisms leading to HCC formation. The dysregulation of bile acid homeostasis in the enterohepatic circulation has become a hot research issue concerning revealing the pathogenesis of the inflammatory-cancerous transformation process. We reproduced the development of HCC through an N-nitrosodiethylamine (DEN)-induced rat model in 20 weeks. We achieved the monitoring of the bile acid profile in the plasma, liver, and intestine during the evolution of "hepatitis-cirrhosis-HCC" by using an ultra-performance liquid chromatography-tandem mass spectrometer for absolute quantification of bile acids. We observed differences in the level of primary and secondary bile acids both in plasma, liver, and intestine when compared to controls, particularly a sustained reduction of intestine taurine-conjugated bile acid level. Moreover, we identified chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, and glycolithocholic acid in plasma as biomarkers for early diagnosis of HCC. We also identified bile acid-CoA:amino acid N-acyltransferase (BAAT) by gene set enrichment analysis, which dominates the final step in the synthesis of conjugated bile acids associated with the inflammatory-cancer transformation process. In conclusion, our study provided comprehensive bile acid metabolic fingerprinting in the liver-gut axis during the inflammation-cancer transformation process, laying the foundation for providing a new perspective for the diagnosis, prevention, and treatment of HCC.

The association between liver fibrosis scores and chronic kidney disease.

Purpose: This study aimed to clarify the relationship between liver fibrosis scores (Fibrosis-4, BARD score, and BAAT score) and chronic kidney disease (CKD). Methods: We collected a range of data from 11,503 subjects (5,326 men and 6,177 women) from the rural regions of Northeastern China. Three liver fibrosis scores (LFSs) including fibrosis-4 (FIB-4), BARD score, and BAAT score were adopted. A logistic regression analysis was used to calculate odds ratios and the 95% confidence interval. A subgroup analysis showed the association between LFSs and CKD under different stratifications. Restricted cubic spline could further explore whether there is a linear relationship between LFSs and CKD. Finally, we used C-statistics, Net Reclassification Index (NRI), and Integrated Discrimination Improvement (IDI) to assess the effect of each LFS on CKD. Results: Through the baseline characteristics, we observed that LFSs were higher in the CKD population than in non-CKD. The proportion of participants with CKD also increased with LFSs. In a multivariate logistic regression analysis, the ORs of CKD were 6.71 (4.45-10.13) in FIB-4, 1.88 (1.29-2.75) in the BAAT score, and 1.72 (1.28-2.31) in the BARD score by comparing the high level with the low level in each LFSs. Moreover, after adding LFSs to the original risk prediction model, which consisted of age, sex, drinking, smoking, diabetes, low-density lipoprotein cholesterol, total cholesterol, triglycerides, and mean waist circumference, we found the new models have higher C-statistics. Furthermore, NRI and IDI both indicate LFSs had a positive effect on the model. Conclusions: Our study showed that LFSs are associated with CKD among middle-aged populations in rural areas of northeastern China.

Association analysis for SNPs of BAAT and COL1A1 genes with cashmere production performance and other production traits in Liaoning cashmere goats.

This study aimed to investigate the relationship between the polymorphism of bile acid-CoA: amino acid N-acyltransferase (BAAT) and collagen type I alpha 1 chain (COL1A1) genes and the production performance of Liaoning Cashmere goat (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence comparison of BAAT and COL1A1 genes and PCR-Seq polymorphism, and the effect of SNPs on production performance was analyzed by SPSS software. The results showed that three SNPs loci were detected in BAAT gene: G7900A, T7967C, C7998T, and one SNP locus T6716C was detected in COL1AL gene. At G7900A locus, the dominant genotype for cashmere performance was GG, and the dominant genotype for body measurement traits and milk production traits was AG. At T7967C locus, the dominant genotype for cashmere performance was TT, and the dominant genotype for body measurement traits and milk production traits was CC. At C7998T locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. At the T6716C locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. H1H1: AACC is the dominant haplotype combination. Therefore, this study will provide a reliable reference for future research on cashmere production performance, body measurement traits, and milk production traits of LCG.

Involvement of B-aat1 and Cbs in regulating mantle pigmentation in the Pacific oyster (Crassostrea gigas).

BACKGROUND: Shell color formation is an important physiological process in bivalves, the molecular genetic basis has potential application in bivalve aquaculture, but there is still remaining unclear about this issue. The cystine/glutamate transporter (Slc7a11) and cystathionine beta-synthase (Cbs) are integral genes in pheomelanin synthesis pathway, which is vital to skin pigmentation. METHODS AND RESULTS: Here, the sequences of b (0, +) -type amino acid transporter 1 (B-aat1) and Cbs in Pacific oyster (Crassostrea gigas) (CgB-aat1, CgCbs) were characterized. Phylogenetically, the deduced amino acid sequences of CgB-aat1 and CgCbs both possessed conserved features. Genes were both ubiquitously expressed in six tested tissues with more abundant expression level in central mantle. Besides, the polyclonal antibodies of CgB-aat1, CgCbs, CgTyr, and CgTyrp2 were successfully prepared. Immunofluorescence analysis revealed that CgB-aat1 and CgCbs proteins were both expressed in gill rudiments of eyed-larvae and concentrated mainly in cytoplasm of epithelial cell and nerve axons in mantle. Additionally, after CgB-aat1 or CgCbs silencing, expressions at mRNA and protein levels of CgB-aat1 and CgCbs involved in pheomelanin synthesis were significantly suppressed, and CgTyr, CgTyrp1 and CgTyrp2 related to eumelanin synthesis were also down-regulated but no apparent differences, respectively. Moreover, micrographic examination found less brown-granules at mantle edge in CgB-aat1 interference group. CONCLUSION: These results implied that pheomelanin synthesis was possible induced by CgB-aat1-CgTyr-CgCbs axis, and it played an essential role on mantle pigmentation in the oysters. These findings provide the useful genetic knowledge and enrich the physiological information for the shell color formation in bivalve aquaculture.

Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation.

Bile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4α (HNF4α) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7α-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4α levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.

Impact of liver fibrosis score on the incidence of stroke: A cohort study.

PURPOSE: The purpose was to explore the value of liver fibrosis scores (fibrosis-4, BAAT score and BARD score) for incidence risk of stroke in a cohort study. METHODS: A total of 9088 participants without stroke history enrolled the follow-up. Three liver fibrosis scores (LFSs) including FIB-4, BARD score and BAAT score were adopted. The end point was stroke. Cox regression analysis was used to calculate hazard ratios and 95% confidence interval. Kaplan-Meier curve was used to show the probability of stoke in different levels of LFSs. Subgroup analysis showed the association between LFSs and stroke under different stratification. Restricted cubic spline could further explore whether there is a linear relationship between LFSs and stroke. Finally, we used C-statistics, Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) to assess the discriminatory power of each LFS for stroke. RESULTS: During a median follow-up time of 4.66 years, 272 participants had a stroke. Through the baseline characteristics, we observed that the stroke incidence population tends to be male and older. It was shown by Kaplan-Meier that three LFSs were associated with stroke and high levels of LFSs significantly increase the probability of stroke. In the univariate Cox regression analysis, the HR of stroke risk was 6.04 (4.14-8.18) in FIB-4, 2.10 (1.45-3.04) in BAAT score and 1.81 (1.38-2.38) in BARD score by comparing the high level with the low level at each LFSs. The adjusted HRs for three LFSs were 2.05 (1.33-3.15) in FIB-4, 1.61 (1.10-2.35) in BAAT score and 1.54 (1.17-2.04) in BARD score by comparing the high group with low group. We found that multivariable-adjusted HRs of three LFSs still increased for stroke when stratified by various factors in subgroup analysis. Moreover, after adding LFSs to original risk prediction model which consist of age, sex, drinking, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, total cholesterol and triglycerides, we found that new models have higher C-statistics of stroke. Furthermore, we calculated Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) to show the ability of LFSs to predict stroke. CONCLUSIONS: Our study showed that three LFSs were associated with stroke amongst middle-aged populations in rural areas of Northeast China. Furthermore, it suggests that LFSs can be used as a risk stratification tool to predict stroke.

Potent suppression of hydrophobic bile acids by aldafermin, an FGF19 analogue, across metabolic and cholestatic liver diseases.

BACKGROUND & AIMS: Higher serum bile acid levels are associated with an increased risk of cirrhosis and liver-related morbidity and mortality. Herein, we report secondary analyses of aldafermin, an engineered analogue of the gut hormone fibroblast growth factor 19, on the circulating bile acid profile in prospective, phase II studies in patients with metabolic or cholestatic liver disease. METHODS: One hundred and seventy-six patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis and elevated liver fat content (≥8% by magnetic resonance imaging-proton density fat fraction) received 0.3 mg (n = 23), 1 mg (n = 49), 3 mg (n = 49), 6 mg (n = 28) aldafermin or placebo (n = 27) for 12 weeks. Sixty-two patients with primary sclerosing cholangitis (PSC) and elevated alkaline phosphatase (>1.5× upper limit of normal) received 1 mg (n = 21), 3 mg (n = 21) aldafermin or placebo (n = 20) for 12 weeks. Serum samples were collected on day 1 and week 12 for determination of bile acid profile and neoepitope-specific N-terminal pro-peptide of type III collagen (Pro-C3), a direct measure of fibrogenesis. RESULTS: Treatment with aldafermin resulted in significant dose-dependent reductions in serum bile acids. In particular, bile acids with higher hydrophobicity indices, such as deoxycholic acid, lithocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, and glycocholic acid, were markedly lowered by aldafermin in both NASH and PSC populations. Moreover, aldafermin predominantly suppressed the glycine-conjugated bile acids, rather than the taurine-conjugated bile acids. Changes in levels of bile acids correlated with changes in the novel fibrogenesis marker Pro-C3, which detects a neo-epitope of the type III collagen during its formation, in the pooled NASH and PSC populations. CONCLUSIONS: Aldafermin markedly reduced major hydrophobic bile acids that have greater detergent activity and cytotoxicity. Our data provide evidence that bile acids may contribute to sustaining a pro-fibrogenic microenvironment in the liver across metabolic and cholestatic liver diseases. LAY SUMMARY: Aldafermin is an analogue of a gut hormone, which is in development as a treatment for patients with chronic liver disease. Herein, we show that aldafermin can potently and robustly suppress the toxic, hydrophobic bile acids irrespective of disease aetiology. The therapeutic strategy utilising aldafermin may be broadly applicable to other chronic gastrointestinal and liver disorders. CLINICAL TRIALS REGISTRATION: The study is registered at Clinicaltrials.govNCT02443116 and NCT02704364.

Performance of Noninvasive Liver Fibrosis Scores in the Morbid Obese Patient, Same Scores but Different Thresholds.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. It is a spectrum of progressive alterations, with the final step in liver fibrosis which carries a high burden of long-term mortality. The scores used to predict liver fibrosis are not properly validated in morbid obesity (MO). Our aim was to evaluate the performance of seven risk scores in bariatric surgery (BS) patients. METHODS: Cross-sectional analysis in a cohort of 60 patients with MO undergoing BS. Liver biopsy (LB) was taken and compared with fibrosis risk assessed by noninvasive scores: APRI, FIB-4, Forns, NFS (NAFLD fibrosis score), BARD, BAAT, and Hepamet. The area under the receiver operator characteristic curve (AUROC) and measures of diagnostic accuracy were calculated; performance of fibrosis scores was evaluated at standard threshold vs those suggested by ROC analysis. RESULTS: LB was available in 50 patients; 9 (18%) had significant fibrosis (F2-F4). The BARD and Forns scores best predicted the absence of fibrosis, both with negative predictive value (NPV) of 95.5%, with AUROC of 0.761 and 0.667, respectively. Modification of standard thresholds (2 for BARD and 6.9 for Forns) to those suggested by ROC analysis (3 and 3.6, respectively) improved performance of scores. Basal glucose, glycated hemoglobin (HbA1c), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) were identified by logistic regression analysis as independent predictor of fibrosis. CONCLUSIONS: Existing scoring systems are unable to stratify fibrosis risk in MO using established thresholds; its performance is improved if these cutoffs are modified.

