Dynamic change of MASLD in chronic hepatitis C patients after viral eradication: A nationwide registry study in Taiwan.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1C (6.0% vs. 5.9%, P<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, P<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, P<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, P<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (P=0.17). Body mass index (BMI) (odds ratio [OR]/95% confidence intervals [CI]: 0.89/0.85-0.92, P<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR/CI: 1.10/1.06-1.14, P<0.001) and HbA1c (OR/CI: 1.19/1.04-1.35, P=0.01), were independently associated with MASLD development after HCV cure. Conclusions: HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

Comparing similarities and differences between NAFLD, MAFLD, and MASLD in the general U.S. population.

Background: Recently, the multisociety Delphi consensus renamed non-alcoholic fatty liver disease (NAFLD) terminology [previously renamed metabolic-associated fatty liver disease (MAFLD)] as metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to compare the similarities and differences between NAFLD, MAFLD, and MASLD and to clarify the impact of this new name change. Methods: A cross-sectional study of 3,035 general subjects with valid vibration-controlled transient elastography data was conducted based on data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. NAFLD, MAFLD, and MASLD were defined according to the corresponding consensus criteria. Results: Using controlled attenuation parameter (CAP) ≥274 dB/m and liver stiffness measurements (LSM) ≥9.7 kPa as the cutoff values for the presence of hepatic steatosis and advanced liver fibrosis (ALF), the prevalence of NAFLD, MAFLD, and MASLD were 38.01% (95% CI 35.78-40.29%), 41.09% (39.09-43.12%), and 37.9% (35.70-40.14%), respectively, and the corresponding prevalence of ALF was 10.21% (7.09-14.48%), 10.13% (7.06-14.35%), and 10.24% (7.11-14.53%), respectively. The kappa values for the three definitions were above 0.9. The prevalence and severity of the three definitions remained similar when the sensitivity analyses were performed using different CAP thresholds. The prevalence of NAFLD, MAFLD, MASLD, and ALF increased as the number of cardiometabolic risk factors (CMRF) increased. Conclusions: Our findings highlight the consistency among the three definitions, especially between NAFLD and MASLD, so that the new consensus will not disturb the original NAFLD-related findings. Additionally, more attention should be paid to patients with a high number of CMRFs.

An herbal formula Shenlian decoction upregulates M1/M2 macrophage proportion in hepatocellular carcinoma by suppressing complement cascade.

The immunosuppressive microenvironment is a vital factor for the hepatocellular carcinoma (HCC) progression. However, effective treatment is lacking at current. Shenlian decoction (SLD) is a registered herbal therapy for the HCC treatment, but the underlying mechanism of SLD remains largely elusive. Here, we aimed to explore the anti-tumor effect of SLD in the treatment of HCC. SLD was intragastrically given after the tumor initiation in ß-catenin/C-Met or DEN and CCl4 induced HCC mouse model. The tumor growth levels were evaluated by liver weight and histological staining. The tumor-infiltrating immune cells were detected by immunological staining and flow cytometry. The mechanism of the SLD was detected by non-targeted proteomics and verified by a cell co-culture system. The result showed that SLD significantly attenuated HCC progression. SLD promoted macrophage infiltration and increased the M1/M2 macrophage ratio within the tumor tissues. Non-targeted proteomics showed the inhibition of complement C5/C5a signaling is the key mechanism of SLD. Immunological staining showed SLD inhibited C5/C5a expression and C5aR1+ macrophage infiltration. The suggested mechanism was demonstrated by application of C5aR1 inhibitor, PMX-53 in mouse HCC model. Hepatoma cell-macrophage co-culture showed SLD targeted hepatoma cells and inhibited the supernatant-induced macrophage M2 polarization. SLD inhibited AMPK/p38 signaling which is an upstream mechanism of C5 transcription. In conclusion, we found SLD relieved immune-suppressive environment by inhibiting C5 expression. SLD could suppress the C5 secretion in hepatoma cells via inhibition of AMPK/p38 signaling. We suggested that SLD is a potential herbal therapy for the treatment of HCC by alleviating immune-suppressive status.

