Development and evaluation of a virtual reality driving test for patients with cirrhosis.

BACKGROUND: Patients with cirrhosis and especially those with HE may have impaired driving skills and may be prone to car accidents. This proof-of-concept study aimed to develop and evaluate the applicability of a virtual reality (VR)-based driving test in patients with cirrhosis. Additionally, the association between the results in the VR test and car accidents was investigated. METHODS: A short driving test using a VR head-mounted display (HTC Vive Pro Eye) was developed to simulate five hazardous situations. The patient has to pull the brake when the hazardous situations occur. The time from triggering the event to pressing the brake is recorded as reaction time. Total reaction time (TRT) is defined as the combined reaction time to all 5 events. Car accidents were assessed retrospectively (previous 12 months) and patients were followed prospectively for 6 months. Minimal HE (MHE) was diagnosed using Psychometric Hepatic Encephalopathy Score. RESULTS: In total, 112 outpatients with cirrhosis and 52 controls without cirrhosis were recruited. MHE was detected in 14% (n = 15). Patients with cirrhosis and MHE (5.67 s) had higher TRTs compared to patients without MHE (5.02 s) and controls without cirrhosis above the age of 50 (4.98 s) (MHE vs. no MHE or controls p<0.01, no MHE vs. controls: not significant). Seven patients reported car accidents during the twelve months prior to study inclusion. TRTs were numerically higher in patients with reported car accidents (p = 0.099). When patients who stopped driving for HE-related/cirrhosis-related reasons (n = 14) were added to the group of patients with accidents, then a longer TRT was significantly associated with the modeled outcome in univariable (p<0.01) and multivariable analyses (OR 2.83, p<0.01). Two car accidents occurred during follow-up. Both patients had TRTs above the 90th percentile. CONCLUSIONS: The VR driving test is easy and rapid to perform in patients with cirrhosis and could be helpful as a point-of-care tool for predicting car accidents.

Immunomodulatory Effects of SGLT2 Inhibitors-Targeting Inflammation and Oxidative Stress in Aging.

Given that the increase in the aging population has grown into one of the largest public health issues, inflammation and oxidative stress, which are closely associated with the aging process, became a focus of recent research. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a group of drugs initially developed as oral antidiabetics, have shown many beneficial effects over time, including improvement in renal function and cardioprotective effects. It has been shown that SGLT2 inhibitors, as a drug class, have an immunomodulatory and antioxidative effect, affecting endothelial function as well as metabolic parameters. Therefore, it is not surprising that various studies have investigated the potential mechanisms of action of SGLT2 inhibitors in age-related diseases. The proposed mechanisms by which SGLT2 inhibitors can achieve their anti-inflammatory effects include influence on AMPK/SIRT1/PGC-1α signaling, various cytokines, and the NLRP3 inflammasome. The antioxidative effect is related to their action on mitochondria and their influence on the signaling pathways of transforming growth factor ß and nuclear erythroid 2-related factor 2/antioxidant response element. Also, SGLT2 inhibitors achieve their anti-inflammatory and antioxidative effects by affecting metabolic parameters, such as uric acid reduction, stimulation of ketogenesis, reduction of body weight, lipolysis, and epicardial fat tissue. Finally, SGLT2 inhibitors display anti-atherosclerotic effects that modulate inflammatory reactions, potentially resulting in improvement in endothelial function. This narrative review offers a complete and comprehensive overview of the possible pathophysiologic mechanisms of the SGLT2 inhibitors involved in the aging process and development of age-related disease. However, in order to use SGLT2 inhibitor drugs as an anti-aging therapy, further basic and clinical research is needed to elucidate the potential effects and complex mechanisms they have on inflammation processes.

The Relationship between Nrf2 and HO-1 with the Severity of COVID-19 Disease.

Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) have significant roles in the development of a hyperinflammatory state in infectious diseases. We aimed to investigate the association of the serum concentrations of Nrf2 and HO-1 with the severity of COVID-19 disease. The study included 40 subjects with mild and moderately severe forms of the disease (MEWS scoring system ≤2). Twenty of the subjects had MEWS scores of 3 or 4, which indicate a severe form of the disease, and twenty subjects had a MEWS score of ≥5, which indicates a critical form of the disease. HO-1 and Nrf2 were measured using the commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Subjects with the most severe form of COVID-19 (critically ill) had a lower concentration of Nrf2 that negatively correlated with the markers of hyperinflammatory response (CRP, IL-6, ferritin). This observation was not made for HO-1, and the correlation between Nrf2 and HO-1 values was not established. In the mild/moderate form of COVID-19 disease, Nrf2 was associated with an increased 1,25 dihydroxy vitamin D concentration. The results of this study show that Nrf2 has a role in the body's anti-inflammatory response to COVID-19 disease, which makes it a potential therapeutic target.

When does a wedding mark the beginning of a new chapter in one's life?

