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Non-alcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years. Diet and exercise interventions are the first-line treatment options, with weight loss via a hypocaloric diet being the most important therapeutic target in NAFLD. However, most NAFLD patients are not able to achieve such weight loss. Therefore, the requisite is the investigation of other effective therapeutic approaches. This review summarizes research on understanding complex pathophysiology underlying dietary approaches and exercise interventions with the potential to prevent and treat NAFLD.

This study introduces a lightweight storage system for wearable devices, aiming to optimize energy efficiency in long-term and continuous monitoring applications. Utilizing Direct Memory Access and the Serial Peripheral Interface protocol, the system ensures efficient data transfer, significantly reduces energy consumption, and enhances the device autonomy. Data organization into Time Block Data (TBD) units, rather than files, significantly diminishes control overhead, facilitating the streamlined management of periodic data recordings in wearable devices. A comparative analysis revealed marked improvements in energy efficiency and write speed over existing file systems, validating the proposed system as an effective solution for boosting wearable device performance in health monitoring and various long-term data acquisition scenarios.

IL-6 family cytokines are defined by the common use of the signal-transducing receptor chain glycoprotein 130 (gp130). Increasing evidence indicates that these cytokines are essential in the regulation of metabolic homeostasis as well as in the pathophysiology of multiple gastrointestinal and liver disorders, thus making them attractive therapeutic targets. Over the past few years, therapies modulating gp130 signalling have grown exponentially in several clinical settings including obesity, cancer and inflammatory bowel disease. A newly engineered gp130 cytokine, IC7Fc, has shown promising preclinical results for the treatment of type 2 diabetes, obesity and liver steatosis. Moreover, drugs that modulate gp130 signalling have shown promise in refractory inflammatory bowel disease in clinical trials. A deeper understanding of the main roles of the IL-6 family of cytokines during homeostatic and pathological conditions, their signalling pathways, sources of production and target cells will be crucial to the development of improved treatments. Here, we review the current state of the role of these cytokines in hepatology and gastroenterology and discuss the progress achieved in translating therapeutics targeting gp130 signalling into clinical practice.In this Review, the authors describe the biology of IL-6 family cytokines relevant to metabolism, liver disease and gastrointestinal disease, and discuss the potential of IL-6 family members as therapeutic agents in these areas.

In the rapidly evolving domain of conversational agents, the integration of Large Language Models (LLMs) into Chatbot Development Platforms (CDPs) is a significant innovation. This study compares the efficacy of employing generic and fine-tuned GPT-3.5-turbo models for designing dialog flows, focusing on the intent and entity recognition crucial for dynamic conversational interactions. Two distinct approaches are introduced: a generic GPT-based system (G-GPT) leveraging the pre-trained model with complex prompts for intent and entity detection, and a fine-tuned GPT-based system (FT-GPT) employing customized models for enhanced specificity and efficiency. The evaluation encompassed the systems’ ability to accurately classify intents and recognize named entities, contrasting their adaptability, operational efficiency, and customization capabilities. The results revealed that, while the G-GPT system offers ease of deployment and versatility across various contexts, the FT-GPT system demonstrates superior precision, efficiency, and customization, although it requires initial training and dataset preparation. This research highlights the versatility of LLMs in enriching conversational features for talking assistants, from social robots to interactive chatbots. By tailoring these advanced models, the fluidity and responsiveness of conversational agents can be enhanced, making them more adaptable and effective in a variety of settings, from customer service to interactive learning environments.

Cognitive deficits are very difficult to diagnose during the initial stages; tests typically consist of a patient performing punctual dual-task activities, which are subjectively analyzed to determine the cognitive decline impact on gait. This work supports novel and objective diagnosis methods by stating a baseline on how neurotypical aging affects dual tasks while using a smartphone on the move. With this aim, we propose a twofold research question: Which mobile device tasks performed on the move (dual tasking) have characteristic changes in gait parameters, and which are especially characteristic at older ages? An experiment was conducted with 30 healthy participants where they performed 15 activities (1 single task, 2 traditional dual-tasks and 12 mobile-based dual-tasks) while walking about 50 m. Participants wore a wireless motion tracker (15 sensors) that made the concise analysis of gait possible. The results obtained characterized the gait parameters affected by mobile-based dual-tasking and the impact of normal cognitive decline due to aging. The statistical analysis shows that using smartphone-based dual-tasking produces more significant results than traditional dual-tasking. In the study, 3 out of 10 gait parameters were very significantly affected (p < 0.001) when using the traditional dual tasks, while 5 out of 10 parameters were very significantly affected (p < 0.001) in mobile-based dual-tasking. Moreover, the most characteristic tasks and gait parameters were identified through the obtained results. Future work will focus on applying this knowledge to improve the early diagnosis of MCI.

Pathogenic variants of the J-domain protein DNAJC12 cause parkinsonism, which is associated with a defective interaction of DNAJC12 with tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis. In this work, we characterize the formation of the TH:DNAJC12 complex, showing that DNAJC12 binding stabilizes both TH and the variant TH-p.R202H, associated with TH deficiency. This binding delays their time-dependent aggregation in an Hsp70-independent manner, while preserving TH activity and feedback regulatory inhibition by dopamine. DNAJC12 alone barely activates Hsc70 but synergistically stimulates Hsc70 ATPase activity when complexed with TH. Cryo-electron microscopy supported by crosslinking-mass spectroscopy reveals two DNAJC12 monomers bound per TH tetramer, each embracing one of the two regulatory domain dimers, leaving the active sites available for substrate, cofactor and inhibitory dopamine interaction. Our results also reveal the key role of the C-terminal region of DNAJC12 in TH binding, explaining the pathogenic mechanism of the DNAJC12 disease variant p.W175Ter. DNAJC12 variants cause parkinsonism. Here, the authors show that DNAJC12 stabilizes tyrosine hydroxylase, a crucial enzyme in dopamine synthesis, and identify key structural motifs for this interaction, explaining the pathogenesis of truncated variants.

Background In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide.