Using Augmented Reality with Older Adults in the Community to Select Design Features for an Age-Friendly Park: A Pilot Study.

Sedentary behavior is prevalent in older adults. Older adults often underutilize public parks for exercising because the parks do not support their needs and preferences. Engaging older adults on the redesign of parks may help promote active lifestyles. The objectives of this pilot study were to evaluate (1) the effects of wearing augmented reality (AR) and virtual reality (VR) glasses on balance; (2) the effects of different virtual walls separating the walking trail from the roadway on older adults' gait, and (3) the preferences of the participants regarding wall design and other features. The participants were ten older adults (68 ± 5 years) who lived within two miles from the park. Balance and gait were assessed using a force plate and an instrumented mat. It was feasible to use AR with older adults in the park to evaluate features for redesign. Motion sickness was not an issue when using AR glasses, but balance was affected when wearing VR goggles. The area of postural sway increased approximately 25% when wearing AR glasses, and it increased by close to 70% when wearing VR goggles compared to no glasses. This difference is clinically relevant; however, we did not have enough power to identify the differences as statistically significant because of the small sample size and large variability. Different walls did not significantly affect the participants' gait either because they did not alter the way they walked or because the holograms were insufficiently realistic to cause changes. The participants preferred a transparent wall rather than tall or short solid walls to separate the park from the roadway.

The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases.

Ubiquitination is a multi-step enzymatic process that involves the marking of a substrate protein by bonding a ubiquitin and protein for proteolytic degradation mainly via the ubiquitin-proteasome system (UPS). The process is regulated by three main types of enzymes, namely ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Under physiological conditions, ubiquitination is highly reversible reaction, and deubiquitinases or deubiquitinating enzymes (DUBs) can reverse the effect of E3 ligases by the removal of ubiquitin from substrate proteins, thus maintaining the protein quality control and homeostasis in the cell. The dysfunction or dysregulation of these multi-step reactions is closely related to pathogenic conditions; therefore, understanding the role of ubiquitination in diseases is highly valuable for therapeutic approaches. In this review, we first provide an overview of the molecular mechanism of ubiquitination and UPS; then, we attempt to summarize the most common diseases affecting the dysfunction or dysregulation of these mechanisms.

Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression.

Protein kinase C (PKC) isozymes are members of the Serine/Threonine kinase family regulating cellular events following activation of membrane bound phospholipids. The breakdown of the downstream signaling pathways of PKC relates to several disease pathogeneses particularly neurodegeneration. PKC isozymes play a critical role in cell death and survival mechanisms, as well as autophagy. Numerous studies have reported that neurodegenerative disease formation is caused by failure of the autophagy mechanism. This review outlines PKC signaling in autophagy and neurodegenerative disease development and introduces some polyphenols as effectors of PKC isozymes for disease therapy.

Service-Learning through conference-based, interdisciplinary workshops on Age-Friendly design.

For three consecutive years, the Age-Friendly Design Committee (AFDC) of the Academy for Gerontology in Higher Education (AGHE) used AGHE's annual meeting as a platform to conduct community-based service-learning workshops focusing on age-friendly design. These workshops assembled local stakeholders, conference attendees from multiple disciplines, and landscape and architectural designers to discuss age-friendly design issues and solutions for local environments. Each workshop provided hands-on design experience and the opportunity for AGHE participants to contribute to conference host communities by using their gerontological expertise to translate knowledge into practice. Local stakeholders learned the value of gerontological input when considering design issues. We describe the process of incorporating service-learning into the conference experience through age-friendly design workshops and how these bring together students, faculty, and design professionals from different backgrounds and disciplines to address local age-friendly design issues.

Impairment of lipophagy by PNPLA1 mutations causes lipid droplet accumulation in primary fibroblasts of Autosomal Recessive Congenital Ichthyosis patients.

