The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options

Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency

Creatine transporter deficiency (CTD), a leading cause of intellectual disability is a result of the mutation in the gene encoding the creatine transporter SLC6A8, which prevents creatine uptake into the brain, causing mental retardation, expressive speech and language delay, autistic-like behavior and epilepsy. Preclinical in vitro and in vivo data indicate that dodecyl creatine ester (DCE) which increases the creatine brain content, might be a therapeutic option for CTD patients. To gain a better understanding of the pathophysiology and DCE treatment efficacy in CTD, this study focuses on the identification of biomarkers related to cognitive improvement in a Slc6a8 knockout mouse model (Slc6a8−/y) engineered to mimic the clinical features of CTD patients which have low brain creatine content. Shotgun proteomics analysis of 4,035 proteins in four different brain regions; the cerebellum, cortex, hippocampus (associated with cognitive functions) and brain stem, and muscle as a control, was performed in 24 mice. Comparison of the protein abundance in the four brain regions between DCE-treated intranasally Slc6a8−/y mice and wild type and DCE-treated Slc6a8−/y and vehicle group identified 14 biomarkers, shedding light on the mechanism of action of DCE. Integrative bioinformatics and statistical modeling identified key proteins in CTD, including KIF1A and PLCB1. The abundance of these proteins in the four brain regions was significantly correlated with both the object recognition and the Y-maze tests. Our findings suggest a major role for PLCB1, KIF1A, and associated molecules in the pathogenesis of CTD

[In Press] Cultivating mindfulness : evaluation of a community-based mindfulness program for Arabic-speaking women in Australia

Arabic-speaking communities in Australia underutilise mental health services. Previous research with Arabic-speakers recruited individually demonstrated that an Arabic Mindfulness Compact Disc (CD) was an acceptable and useful resource for this group. Subsequently, the CD was introduced as part of a 5-week group mindfulness program for Arabic-speaking Muslim women. The intervention was delivered in a community setting by a bilingual (Arabic/English) psychologist with support from a bilingual multicultural health worker. The mixed-methods evaluation incorporated a pre–post study with a wait-list control group. An Arabic translation of the Depression Anxiety and Stress Scale (DASS21) was administered at baseline and program completion. Pre–post differences were tested using the sign test for paired samples (one-sided). Qualitative methods were used to evaluate the program’s acceptability. After five weeks, the intervention group showed statistically significant improvement on all DASS21 subscales (n = 12, p < .001 for depression and stress and p < .01 for anxiety). For the wait-list control group, only anxiety showed significant improvement (n = 8, p < .05). Qualitative analysis revealed how the women grew in their understanding of mindfulness concepts and mastered the different techniques, how they dealt with painful memories, how mindfulness practice assisted them in their daily lives, and how they related mindfulness to Islam. The in-language mindfulness intervention was shown to be culturally and spiritually relevant, and clinically effective. The group program incorporating the Arabic Mindfulness CD has potential for scaling up. Further research is required to investigate effectiveness for Arabic-speaking men with similar backgrounds

Dodecyl Creatine Ester Improves Cognitive Function and Identifies Drivers of Creatine Deficiency

Abstract Creatine transporter deficiency prevents creatine uptake into the brain, leading to mental retardation. To better understand the pathophysiology, this study focuses on the identification of biomarkers related to cognitive improvement in a Slc6a8 knockout mouse model (Slc6a8/y) engineered to mimic the clinical features of CTD patients which have low brain creatine content. Shotgun proteomics analysis of 4,035 proteins in four different brain regions; the cerebellum, cortex, hippocampus (associated with cognitive functions) and brain stem, and muscle as a control, was performed in 24 mice. Comparisons of the protein abundance in the four brain regions between DCE-treated intranasally Slc6a8-/y mice and wild type and DCE-treated Slc6a8-/y and vehicle group identified 14 biomarkers, shedding light on the mechanism of action of DCE. Integrative bioinformatics and statistical modeling identified key proteins associated with CTD, including KIF1A and PLCB1. The abundance of these proteins in the four brain regions was significantly correlated with both the object recognition and the Y-maze tests. Functional analysis confirmed their key roles and associated molecules in CTD pathogenesis