Fibrosis and steatotic liver disease in US adolescents according to the new nomenclature.

OBJECTIVE: To apply the new nomenclature for steatotic liver diseases (SLD), replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD), in adolescents using National Health and Nutrition Examination Survey (NHANES) data. METHODS: Among 1410 adolescents (12-19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa). Obesity and alanine aminotransferase (ALT) ≥ 80 U/L were used to identify adolescents qualifying for hepatology referral according to practice guidelines. NAFLD was defined as liver steatosis without a specific exposure; it has no cardiometabolic risk factor requirement, unlike MASLD. RESULTS: Steatosis (yes/no) is the first decision point in the new diagnostic protocol; however, criteria for steatosis are undefined. At the supplier (EchoSens)-recommended CAP threshold of 240 dB/m, 30.5% (95% confidence interval [CI]: 27.1%-34.0%) of adolescents had SLD and about 85% of adolescents with NAFLD met criteria for MASLD. The other 15% would receive an ambiguous diagnosis of either cryptogenic SLD or possible MASLD. At higher CAP thresholds, MASLD/NAFLD concordance increased and approached 100%. Among adolescents with MASLD-fibrosis, only 8.8% (95% CI: 0%-19.3%) had overweight/obese and ALT ≥ 80 U/L. CONCLUSIONS: The new nomenclature highlights the high prevalence of liver steatosis. At the CAP threshold of 240 dB/m, however, approximately 15% of adolescents would receive an ambiguous diagnosis, which could lead to confusion and worry. Fewer than 10% of adolescents with MASLD-fibrosis had overweight/obese and ALT ≥ 80 U/L. Revised guidelines are needed to ensure that the other 90% receive appropriate referral and liver disease care.

Influence of different position modal parameters on milling chatter stability of orthopedic surgery robots.

This research is dedicated to exploring the dynamics of milling chatter stability in orthopedic surgery robots, focusing on the impact of position modal parameters on chatter stability. Initially, we develop a dynamic milling force model for the robotic milling process that integrates both modal coupling and regenerative effects. We then employ the zero-order frequency domain method to derive a chatter stability domain model, visually represented through stability lobe diagrams (SLDs). Through conducting hammer test experiments, we ascertain the robot's modal parameters at varying positions, enabling the precise generation of SLDs. This study also includes experimental validation of the chatter SLD analysis method, laying the groundwork for further examination of chatter stability across different positional modal parameters. Finally, our analysis of the variations in modal parameters on the stability of robot milling chatter yields a theoretical framework for optimizing cutting parameters and developing control strategies within the context of orthopedic surgery robots.

Innovative technologies for the fabrication of 3D/4D smart hydrogels and its biomedical applications - A comprehensive review.

Repairing and regenerating damaged tissues or organs, and restoring their functioning has been the ultimate aim of medical innovations. 'Reviving healthcare' blends tissue engineering with alternative techniques such as hydrogels, which have emerged as vital tools in modern medicine. Additive manufacturing (AM) is a practical manufacturing revolution that uses building strategies like molding as a viable solution for precise hydrogel manufacturing. Recent advances in this technology have led to the successful manufacturing of hydrogels with enhanced reproducibility, accuracy, precision, and ease of fabrication. Hydrogels continue to metamorphose as the vital compatible bio-ink matrix for AM. AM hydrogels have paved the way for complex 3D/4D hydrogels that can be loaded with drugs or cells. Bio-mimicking 3D cell cultures designed via hydrogel-based AM is a groundbreaking in-vivo assessment tool in biomedical trials. This brief review focuses on preparations and applications of additively manufactured hydrogels in the biomedical spectrum, such as targeted drug delivery, 3D-cell culture, numerous regenerative strategies, biosensing, bioprinting, and cancer therapies. Prevalent AM techniques like extrusion, inkjet, digital light processing, and stereo-lithography have been explored with their setup and methodology to yield functional hydrogels. The perspectives, limitations, and the possible prospects of AM hydrogels have been critically examined in this study.