Life story chapters may be formed in relation to substantial and enduring changes in material circumstances, and we explored this idea by capitalizing on naturally occurring variations in the change of material circumstances associated with marriage. In two studies, we asked participants to report whether they cohabitated before marriage and whether they relocated in connection with marriage, using these as proxies for material change. Participants described their wedding and rated it on memory characteristics along with scales measuring material change, psychological change, and centrality to identity. Next, they identified chapters within the romantic domain of their lives. Finally, they placed the wedding memory in a chapter and marked the temporal location of the memory on a timeline representing the chapter. In study 2, not cohabitating before marriage was associated with greater likelihood of locating the wedding memory as a starting point for a chapter. The results provide some support for the role of material change in shaping the formation of chapters.

Assessment of FreeStyle Libre Flash Glucose Monitoring System Implementation in Real Life Clinical Setting: A Prospective Observational Study.

BACKGROUND: In this study, we investigated the effectiveness of FreeStyle Libre Flash Glucose Monitoring (FGM) implementation in a real life clinical setting with the emphasis on the effect of initial education on the use of the FGM system. METHODS: This prospective observational study included 425 diabetes type 1 subjects followed up for 3 to 12 months (320 were followed up to 3 months, 267 up to 6 months and 147 up to period of one year). An FGM sensor was placed at study entry and all participants were educated through a period of 5 days on sensor usage and self-management of glycemia with follow up visits every 3 months. RESULTS: HbA1c values significantly decreased from baseline (T0) to 3 months (T3) (p < 0.001), with a drop from 7.48% ± 0.1% to 7.30 ± 0.1%. There was no change in time spent in hypoglycemia from T3 to T12, although there was a decreasing trend present. The change in HbA1c values in the entire cohort was driven by change in the subgroup of patients with HbA1c ≥7% with a drop from 8.22% ± 1.14% to 7.68% ± 1.26% (p < 0.0001) in the first 3 months. Also, in individuals performing SMBG less than 5 times per day, there was a steady decrease in HbA1c levels up to 6 months (p < 0.05 and p < 0.001, respectively) as opposed to those who performed SMBG ≥5 times per day. CONCLUSIONS: The improvement in HbA1c was mainly driven by the increase in the number of scans per day. The subjects with poorer glycemic control and those who seldom performed SMBG benefited the most.

What happened in kindergarten? Mother-child conversations about life story chapters.

Research indicates that adults form life story chapters, representations of extended time periods that include people, places and activities. Life chapter memories are distinct from episodic memories and have implications for behaviour, self and mental health, yet little is known about their development during childhood. Two exploratory studies examined parent-child conversations about life chapters. In Study 1, mothers recorded naturalistic conversations with their 5-6 year old children about two chapters in the child's life. In Study 2, mothers recorded conversations with their 6-7 year old children about a particular life chapter-the child's kindergarten year-and also about a specific episode of their choice. The results indicated that young children are able to recall and discuss information about life chapters and that parents actively scaffold children's discussion of general information in chapters as well as specific events. Mothers' conversational style when discussing chapters (e.g., elaborativeness) predicted children's memory contributions, and was also positively correlated with their style when discussing specific events. The results suggest new avenues for research on the ontogeny of life chapters, the factors that shape them, and their role in development.

Writing about life story chapters increases self-esteem: Three experimental studies.

OBJECTIVE: The purpose of the present three studies was to examine experimentally whether writing about life story chapters would increase self-esteem, self-concept clarity, and meaning. METHOD: In study 1, 179 participants rated state self-esteem and self-concept clarity before and after they described either four important life story chapters or four famous Americans. In study 2, 141 new participants completed a similar procedure to study 1 and then returned two days later to complete the procedure a second time. In study 3, 101 community dwelling adults completed a similar procedure to study 1, but responded to full scales measuring self-concept clarity, self-esteem, and mood. RESULTS: In all the studies, writing about four important life story chapters increased the ratings of self-esteem, whereas writing about four famous Americans did not. CONCLUSION: The studies show that writing about chapters in life stories can increase self-esteem and suggest that constructing positive self-worth may be an important function of life stories.

Vicarious memories.

People not only have vivid memories of their own personal experiences, but also vicarious memories of events that happened to other people. To compare the phenomenological and functional qualities of personal and vicarious memories, college students described a specific past event that they had recounted to a parent or friend, and also an event that a friend or parent had recounted to them. Although ratings of memory vividness, emotional intensity, visualization, and physical reactions were higher for personal than for vicarious memories, the overall pattern of ratings was similar. Participants' ratings also indicated that vicarious memories serve many of the same life functions as personal memories, although at lower levels of intensity. The findings suggest that current conceptions of autobiographical memory, which focus on past events that happened directly to the self, should be expanded to include detailed mental representations of specific past events that happened to other people.

The reminiscence bump in older adults' life story transitions.

Older adults' memories of events that occurred in adolescence and early adulthood are over-represented compared to other lifetime periods. Prior research on this reminiscence bump has focused on qualities of individual memories. The present study used a novel interview method to examine the potential role played by mental representations of extended lifetime periods. Older adults provided oral life stories, and they divided their transcribed narratives into "chapters". Participants' ages at chapter beginnings and endings showed pronounced reminiscence bumps. The results are consistent with the idea that personal episodes occurring near the boundaries of extended lifetime periods receive preferential processing that enhances long-term memory.