Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

The use of fractional radiofrequency in Asian patients to improve skin texture.

BACKGROUND AND OBJECTIVES: Fractional radiofrequency devices have been demonstrated to improve skin texture, such as smoothness, rhytides, brightness, and atrophic acne scars, by increasing dermal thickness, dermal collagen content, and dermal fibrillin content. The objective of the study is to assess the efficacy and adverse effects of this device on Asian patients of skin type III and IV with skin textural changes. MATERIALS AND METHODS: The study was designed as a prospective, open-labeled single-arm study, which was conducted with 20 Chinese patients aged 21-60 years and having irregularities in their skin texture, rhytides, and acne scars. The patients received six treatments at intervals of 4 weeks. Treatment was initiated with the maximum energy tolerated, which was then adjusted during the course of treatment if the patients felt excessive discomfort. A total of two passes were delivered in each session. Physician assessment results and standardized photographs were collected at the baseline, after all treatment visits, and at 1, 2, and 6 months after the final treatment visit. RESULTS: A total of 17 patients completed the study according to the established protocol. At the 6-month follow-up, 71% of patients were satisfied and 24% of patients were very satisfied with the received treatments, and the treatment physician reported varying degrees of improvement based on the global assessment scale in 60% of the subjects. While the anticipated side effects, such as erythema, edema, pinpoint bleeding, scab formation, and flare of acne, were noted in the patients, no serious adverse effects occurred. CONCLUSION: The use of fractional radiofrequency improves skin texture and is safe for use in Asian patients of skin type III and IV. No long-term serious adverse effects were noted.

Impact of carbohydrate quantity and quality on maternal and pregnancy outcomes in gestational diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the impact of carbohydrate quantity and quality on maternal and pregnancy outcomes in gestational diabetes mellitus. METHODS: Using a pre-defined search strategy, two researchers systematically searched MEDLINE, CINAHL Plus, and PubMed for randomized controlled trials comparing low-carbohydrate, low-glycaemic index, or low-glycaemic load diets with usual care in gestational diabetes mellitus. Mean differences and risk ratios were extracted. RESULTS: Thirteen studies with 877 participants were included. Low-carbohydrate diet did not significantly differ from usual care for fasting blood glucose (3 studies; mean difference: 1.60 mmol/L; 95 % confidence interval: -1.95, 5.15), insulin requirement (2 studies; risk ratio: 1.01; 95 % confidence interval: 0.31, 3.05), birthweight (4 studies; mean difference: -0.23 kg; 95 % confidence interval: -1.90, 1.45), caesarean delivery (5 studies; risk ratio: 1.11; 95 % confidence interval: 0.66, 1.85), macrosomia (3 studies; risk ratio: 0.35; 95 % confidence interval: 0.00, 2130.64), large-for-gestational-age (2 studies; risk ratio: 0.46; 95 % confidence interval: 0.03, 7.20), and small-for-gestational-age infants (2 studies; risk ratio: 0.94; 95 % confidence interval: 0.00, 231.18). Low-glycaemic index diet did not significantly differ from usual care for the above outcomes either. However, low-glycaemic load diet reduced macrosomia risk (2 studies; risk ratio: 0.51; 95 % confidence interval: 0.43, 0.59). CONCLUSIONS: Low-carbohydrate and low-glycaemic index diets do not differ from usual care for most maternal and foetal outcomes in gestational diabetes mellitus. But low-glycaemic load diet may reduce macrosomia risk.

Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species.

In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6+ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+ LYVE1+ cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206+ macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+ peritoneal cells, which, in turn, resembled human peritoneal CD1c+CD14-CD64- cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.

SON is an essential m6A target for hematopoietic stem cell fate.

Stem cells regulate their self-renewal and differentiation fate outcomes through both symmetric and asymmetric divisions. m6A RNA methylation controls symmetric commitment and inflammation of hematopoietic stem cells (HSCs) through unknown mechanisms. Here, we demonstrate that the nuclear speckle protein SON is an essential m6A target required for murine HSC self-renewal, symmetric commitment, and inflammation control. Global profiling of m6A identified that m6A mRNA methylation of Son increases during HSC commitment. Upon m6A depletion, Son mRNA increases, but its protein is depleted. Reintroduction of SON rescues defects in HSC symmetric commitment divisions and engraftment. Conversely, Son deletion results in a loss of HSC fitness, while overexpression of SON improves mouse and human HSC engraftment potential by increasing quiescence. Mechanistically, we found that SON rescues MYC and suppresses the METTL3-HSC inflammatory gene expression program, including CCL5, through transcriptional regulation. Thus, our findings define a m6A-SON-CCL5 axis that controls inflammation and HSC fate.

Steatosis drives monocyte-derived macrophage accumulation in human metabolic dysfunction-associated fatty liver disease.

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear. Methods: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. Mouse models of hepatic steatosis were used to investigate observations made from human liver tissue. Results: We observed variable degrees of liver steatosis with minimal fibrosis in our participants. Single-cell RNA sequencing revealed four macrophage clusters that exist in the human fatty liver encompassing Kupffer cells and monocyte-derived macrophages (MdMs). The genes expressed in these macrophage subsets were similar to those observed in mouse models of MAFLD. Hepatic CD14+ monocyte/macrophage number correlated with the degree of steatosis. Using mouse models of early liver steatosis, we demonstrate that recruitment of MdMs precedes Kupffer cell loss and liver damage. Electron microscopy of isolated macrophages revealed increased lipid accumulation in MdMs, and ex vivo lipid transfer experiments suggested that MdMs may serve a distinct role in lipid uptake during MAFLD. Conclusions: The human liver in MAFLD contains macrophage subsets that align well with those that appear in mouse models of fatty liver disease. Recruited myeloid cells correlate well with the degree of liver steatosis in humans. MdMs appear to participate in lipid uptake during early stages of MALFD. Impact and implications: Metabolic dysfunction associated fatty liver disease (MAFLD) is extremely common; however, the early inflammatory responses that occur in human disease are not well understood. In this study, we investigated macrophage heterogeneity in human livers during early MAFLD and demonstrated that similar shifts in macrophage subsets occur in human disease that are similar to those seen in preclinical models. These findings are important as they establish a translational link between mouse and human models of disease, which is important for the development and testing of new therapeutic approaches for MAFLD.

Financial well-being as a mediator of the relationship between multimorbidity and health-related quality of life in people with cancer.

BACKGROUND: It is unknown whether financial well-being mediates the impact of multimorbidity on the health-related quality of life (HRQoL) of cancer patients. METHODS: Participants were recruited from three outpatient oncology clinics of Hong Kong public hospitals. Multimorbidity was assessed using the Charlson Comorbidity Index. Financial well-being, the mediator of the association between multimorbidity and HRQoL outcomes, was assessed using the Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. The HRQoL outcomes were assessed using the Functional Assessment of Cancer Therapy - General (FACT-G) and its four sub-dimensions. Mediation analyses were conducted using SPSS PROCESS v4.1. RESULTS: Six-hundred and forty cancer patients participated in the study. Multimorbidity had a direct effect on FACT-G scores independent of financial well-being (ß for path c' = -0.752, p < 0.001). In addition, multimorbidity had an indirect effect on FACT-G scores through its effect on financial well-being (ß for path a = -0.517, p < 0.05; ß for path b = 0.785, p < 0.001). Even after adjustments were made for the covariates, the indirect effect of multimorbidity on FACT-G via financial well-being remained significant, accounting for 38.0% of the overall effect, indicating partial mediation. Although there were no statistically significant associations between multimorbidity, social well-being, and emotional well-being, the indirect effects of multimorbidity on physical and functional well-being through financial well-being remained significant. CONCLUSIONS: Poor financial well-being attributable to multimorbidity partially mediates the direct impact of chronic conditions on HRQoL in Chinese cancer patients, particularly their physical and functional well-being.

RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells.

Tissue homeostasis is maintained after stress by engaging and activating the hematopoietic stem and progenitor compartments in the blood. Hematopoietic stem cells (HSCs) are essential for long-term repopulation after secondary transplantation. Here, using a conditional knockout mouse model, we revealed that the RNA-binding protein SYNCRIP is required for maintenance of blood homeostasis especially after regenerative stress due to defects in HSCs and progenitors. Mechanistically, we find that SYNCRIP loss results in a failure to maintain proteome homeostasis that is essential for HSC maintenance. SYNCRIP depletion results in increased protein synthesis, a dysregulated epichaperome, an accumulation of misfolded proteins and induces endoplasmic reticulum stress. Additionally, we find that SYNCRIP is required for translation of CDC42 RHO-GTPase, and loss of SYNCRIP results in defects in polarity, asymmetric segregation, and dilution of unfolded proteins. Forced expression of CDC42 recovers polarity and in vitro replating activities of HSCs. Taken together, we uncovered a post-transcriptional regulatory program that safeguards HSC self-renewal capacity and blood homeostasis.

Emotional subtypes in patients with depression: A cluster analysis.

Major depressive disorder (MDD) is associated with deficits in emotion experience, expression and regulation. Whilst emotion regulation deficits prolong MDD, emotion expression influences symptomatic presentations, and anticipatory pleasure deficits predict recurrence risk. Profiling MDD patients from an emotion componential perspective can characterize subtypes with different clinical and functional outcomes. This study aimed to investigate emotional subtypes of MDD. A two-stage cluster analysis applied to 150 MDD patients. Clustering variables included emotion experience measured by Temporal Experience of Pleasure Scale, emotion expression measured by Toronto Alexithymia Scale, and emotion regulation measured by Emotion Regulation Questionnaire. We validated the resultant clusters by comparing their symptoms and functioning with that of 50 controls. Cluster 1 (n = 50) exhibited intact emotion experience and expression yet adopted reappraisal rather than suppression strategy, whereas Cluster 2 (n = 66) exhibited generalized emotional deficits. Cluster 3 (n = 34) exhibited emotion expression deficits and adopted both reappraisal and suppression strategies. On validation, Cluster 2 exhibited the worst, but Cluster 1 exhibited the least symptoms and social functioning impairments. Cluster 3 was intermediate among the two other subtypes. Our findings support the existence of different emotional subtypes in MDD patients, and have clinical and theoretical implications for developing future specific treatments for MDD.

Video feedback to update negative self-perceptions in social anxiety disorder: A comparison of internet-delivered vs face-to-face cognitive therapy formats.

BACKGROUND: Video feedback is a technique used in cognitive therapy for social anxiety disorder (CT-SAD) to update patients' negative self-perceptions of how they appear to others. Clients are supported to watch video of themselves engaging in social interactions. While typically undertaken in session with a therapist, this study aimed to investigate the effectiveness of remotely delivered video feedback embedded within an Internet-based cognitive therapy program (iCT-SAD). METHODS: We examined patients' self-perceptions and social anxiety symptoms before and after video feedback in two randomised controlled trials. Study 1 compared 49 iCT-SAD participants with 47 from face-to-face CT-SAD. Study 2 was a replication using data from 38 iCT-SAD participants from Hong Kong. RESULTS: In Study 1, ratings of self-perceptions and social anxiety showed significant reductions following video feedback, in both treatment formats. 92 % of participants in iCT-SAD, and 96 % in CT-SAD thought they looked less anxious compared to their predictions after viewing the videos. The change in self-perception ratings was larger in CT-SAD compared to iCT-SAD, but there was no evidence that the impact of video feedback on social anxiety symptoms around a week later differed between the two treatments. Study 2 replicated the iCT-SAD findings of Study 1. LIMITATIONS: The level of therapist support in iCT-SAD videofeedback varied with clinical need and was not measured. CONCLUSIONS: The findings indicate that video feedback can be delivered effectively online, and that its impact on social anxiety is not significantly different from in-person treatment delivery.

Dual IKZF2 and CK1α degrader targets acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is a hematologic malignancy for which several epigenetic regulators have been identified as therapeutic targets. Here we report the development of cereblon-dependent degraders of IKZF2 and casein kinase 1α (CK1α), termed DEG-35 and DEG-77. We utilized a structure-guided approach to develop DEG-35 as a nanomolar degrader of IKZF2, a hematopoietic-specific transcription factor that contributes to myeloid leukemogenesis. DEG-35 possesses additional substrate specificity for the therapeutically relevant target CK1α, which was identified through unbiased proteomics and a PRISM screen assay. Degradation of IKZF2 and CK1α blocks cell growth and induces myeloid differentiation in AML cells through CK1α-p53- and IKZF2-dependent pathways. Target degradation by DEG-35 or a more soluble analog, DEG-77, delays leukemia progression in murine and human AML mouse models. Overall, we provide a strategy for multitargeted degradation of IKZF2 and CK1α to enhance efficacy against AML that may be expanded to additional targets and indications.

Mitochondrial Pyruvate Carrier Inhibition Attenuates Hepatic Stellate Cell Activation and Liver Injury in a Mouse Model of Metabolic Dysfunction-associated Steatotic Liver Disease.