Genetic risk accentuates dietary effects on hepatic steatosis, inflammation and fibrosis in a population-based cohort.

BACKGROUND & AIMS: Steatotic liver disease (SLD), characterized by elevated liver fat content (LFC), is influenced by genetics and diet. However, whether diet has a differential effect based on genetic risk is not well-characterized. We aimed to determine how genetic factors interact with diet to affect SLD in a large national biobank. METHODS: We included UK Biobank participants with dietary intake measured by 24-hour recall and genotyping. The primary predictors were dietary pattern, PNPLA3-rs738409-G, TM6SF2-rs58542926-T, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions. The primary outcome was LFC, and secondary outcomes were iron-controlled T1 time (cT1, a measure of liver inflammation and fibrosis) and liver-related events/mortality. RESULTS: A total of 21,619 participants met inclusion criteria. In non-interaction models, Mediterranean diet and intake of fruit/vegetables/legumes and fish associated with lower LFC, while higher red/processed meat intake and all genetic predictors associated with higher LFC. In interaction models, all genetic predictors interacted with Mediterranean diet and fruit/vegetable/legume intake, while the steatosis PRS interacted with fish intake and the TM6SF2 genotype interacted with red/processed meat intake, to affect LFC. Dietary effects on LFC were up to 3.8-fold higher in PNPLA3-rs738409-GG vs. -CC individuals, and 1.4-3.0-fold higher in the top vs. bottom quartile of the steatosis PRS. Gene-diet interactions were stronger in participants with vs. without overweight. The steatosis PRS interacted with Mediterranean diet and fruit/vegetable/legume intake to affect cT1 and most dietary and genetic predictors associated with risk of liver-related events or mortality by age 70. CONCLUSIONS: Effects of diet on LFC and cT1 were markedly accentuated in patients at increased genetic risk for SLD, implying dietary interventions may be more impactful in these populations. IMPACT AND IMPLICATIONS: Genetic variants and diet both influence risk of hepatic steatosis, inflammation/fibrosis, and hepatic decompensation; however, how gene-diet interactions influence these outcomes has previously not been comprehensively characterized. We investigated this topic in the community-based UK Biobank and found that genetic risk and dietary quality interacted to influence hepatic steatosis and inflammation/fibrosis on liver MRI, so that the effects of diet were greater in people at elevated genetic risk. These results are relevant for patients and medical providers because they show that genetic risk is not fixed (i.e. modifiable factors can mitigate or exacerbate this risk) and realistic dietary changes may result in meaningful improvement in liver steatosis and inflammation/fibrosis. As genotyping becomes more routinely used in clinical practice, patients identified to be at high baseline genetic risk may benefit even more from intensive dietary counseling than those at lower risk, though future prospective studies are required.

Steatotic Liver Disease and Sepsis Outcomes-A Prospective Cohort Study (SepsisFAT).

Background: While it has been shown that steatotic liver disease (SLD) is associated with systemic changes in immune response, the impact of SLD on sepsis outcomes has not yet been established. The aim of this study was to investigate the association between SLD and sepsis severity and outcomes. Methods: A prospective observational study included consecutively hospitalized adult patients with community-acquired sepsis during a 16-month period. Results: Of the 378 included patients (49.5% male, median age of 69, IQR 57-78 years), 174 (46%) were diagnosed with SLD. Patients with SLD were older and more frequently fulfilled the criteria for metabolic syndrome. There were no differences in the source and etiology of sepsis between the groups. Patients with SLD exhibited a higher incidence of acute kidney injury (29.3% vs. 17.6%), the need for renal replacement therapy (16.1% vs. 8.8%), and more frequent use of invasive mechanical ventilation (29.3% vs. 18.1%). In-hospital mortality was significantly higher in the SLD group (18.39% vs. 9.8%). The multivariable analysis indicated that SLD was associated with mortality (HR 2.82, 95% CI 1.40-5.71) irrespective of the other elements within metabolic syndrome. Conclusions: SLD might be associated with higher sepsis in-hospital mortality, and more frequent development of acute kidney and respiratory insufficiency requiring more critical care support.

Effects of Egg Consumption on Subjects with SLD or Hypertension: A MICOL Study.

BACKGROUND: Steatotic liver disease (SLD) is defined as a fat accumulation in more than 5% of hepatocytes; it can progress to non-alcoholic steatohepatitis (NASH), associated with an increased state of inflammation. The aim of this study was to explore the protective effects of eating eggs and any association with SLD and hypertension (HTN). METHODS: The study cohort included 908 participants assessed in the fourth recall of the MICOL study, grouped into four groups, based on NALFD and/or HTN. RESULTS: The prevalence of HTN and SLD among participants was 31.61%. Overall, the results indicated a statistical significance of egg consumption, showing a protective role against the two disease conditions, in both the raw and adjusted models (RRR = 0.34, p = 0.009, 0.15 to 0.76 95% C.I.). CONCLUSIONS: Many differences were found among the groups, and the protective role of eating eggs was amply demonstrated. We can conclude that it is unwise to demonize the intake of this food and its nutritional properties, in contrast with previous reports in the literature.

BI-3231, an enzymatic inhibitor of HSD17B13, reduces lipotoxic effects induced by palmitic acid in murine and human hepatocytes.

17-ß-hydroxysteroid dehydrogenase 13 (HSD17B13), a lipid droplet-associated enzyme, is primarily expressed in the liver and plays an important role in lipid metabolism. Targeted inhibition of enzymatic function is a potential therapeutic strategy for treating steatotic liver disease (SLD). The present study is aimed at investigating the effects of the first selective HSD17B13 inhibitor, BI-3231, in a model of hepatocellular lipotoxicity using human cell lines and primary mouse hepatocytes in vitro. Lipotoxicity was induced with palmitic acid in HepG2 cells and freshly isolated mouse hepatocytes and the cells were coincubated with BI-3231 to assess the protective effects. Under lipotoxic stress, triglyceride (TG) accumulation was significantly decreased in the BI-3231-treated cells compared with that of the control untreated human and mouse hepatocytes. In addition, treatment with BI-3231 led to considerable improvement in hepatocyte proliferation, cell differentiation, and lipid homeostasis. Mechanistically, BI-3231 increased the mitochondrial respiratory function without affecting ß-oxidation. BI-3231 inhibited the lipotoxic effects of palmitic acid in hepatocytes, highlighting the potential of targeting HSD17B13 as a specific therapeutic approach in steatotic liver disease.NEW & NOTEWORTHY 17-ß-Hydroxysteroid dehydrogenase 13 (HSD17B13) is a lipid droplet protein primarily expressed in the liver hepatocytes. HSD17B13 is associated with the clinical outcome of chronic liver diseases and is therefore a target for the development of drugs. Here, we demonstrate the promising therapeutic effect of BI-3231 as a potent inhibitor of HSD17B13 based on its ability to inhibit triglyceride accumulation in lipid droplets (LDs), restore lipid metabolism and homeostasis, and increase mitochondrial activity in vitro.

Concordance between metabolic dysfunction-associated steatotic liver disease and nonalcoholic fatty liver disease.