Histological Evaluation of Non-alcoholic Fatty Liver Disease and Its Correlation with Different Noninvasive Scoring Systems with Special Reference to Fibrosis: A Single Center Experience.

BACKGROUND: Although liver biopsy remains the gold standard for the diagnosis of non-alcoholic fatty liver disease [NAFLD], many non-invasive markers of liver fibrosis have recently been proposed and assessed as surrogates of liver biopsy. AIMS AND OBJECTIVE: To evaluate the degree of liver fibrosis by different non-invasive fibrosis scoring systems and to compare each non-invasive fibrosis scoring system with histological fibrosis stage. MATERIALS AND METHODS: The study population consists of consecutive patients with biopsy proven NAFLD. Complete medical history was taken and physical examination was done in all patients along with appropriate biochemical evaluations. NAFLD fibrosis score, BARD score, BAAT score and APRI score were calculated and each score was compared with histological fibrosis staging. RESULTS: The study population consisted of 60 patients having mean age 39.73 years (SD 9.62, range 17-63 years) including 51 (85%) males and 9 (15%) females. On histology fibrosis was present in 68.3% (41/60) patients. Out of 60 patients 41 had fibrosis and among them 17, 22, 2 patients had grade 1, 2, 3 fibrosis respectively and no one had grade 4 fibrosis. 61.67% (37/60) had definite NASH. Comparing the fibrosis of histology with the noninvasive scoring systems, the sensitivity and specificity of NAFLD fibrosis score were 5.56% and 100% respectively. BARD score had 45.83% sensitivity and 80.55% specificity. The sensitivities of BAAT score and APRI score were 0% and 29.16% respectively and the specificities were 100% and 97.22% respectively. CONCLUSION: The noninvasive scoring systems like NFS, BARD, BAAT, and APRI are not sensitive enough to detect fibrosis but highly specific to include fibrosis if scores are more than cut-off values in our cohort, however they cannot replace liver biopsy. Newer more efficient non-invasive scoring systems have to be devised for the Indian NAFLD population.

Bile acid nuclear receptor FXR and digestive system diseases.

Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.

Role of farnesoid X receptor and bile acids in alcoholic liver disease.

Alcoholic liver disease (ALD) is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR) and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a) and PPARα (peroxisome proliferator-activated receptor alpha) in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.

11ß-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice.

11ß-Hydroxysteroid dehydrogenase-1 (11ß-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11ß-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specific and global 11ß-HSD1-deficient mice. 11ß-HSD1-deficiency resulted in elevated circulating unconjugated BAs, an effect more pronounced in global than liver-specific knockout mice. Gene expression analyses revealed decreased expression of the BA-CoA ligase Fatp5, suggesting impaired BA amidation. Reduced organic anion-transporting polypeptide-1A1 (Oatp1a1) and enhanced organic solute-transporter-ß (Ostb) mRNA expression were observed in livers from global 11ß-HSD1-deficient mice. The impact of 11ß-HSD1-deficiency on BA homeostasis seems to be GR-independent because intrahepatic corticosterone and GR target gene expression were not substantially decreased in livers from global knockout mice. Moreover, Fatp5 expression in livers from hepatocyte-specific GR knockout mice was unchanged. The results revealed a role for 11ß-HSD1 in BA homeostasis.

Toxicity and intracellular accumulation of bile acids in sandwich-cultured rat hepatocytes: role of glycine conjugates.