Hepatic stellate cells (HSC) are non-parenchymal liver cells that produce extracellular matrix comprising fibrotic lesions in chronic liver diseases. Prior work demonstrated that mitochondrial pyruvate carrier (MPC) inhibitors suppress HSC activation and fibrosis in a mouse model of metabolic dysfunction-associated steatohepatitis (MASH). In the present study, pharmacologic or genetic inhibition of the MPC in HSC decreased expression of markers of activation in vitro. MPC knockdown also reduced the abundance of several intermediates of the TCA cycle, and diminished α-ketoglutarate played a key role in attenuating HSC activation by suppressing hypoxia inducible factor-1α signaling. On high fat diets, mice with HSC-specific MPC deletion exhibited reduced circulating transaminases, numbers of HSC, and hepatic expression of markers of HSC activation and inflammation compared to wild-type mice. These data suggest that MPC inhibition modulates HSC metabolism to attenuate activation and illuminate mechanisms by which MPC inhibitors could prove therapeutically beneficial for treating MASH.

Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma.

Primary liver cancer (PLC) includes hepatocellular carcinoma and intrahepatic cholangiocarcinoma and is the sixth most common cancer worldwide with poor prognosis. PLC is characterized by an abundant stromal reaction in which cancer-associated fibroblasts (CAFs) are one of the major stromal components. Solid evidence has demonstrated the crucial role of CAFs in tumor progression, and CAF abundance is often correlated with poor clinical outcomes. Although CAFs are regarded as an attractive and promising target for PLC treatment, a poor understanding of CAF origins and heterogeneity and a lack of specific CAF markers are the major hurdles to efficient CAF-specific therapy. In this review, we examine recent advances in the understanding of CAF diversity in the context of biomarkers, subtypes, and functions in PLC. The regulatory roles of CAFs in extracellular matrix remodeling, metastasis, cancer stemness, and therapeutic resistance are summarized. With an increasing link between CAF abundance and reduced antitumor immune responses, we provide updated knowledge on the crosstalk between CAFs and immune cells within the tumor microenvironment, which leads to immune resistance. In addition, we present current CAF-targeted therapies and describe some future perspectives. A better understanding of CAF biology will shed light on a novel therapeutic strategy against PLC.

Success Rate of Transcranial Doppler Scanning of Cerebral Arteries at Different Transtemporal Windows in Healthy Elderly Individuals.

This study measured the rates of success in applying transcranial Doppler (TCD) scanning at the middle, posterior and anterior temporal windows (MTW, PTW and ATW) in the elderly. A hand-held 1.6-MHz pulsed-wave TCD transducer was used to search for cerebral arteries at MTW, PTW and ATW locations. Physical attributes of the head, including head circumference and the distance between tragi on both sides ("tragus-to-tragus arc length"), were also measured to explore the associations with successful rates. Among 396 healthy elderly participants (aged 62.6 ± 6.0 y, 140 men), 81.1% (n = 321; 127 men) had one or more temporal windows penetrable by TCD ultrasound (n = 286 [72.2%] at MTW, n = 195 [49.2%] at PTW and n = 106 [26.8%] at ATW). Regression analysis revealed that successful scanning increased significantly in male participants at three window locations. Younger age significantly increased successful scanning at the MTW and ATW. Smaller tragus-to-tragus arc length increased successful scanning at the MTW, but unsuccessful scanning at the ATW. Our findings support using MTW as the first location when positioning the TCD transducer for the scanning of cerebral arteries in the elderly population. When performing TCD scanning on two temporal windows, we propose choosing the MTW and PTW.

A case of recurrent systemic capillary leak syndrome triggered by influenza A infection associated with cardiogenic shock supported by veno-arterial extracorporeal membrane oxygenation.

Systemic capillary leak syndrome (SCLS) is a rare and under-recognized disease which is potentially fatal. We report a case of SCLS triggered by influenza A infection associated with fulminant cardiogenic shock, successfully supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Strong clinical suspicion with appropriate supportive treatment can be life-saving for patients with SCLS.

Dietary lipids inhibit mitochondria transfer to macrophages to divert adipocyte-derived mitochondria into the blood.