AIM: A multisociety consensus group proposed a new nomenclature for metabolic dysfunction-associated steatotic liver disease (MASLD). Although patients with nonalcoholic fatty liver disease (NAFLD) are expected to be reclassified as patients with MASLD under the new nomenclature, the concordance between MASLD and NAFLD remains unclear. Moreover, waist circumference could be adjusted by ethnicity for diagnosing MASLD; however, there are limited data on the optimal waist circumference in the Japanese population. METHODS: This cross-sectional study was conducted on 3709 Japanese patients with NAFLD. The primary endpoint was the prevalence of MASLD in patients with NAFLD. The difference between the original waist circumference criteria (>94 cm for men and >80 cm for women) and the Japanese metabolic syndrome criteria (≥85 cm for men and ≥90 cm for women) for concordance between NAFLD and MASLD was also investigated. RESULTS: According to the original criteria, the prevalence of MASLD in patients with NAFLD was 96.7%. Similarly, according to the Japanese waist circumference criteria, 96.2% of patients with NAFLD could be reclassified as those with MASLD. The concordance rate was significantly higher in the original criteria than in the Japanese criteria (p = 0.02). CONCLUSIONS: NAFLD could be considered MASLD using the original MASLD criteria in the Japanese population, and insights from NAFLD research could be applied to MASLD.

IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.

Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate in vitro that incubation with IL-32ß protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.

Derivation and validation of Transform equations to convert historical Enhanced liver fibrosis (ELF) scores to modern equivalents.

BACKGROUND AND AIMS: The Siemens Healthineers ELF™ Test was designed in 2004 with 2 algorithms to allow choice in histological alignment. Consequently, historical and modern algorithms are not fully harmonized, complicating comparisons involving early datasets. We derived transform equations to equate all ELF score versions, allowing historical data to be used in systematic reviews and meta-analyses. METHODS: Historical ELF equations were graphed pairwise versus their modern equivalent to assess correlation and derive four transforms. Transforms were validated using multiple datasets and evaluated for median absolute bias, number of samples reflecting clinically significant bias, number of discordant samples, bias at established cutoffs, and regression slope and y-intercept. RESULTS: Three transforms were validated equating Scheuer-aligned and/or age-included historical ELF equations (Immuno 1) to later equations aligned to Ishak and omitting age. A fourth transform corrected ADVIA Centaur® / Atellica® IM ELF scores miscalculated using the Scheuer Immuno 1 equation. Transformed data were well within allowable ELF bias limits. CONCLUSIONS: All transforms enabled accurate comparison of ELF scores generated by all historical algorithms to the current ADVIA Centaur / Atellica IM Analyzer ELF score. The transforms presented in this report should be used in systematic reviews and meta-analyses to facilitate comparisons to historical data.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

DONSON: Slding in 2 the limelight.

For over a decade, it has been known that yeast Sld2, Dpb11, GINS and Polε form the pre-loading complex (pre-LC), which is recruited to a CDC45-bound MCM2-7 complex by the Sld3/Sld7 heterodimer in a phospho-dependent manner. Whilst functional orthologs of Dbp11 (TOPBP1), Sld3 (TICRR) and Sld7 (MTBP) have been identified in metazoans, controversy has surrounded the identity of the Sld2 ortholog. It was originally proposed that the RECQ helicase, RECQL4, which is mutated in Rothmund-Thomson syndrome, represented the closest vertebrate ortholog of Sld2 due to a small region of sequence homology at its N-Terminus. However, there is no clear evidence that RECQL4 is required for CMG loading. Recently, new findings suggest that the functional ortholog of Sld2 is actually DONSON, a replication fork stability factor mutated in a range of neurodevelopmental disorders characterised by microcephaly, short stature and limb abnormalities. These studies show that DONSON forms a complex with TOPBP1, GINS and Polε analogous to the pre-LC in yeast, which is required to position the GINS complex on the MCM complex and initiate DNA replication. Taken together with previously published functions for DONSON, these observations indicate that DONSON plays two roles in regulating DNA replication, one in promoting replication initiation and one in stabilising the fork during elongation. Combined, these findings may help to uncover why DONSON mutations are associated with such a wide range of clinical deficits.

The Intellectual Profile of Adults with Specific Learning Disabilities.

Despite growing research on adults with specific learning disabilities (SLDs), evidence concerning their intellectual profile remains scarce. The present study examined the results of the administration of the Wechsler Adult Intelligence Scale-Fourth Edition to 301 adults diagnosed with SLDs and compared them to the results obtained from previous studies with a large sample of children with SLDs. The results showed that: (1) as observed among children, adults with SLDs also presented higher scores in the subtests implying reasoning (associated with the General Ability Index, GAI) and lower scores in the subtests involving working memory and processing speed; (2) the discrepancy between full-scale IQ and the GAI had a good predictive value in discriminating adults with and without SLDs; (3) the four-factor hierarchical structure of intelligence proposed for the general adult population held for adults with SLDs as well, even though there were substantial differences in the loadings and a five-factor structure could be more appropriate; (4) similarities as well as strong differences were present between adults and children with SLDs. In adults, scores on subtests were generally lower, particularly in working memory and processing speed. However, in some cases, scores were equal or even higher (as in the "Similarity" subtest) among adults, meaning that the discrepancy between the full scale and the GAI was accentuated.

Cognitive Profile Discrepancies among Typical University Students and Those with Dyslexia and Mixed-Type Learning Disorder.

BACKGROUND: Previous studies have identified areas of cognitive weakness in children diagnosed with Specific Learning Disorder (SLD), in the areas of working memory and processing speed in particular. In adulthood, this literature is still scant, and no studies have compared the cognitive profile of university students with dyslexia (DD) with that of students with Mixed-type SLD. METHOD: Thus, in this study, the WAIS-IV was used to examine the cognitive functioning of three groups of university students: students with DD, with Mixed-type SLD, and typical students. Statistical analyses were performed to examine differences in WAIS-IV FSIQ, main, and additional indexes and subtests. RESULTS: The results showed strengths in perceptual reasoning and good verbal comprehension abilities in both the DD and Mixed-type SLD group, with weaknesses in working memory and processing speed, leading to a pattern of a better General Ability Index (GAI) than Cognitive Proficiency Index (CPI) in both clinical groups. Thus, discrepancies between GAI and CPI, well documented in children with SLD, still manifest in adulthood in university students. Our findings also revealed worse cognitive performance in university students with mixed learning disorder relative to students with only a reading deficit. CONCLUSIONS: The cognitive features and distinctive subtest profiles that emerged should guide the assessment and the definitions of intervention programs, special educational needs, and strategies of compensation.

Strengths and Difficulties among Adolescent with and without Specific Learning Disorders (SLD).

Specific Learning Disorders (SLD) have become a major concern in modern societies. It is essential to detect their emotional, behavioral and social consequences as early as childhood. The aim of this study is to examine a set of strengths and difficulties and compare them between students with and without SLD. Participants in this study were adolescents aged 11-18 years from Budapest and villages of its Metropolitan area (Hungary) (N = 276, mean age = 13.6 years, SD = 1.8, 54.7% boys). Due to multistage sampling, a nearly equal number of students had SLD or not. In addition to sociodemographics, the Strengths and Difficulties Questionnaire (SDQ), Satisfaction With Life Scale and the Proactive Coping Inventory were included in the survey, and t-test, correlation and logistic regression analysis were applied in statistical analyses. Our findings suggest that in early adolescence (ages 11-14 years), conduct and peer problems, in late adolescence (ages 15-18 years), emotional problems, highlighted SLD. In terms of strengths, prosocial behavior in children with SLD may compensate difficulties, especially at a younger age. Students from lower SES families and those having parents with a lower educational level are more likely to have a diagnosis of SLD. Teachers and special educators should take care of improving the adolescents' prosociality, social and coping skills and listening to emotional, conduct and peer problems in those with SLD.