Search

Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication. It is known that microtubules are destabilized by tau-hyperphosphorylation, which causes tau proteins to detach from microtubules and form neurofibril tangles. However, how tau-phosphorylation affects the transport dynamics of motor proteins on the microtubule remains unknown. Here, we discover that the long-distance unidirectional motion of vesicle-motor protein multiplexes (VMPMs) in living cells is suppressed under tau-hyperphosphorylation, with the consequent loss of fast vesicle-transport along the microtubule. The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion, with dynamic properties far different from those of VMPM motion in normal cells. We establish a parsimonious physicochemical model of VMPM’s active motion that provides a unified, quantitative explanation and predictions for our experimental results. Our analysis reveals that, under hyperphosphorylation conditions, motor protein multiplexes have both static and dynamic motility fluctuations. The loss of fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.

Background: YouTube is a widely used video sharing and social networking platform among children and adolescents. However, research on YouTube usage among this population remains scarce. Specifically, studies on factors that influence children and adolescents' usage are clinically significant but largely lacking. Additionally, few studies have examined the association between usage and emotional/behavioral problems, which is fundamental to smartphone research. Therefore, this study explored the relationship between early childhood temperament, subsequent YouTube usage patterns, and emotional/behavioral problems. Methods: The Kids Cohort for Understanding Internet Addiction Risk Factors in Early Childhood (K-CURE) is the first long-term prospective cohort study in Korea aimed at understanding the long-term effects of media exposure on young children. The study included 195 children aged 8–11 years enrolled in the K-CURE study. Caregivers, predominantly mothers, who voluntarily participated during their visits to community centers for children's mental health in Korea's major cities, completed a detailed self-administered survey. Childhood temperament was measured in 2018 when the children were 5–8 years old. Subsequent YouTube usage patterns and emotional/behavioral problems were assessed in 2021. Data were analyzed using frequency analysis, correlation analysis, and multiple linear regression. Results: The study found that 21.0% of children started using YouTube before age 4, with the most common onset age being 8–9 years (30.3%). These children used YouTube on average 4.8 days per week for 68.5 min per day. Early childhood persistence was negatively associated with the subsequent YouTube usage duration, and the age at first YouTube use was negatively correlated with subsequent usage frequency. Furthermore, a younger age at first YouTube use and higher usage frequency were significantly associated with increased emotional/behavioral problems. Conclusions: In the YouTube environment, where content is automatically recommended based on user preferences, traits related to usage patterns may be associated with persistence, which is linked to self-regulation. Considering the current trend where children use smartphones, contents frequently for very short durations, our findings highlight the importance of self-regulation in the media usage of children who are still developing. Additionally, our results provide fundamental information for future YouTube studies and illustrate similarities and differences between smartphone and YouTube research. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and 10%–20% occurs in lean individuals. There is little data in the literature regarding outcomes in an ethnically‐diverse patient populations with MASLD. Thus, we aim to investigate the natural history and ethnic disparities of MASLD patients in a diverse population, and stratified by body mass index categories. Methods: We conducted a retrospective multicenter study on patients with MASLD at the Banner Health System from 2012 to 2022. Main outcomes included mortality and incidence of cirrhosis, cardiovascular disease, diabetes mellitus (DM), liver‐related events (LREs), and cancer. We used competing risk and Cox proportional hazard regression analysis for outcome modelling. Results: A total of 51 452 (cross‐sectional cohort) and 37 027 (longitudinal cohort) patients were identified with 9.6% lean. The cohort was 63.33% European ancestry, 27.96% Hispanic ancestry, 3.45% African ancestry, and 2.31% Native American/Alaskan ancestry. Median follow‐up was 45.8 months. After adjusting for confounders, compared to European individuals, Hispanic and Native American/Alaskan patients had higher prevalence of cirrhosis and DM, and individuals of Hispanic, African, and Native American/Alaskan ancestry had higher mortality and incidence of LREs and DM. Lean patients had higher mortality and incidence of LREs compared with non‐lean patients. Conclusion: Native American/Alaskan, Hispanic, and African patients had higher mortality and incidence of LREs and DM compared with European patients. Further studies to explore the underlying disparities and intervention to prevent LREs in lean patients, particularly several ethnic groups, may improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: Sex steroid hormones and sex hormone-binding globulin (SHBG) have a role in predisposing individuals to nonalcoholic fatty liver disease (NAFLD), but their effects are known to differ between men and women. The testosterone- to-estradiol ratio (T/E2 ratio) and free androgen index (FAI) were known biomarkers for the hormonal milieu. We investigated whether sex steroid hormones, T/E2 ratio, FAI, and SHBG were associated with NAFLD in US adults. Methods: A cross-sectional analysis using the 2013--2016 National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI) and the US fatty liver index (USFLI) without other causes of chronic liver disease. Results: Out of 8687 subjects (49.5% male), low total testosterone levels were associated with progressively higher odds of NAFLD in men. Increasing T/E2 ratio was inversely associated with higher odds of NAFLD in men. Low serum SHBG levels were independently associated with an increased risk of NAFLD regardless of sex and menopausal status. Increasing FAI was independently associated with NAFLD. When we additionally adjusted for SHBG, T/E2 ratio, not total testosterone, was inversely associated with NAFLD in a dose-dependent manner. Increasing FAI was associated with higher odds of NAFLD in premenopausal women and marginally associated with NAFLD in postmenopausal women. Conclusion: The T/E2 ratio and SHBG were inversely associated with an increased risk of NAFLD in men. In women, increasing FAI was associated with NAFLD, whereas SHBG was inversely associated with NAFLD. [ABSTRACT FROM AUTHOR]