BACKGROUND: Autosomal Recessive Congenital Ichthyosis (ARCI) is a group of epidermal keratinization disorders. One of the disease-associated proteins, patatin-like phospholipase domain-containing protein-1 (PNPLA1), plays a key role in the epidermal omega-O-acylceramide synthesis and localizes on the surface of lipid droplets (LDs). OBJECTIVE: Previously, routine clinical test results showed abnormal LD accumulation in blood smear samples of our ARCI patients with PNPLA1 mutations. To investigate the abnormal accumulation of LDs, we analyzed primary fibroblast cells of ARCI patients with PNPLA1 mutations (p.Y245del and p.D172N). We hypothesized that PNPLA1 mutations might affect lipophagy-mediated regulation of LDs and cause intracellular lipid accumulation in ARCI patients. METHODS: LD accumulation was analyzed by fluorescence staining with BODIPY®493/503 in the fibroblasts of patient cells and PNPLA1 siRNA transfected control fibroblast cells. The expression of PNPLA1 and its effects on the lipophagy-mediated degradation of LDs were analyzed by immunocytochemistry and immunoblotting. RESULTS: Our results showed that mutant or downregulated PNPLA1 protein causes abnormal intracellular LD accumulation. We found that PNPLA1 mutations affect neither the cellular localization nor the expression levels of the protein in fibroblast cells. When we analyzed lipophagic degradation process, LC3 expression and the number of autophagosomes were significantly decreased in fibroblast cells of the patients. In addition, co-localization of LDs with autophagosomes and lysosomes were markedly less than that of the control group. CONCLUSION: PNPLA1 mutations caused disturbances in both autophagosome formation and fusion of autophagosomes with lysosomes. Our results indicate a possible role for PNPLA1 protein in LD regulation via lipophagy-mediated degradation.

Association between selected cholesterol-related gene polymorphisms and Alzheimer's disease in a Turkish cohort.

Numerous genetic evidence has pointed out that variations in cholesterol-related genes may be associated with an Alzheimer's disease (AD) risk. We aimed to investigate the association between polymorphisms in several cholesterol-related genes [APOA5 (rs662799), APOC1 (rs11568822), APOD (rs1568565), CH25H (rs13500), LDLR (rs5930), SORL1 (rs2282649)] and AD in a cohort of Turkish patients. The study group consisted of 257 AD patients (mean age: 75.9 years ± 10.4) and 414 controls (mean age: 62.2 years ± 13.1). Genotyping was performed by quantitative real-time polymerase chain reaction using hydrolysis probes. Our results showed that the 'TT' genotype of CH25H rs13500 polymorphism was significantly more frequent in the AD group (p < 0.001) and individuals carrying the CH25H 'T' allele had an increased risk for AD (OR 3.07, 95% CI 2.13-4.44, p = 2.20e-09) independently from age, gender and APOE ε4 allele. Moreover, this risk was excessively increased (OR 14.04, 95% CI 6.99-28.23, p = 9.78e-14) in the presence of APOE ε4 allele. The 'ins/ins' genotype of APOC1 rs11568822 was significantly more frequent in the AD group compared to controls (p = 1.95e-08). However, this increased AD risk in 'ins/ins' carriers was found to be dependent on their APOE ε4 carrier status. No significant associations were found in allele and genotype distributions of APOA5, APOD, LDLR and SORL1 gene polymorphisms. Our results suggest that the association between APOC1 'ins/ins' genotype and AD risk can be explained by linkage disequilibrium with the APOE locus. CH25H rs13500 polymorphism is associated with an AD risk in the Turkish population and CH25H might have a role in the pathogenesis of AD together with, and independently from APOE.

Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related Hepatocellular Carcinoma.

The proportion of obese or diabetic population has been anticipated to increase in the upcoming decades, which rises the prevalence of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). Recent evidence indicates that NASH is the main cause of chronic liver diseases and it is an important risk factor for development of hepatocellular carcinoma (HCC). Although the literature addressing NASH-HCC is growing rapidly, limited data is available about the etiology of NASH-related HCC. Experimental studies on the molecular mechanism of HCC development in NASH reveal that the carcinogenesis is relevant to complex changes in signaling pathways that mediate cell proliferation and energy metabolism. Genetic or epigenetic modifications and alterations in metabolic, immunologic, and endocrine pathways have been shown to be closely related to inflammation, liver injury, and fibrosis in NASH along with its subsequent progression to HCC. In this review, we provide an overview on the current knowledge of NASH-related HCC development and emphasize molecular signaling pathways regarding their mechanism of action in NASH-derived HCC.