Excessive intrahepatic accumulation of bile acids (BAs) is a key mechanism underlying cholestasis. The aim of this study was to quantitatively explore the relationship between cytotoxicity of BAs and their intracellular accumulation in sandwich-cultured rat hepatocytes (SCRH). Following exposure of SCRH (on day-1 after seeding) to various BAs for 24h, glycine-conjugated BAs were most potent in exerting toxicity. Moreover, unconjugated BAs showed significantly higher toxicity in day-1 compared to day-3 SCRH. When day-1/-3 SCRH were exposed (0.5-4h) to 5-100µM (C)DCA, intracellular levels of unconjugated (C)DCA were similar, while intracellular levels of glycine conjugates were up to 4-fold lower in day-3 compared to day-1 SCRH. Sinusoidal efflux was by far the predominant efflux pathway of conjugated BAs both in day-1 and day-3 SCRH, while canalicular BA efflux showed substantial interbatch variability. After 4h exposure to (C)DCA, intracellular glycine conjugate levels were at least 10-fold higher than taurine conjugate levels. Taken together, reduced BA conjugate formation in day-3 SCRH results in lower intracellular glycine conjugate concentrations, explaining decreased toxicity of (C)DCA in day-3 versus day-1 SCRH. Our data provide for the first time a direct link between BA toxicity and glycine conjugate exposure in SCRH.

Prevalence and associated metabolic factors of fatty liver disease in the elderly.

OBJECTIVE: The aim of this study was to investigate the metabolic risk factors for fatty liver disease in the elderly, and determine the prevalence of fatty liver disease in the elderly in Wuhan, central China. METHODS: The study was a case-control study based on all 4226 adults above 60 years of age from a cohort investigated in 2010-11 at the medical examination center of Zhongnan hospital, using 3145 randomly selected adults under 60 years of age from the same cohort as controls. Fatty liver disease (FLD) was identified with ultrasound imaging. The risk factors measured were body mass index (BMI), and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low density lipoprotein (LDL) and serum uric acid (SUA). The probability of steatohepatitis with advanced fibrosis was predicted using a score based on BMI, age, ALT, and TG (BAAT),and using AST/ALT ratio (AAR). RESULTS: FLD was higher in the elderly (26.7%) than in the non-elderly (22.8%) and similar in the elderly between men and women (26.6% vs 27.0%, p>0.05). BMI, TC, TG, LDL, SUA, AST and ALT were all significantly higher in FLD, whereas the level of HDL was markedly lower. Multiple regression analyses showed that obesity, high TC, TG, SUA, low HDL, and elevated ALT, AAR<1 were closely related to the elderly FLD, while male sex, obesity, high TC, TG, low HDL, elevated ALT, AST and AAR<1 were closely related to the non-elderly FLD. The prevalence of steatohepatitis with advanced fibrosis estimated as BAAT index≥3 was 2.4% in all subjects, and was higher in the elderly FLD patients than in the non-elderly FLD patients. CONCLUSION: The prevalence of FLD is higher in the elderly, and is broadly related to the same metabolic risk factors as in the non-elderly. However, female-sex is no longer protective with increasing age, and the prevalence of steatohepatitis with advanced fibrosis is estimated to be considerably higher in the elderly FLD patients than in the non-elderly FLD controls.

Regulation of ATM/DNA-PKcs Phosphorylation by BRCA1-Associated BAAT1.

BRCA1 has been implicated in the DNA damage pathway and regulation of genome stability, however, it does not contain intrinsic catalytic activity to repair the DNA lesions. Thus, a potential activity of BRCA1 is to assemble proteins that sense DNA damage and to transduce checkpoint signals to downstream. We have recently isolated a protein termed BAAT1, which binds to BRCA1, ATM, DNA-PKcs, and SMC1. Phosphorylation of ATM/DNA-PKcs is greatly reduced in BAAT1-knockdown cells, suggesting that sensing of DNA lesions mediated by BRCA1/BAAT1 is critical for activation of these kinases.