Background: Depression has been associated with nonalcoholic fatty liver disease (NAFLD). Data addressing the impact of depression on NAFLD‐related mortality are evolving. We aim to study the association of depression in NAFLD and all‐cause/cause‐specific mortality in the United States. Methods: A total of 11,877 individuals with NAFLD in the 2007–2016 National Health and Nutrition Examination Survey with the availability of linked mortality through 2019 were analysed. NAFLD was defined by utilizing the hepatic steatosis index in the absence of known causes of chronic liver disease. Depression and functional impairment due to depression were assessed using the Patient Health Questionnaire. Results: During the median follow‐up of 7.6 years, individuals with depression among individuals with NAFLD had a 35% higher all‐cause mortality than those without depression (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03–1.75) after adjusting for demographic, lifestyle and clinical risk factors. NAFLD with functional impairment due to depression had a 62% higher all‐cause mortality than NAFLD without functional impairment (HR: 1.62, 95% CI: 1.10–2.39). Depression in NAFLD was associated with an approximately 50% increase in the risk for cardiovascular mortality, with a 2‐fold higher cardiovascular mortality in those with functional impairment compared to those without (HR: 2.07, 95% CI: 1.30–3.30). However, there was no significant difference in cancer‐ and accident‐related mortalities in NAFLD with or without depression. Conclusions: Depression among individuals with NAFLD was associated with a higher risk for all‐cause and cardiovascular mortality in the United States. [ABSTRACT FROM AUTHOR]

Aims and objectives: To identify the factors influencing the intent to provide care among nurses involved in coronavirus disease 2019 (COVID‐19) care. Background: COVID‐19 was first reported in Wuhan, China, in 2019. In 2020, the World Health Organisation declared it a pandemic, leading to 5,827,104 deaths and 421,203,495 confirmed cases as of 19 February 2022. The high transmissibility of COVID‐19 has prolonged the pandemic for over 2 years, resulting in deleterious effects on nurses' physical and mental health. The fear of infection and isolation may lead to negative experiences and perceptions among COVID‐19 frontline nurses, which may ultimately degrade the quality of patient care. Thus, it is essential to identify factors influencing of nurses' intent to provide care. Design: Cross‐sectional study. Methods: Data were collected from 169 nurses involved in direct COVID‐19 care at a hospital designated for infectious disease care in Korea from August to September 2021 using an online questionnaire. STROBE checklist was followed. Results: Nurses' intent to provide care significantly differed based on whether they lived with parents and had adequate availability of personal protection equipment. The correlation analysis indicated that the intent to provide care was significantly positively correlated with normative beliefs, control beliefs, attitude towards the behaviour, subjective norms and perceived behavioural control. Perceived behavioural control, control beliefs and attitude towards the behaviour were significant factors influencing nurses' intent to provide COVID‐19 care. Conclusion: This study showed that nurses perceived behavioural control and positive behaviour towards providing COVID‐19 care fundamentally influenced their intent to provide care. Relevance to clinical practice: In clinical practice, the safety and rights of individual nurses who participated in COVID‐19‐related patient care are promoted, and ultimately, the quality of patient care is improved. Furthermore, active support at the organisation and government level is needed to strengthen the capabilities necessary for nursing patients with infectious diseases. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Verma et al papers. To view these articles, visit https://doi.org/10.1111/apt.17891 and https://doi.org/10.1111/apt.17913 [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Metabolic dysfunction‐associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease worldwide. A new entity termed MetALD has also been described and is defined as individuals with MASLD and increased alcohol intake. However, the natural history of MetALD compared with MASLD is unknown. We aimed to compare longitudinal outcomes in patients with MASLD versus MetALD.This study was performed using data from the National Health and Nutrition Examination Survey from 2011 to 2018. MASLD patients (defined by the United States Fatty Liver Index > 30) who met cardiometabolic criteria including body mass index (BMI) > 25 (BMI > 23 in Asians), hypertension, diabetes mellitus, dyslipidemia, and hypertriglyceridemia were included. MetALD was defined as MASLD with increased alcohol intake (3–6 standard drinks per day in males; 2–5 standard drinks per day in females). A comparison of overall, cardiovascular, cancer‐related, and other causes of mortality in patients with MASLD versus MetALD was performed.A total of 2838 individuals with MASLD and 2557 individuals with MetALD were included with a median follow‐up time of 56 months. MetALD patients were at increased risk of cancer‐related mortality compared with patients with MASLD (hazard ratio 1.32; 95% confidence interval 1.14–1.53; P < 0.01). However, there was no significant difference in overall, cardiovascular, and other causes of mortality.Patients with MetALD were at higher risk for cancer‐related mortality than MASLD. Close attention to regular cancer surveillance and accurate classification of alcohol consumption in individuals with diagnosed MASLD is warranted to help improve patient care and outcome. [ABSTRACT FROM AUTHOR]