Adipocytes transfer mitochondria to macrophages in white and brown adipose tissues to maintain metabolic homeostasis. In obesity, adipocyte-to-macrophage mitochondria transfer is impaired, and instead, adipocytes release mitochondria into the blood to induce a protective antioxidant response in the heart. We found that adipocyte-to-macrophage mitochondria transfer in white adipose tissue is inhibited in murine obesity elicited by a lard-based high-fat diet, but not a hydrogenated-coconut-oil-based high-fat diet, aging, or a corn-starch diet. The long-chain fatty acids enriched in lard suppress mitochondria capture by macrophages, diverting adipocyte-derived mitochondria into the blood for delivery to other organs, such as the heart. The depletion of macrophages rapidly increased the number of adipocyte-derived mitochondria in the blood. These findings suggest that dietary lipids regulate mitochondria uptake by macrophages locally in white adipose tissue to determine whether adipocyte-derived mitochondria are released into systemic circulation to support the metabolic adaptation of distant organs in response to nutrient stress.

Audiovisual temporal processing in adult patients with first-episode schizophrenia and high-functioning autism.

Schizophrenia and autism spectrum disorder (ASD) are both neurodevelopmental disorders with altered sensory processing. Widened temporal binding window (TBW) signifies reduced sensitivity to detect stimulus asynchrony, and may be a shared feature in schizophrenia and ASD. Few studies directly compared audiovisual temporal processing ability in the two disorders. We recruited 43 adult patients with first-episode schizophrenia (FES), 35 average intelligent and verbally-fluent adult patients with high-functioning ASD and 48 controls. We employed two unisensory Temporal Order Judgement (TOJ) tasks within visual or auditory modalities, and two audiovisual Simultaneity Judgement (SJ) tasks with flash-beeps and videos of syllable utterance as stimuli. Participants with FES exhibited widened TBW affecting both speech and non-speech processing, which were not attributable to altered unisensory sensory acuity because they had normal visual and auditory TOJ thresholds. However, adults with ASD exhibited intact unisensory and audiovisual temporal processing. Lower non-verbal IQ was correlated with larger TBW width across the three groups. Taking our findings with earlier evidence in chronic samples, widened TBW is associated with schizophrenia regardless illness stage. The altered audiovisual temporal processing in ASD may ameliorate after reaching adulthood.

Internet-delivered cognitive therapy for social anxiety disorder in Hong Kong: A randomized controlled trial.

Background: Research is needed to determine the extent to which internet-delivered psychological therapies are effective when delivered in countries and cultures outside of where they were developed. Objective: This waitlist-controlled study evaluated the efficacy of a UK-developed, therapist-guided internet Cognitive Therapy programme for Social Anxiety Disorder (iCT-SAD) when delivered in Hong Kong by local therapists. Methods: Patients were randomized to iCT-SAD (n = 22) or a waitlist control group (n = 22). Assessments took place at weeks 0, 8, and 15 (posttreatment/postwait), with a further 3-month follow-up assessment for the iCT-SAD group. The primary outcome measure was the Liebowitz Social Anxiety Scale (self-report), and posttreatment/postwait diagnostic assessments were completed by independent assessors blind to condition. Trial Registration: ISRCTN11357117. Results: Compared with the waitlist group, iCT-SAD significantly reduced social anxiety symptoms (adjusted difference at posttreatment 55.36, 95%CI 44.32 to 66.39, p < 0.001; d Cohen 2.41). The treatment was also superior to waitlist on all secondary outcome measures. 86% of the iCT-SAD group demonstrated remission from SAD based on the LSAS, compared to 5% of the waitlist group. 73% no longer met diagnostic criteria at posttreatment, compared to 9% of the waitlist group. The gains made by the iCT-SAD group were maintained at three-month follow-up. Conclusions: iCT-SAD showed strong efficacy for the treatment of SAD in Hong Kong. As the clinical outcomes were similar to UK studies, this suggests the dissemination of the treatment into a different cultural setting did not result in a substantial loss of efficacy.

Comprehensive analysis of liver macrophage composition by flow cytometry and immunofluorescence in murine NASH.

Recently, it has become evident that macrophage diversity increases in the liver during the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we provide a detailed protocol for the analysis of liver macrophage subsets in mice with non-alcoholic fatty liver disease (NAFLD) and early NASH using flow cytometry and immunofluorescence (IF). These methods can be used to assess the composition and localization of macrophage subsets during NASH. For complete details on the use and execution of this protocol, please refer to Daemen et al. (2021).