Background: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aβ) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition. Methods: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. Results: No associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition. Conclusion: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the multidimensional relationships among factors influencing decision-making processes regarding women's willingness to marry and childbirth in South Korea with recognizing the context of family development in East Asian cultures. To this end, we employed three different analytical approaches, including classification tree modeling, Cox proportional hazard modeling, and permutation feature importance evaluation. Leveraging longitudinal data specific to Korean women, we highlighted the significance of socio-economic factors in family development dynamics. Our findings revealed that financial stability played a crucial role. Unmarried women's willingness to marry was influenced by their perspectives on economic stability, while households' consumption capacity and financial capability determined childbirth decisions and timing. We observed a trend of postponed marriage among women in their marriageable age range, particularly those with stable economic situations, reflecting a prevalent trend of skepticism of marriage in Korean society. Additional findings related to values, cultural factors, and personal happiness also suggested the challenges that discourage younger generations from entering into marriage and starting families in South Korea. By offering insights into these dynamics, our study provides practical implications for addressing the obstacles faced, contributing to a better understanding of family development dynamics. [ABSTRACT FROM AUTHOR]

Despite the aging population, studies on the subject are scarce, notably focusing on the impotence experienced by older adults when purchasing food products. This research aims to analyze the vulnerability of older people during their food purchases. Amid the COVID-19 pandemic, we conducted 17 telephone semi-structured interviews with people aged 60 or over, food buyers in person, identified as independent. The content analysis using the software IRAMUTEQ showed problematic packaging and labels; predisposition to repeat previous choices due to the wide variety of foods; excessive portions incompatible with the social changes experienced by older adults; reduction of commensality; physical elements of the supermarket excluding older adults; and the COVID-19 pandemic as an impediment to maximizing well-being due to changes in habits and alternative shopping modalities needs. As a contribution, we propose an empirical vulnerability model that considers the particularities of older people for the food market and other markets. [ABSTRACT FROM AUTHOR]

DC transformers have emerged as essential devices for medium voltage DC (MVDC)-low voltage DC (LVDC) distribution systems. However, conventional step-down single-level converters have limits on the voltage level of the MVDC-LVDC distribution system. This paper proposes a non-isolated step-down (NISD) DC transformer based on discontinuous conduction mode (DCM). The proposed structure can withstand high voltage levels by sharing voltages between energy storage modules dividing voltage levels. The proposed NISD DC transformer determines operational modes based on energy storage modules and performs the voltage conversion process. The effectiveness of the proposed NISD DC transformer is verified based on a case study using a power system computer-aided design and electromagnetic transient simulation engine including DC (PSCAD/EMTDC™). [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is known as a chronic disease characterized by eczematous and pruritus skin lesions. The pathology behind atopic dermatitis etiology is loss of epidermal barrier, which prevents the production of protein filaggrin that can induce T-cell infiltration and inflammation. Treatment of AD is majorly based on limiting skin repair as well as reducing inflammation and itching. There are several remedies available for the treatment of AD, such as Janus kinase and calcineurin inhibitors, topical corticosteroids, and phosphodiesterase-4 inhibitors. The conventional formulations in the market have limited safety and efficacy. Hence, effective treatment of atopic dermatitis requires the development of novel, efficacious, reliable, and specific therapies. Recent research data have revealed that some naturally occurring medicinal plants have potential applications in the management of AD through different mechanisms. The nanotechnology-based therapeutics have gained a lot of attention in the last decade for the improvement in the activity of drugs having low absorption due to poor solubility, thus leading to lesser bioavailability. Therapies based on nanotechnology can be an effective way to overcome these obstacles. Due to their effective propensity to provide better drug diffusion and bioavailability as well as drug targeting potential at the desired site of action, these approaches may have decreased adverse drug effects, better penetration, and enhanced therapeutic efficacy. Hence, this review highlights the potential of phytoconstituents-based novel formulations for the treatment of atopic dermatitis. Furthermore, recent patents on therapeutic approaches to atopic dermatitis have also been briefly described., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)