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Aims Mechanosensitive (MS) ion channels play a key role in heart development, physiology, and disease. However, little is known about the molecular mechanisms of the MS non-selective cationic channel Piezo family in cardiac fibrosis. Methods and results Mice were treated with ISO/Ang-II/TAC to induce cardiac fibrosis. AAV9 carrying POSTN promoter-driven small hairpin RNA targeting YTHDF1 , and Piezo2 were administered to ISO mice to investigate their roles in cardiac fibrosis. RNA-seq, single-cell sequencing, and histological and biochemical analyses were performed to determine the mechanism by which YTHDF1 regulates Piezo2 expression in cardiac fibrosis. Piezo2 was reconstituted in YTHDF1 -deficient cardiac fibroblasts (CFs) and mouse hearts to study its effects on CF autophagy and fibrosis. Piezo2 but not Piezo1 expression increased in experimental cardiac fibrosis and TGF-β1-induced CFs. Fibroblast-specific Piezo2 deficiency ameliorated fibroblast activation and autophagy and inhibited cardiac fibrosis. Mechanistically, Piezo2 up-regulation was associated with elevated m6A mRNA levels. Site-specific m6A modifications at peak_26355 were crucial for regulating the binding of YTHDF1 to Piezo2 mRNA and inducing Piezo2 translation. Notably, Piezo2 epitranscriptomic repression ameliorated experimental cardiac fibrosis. Conclusions We demonstrated a novel epitranscriptomic mechanism through which YTHDF1 recognizes Piezo2 and controls cardiac fibroblast autophagy and fibrosis through m6A-dependent modulation. Our findings provide new insights for the development of preventive measures for cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Background: N6-methyladenosine (m6A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m6A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive. Methods: Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1flox/flox) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase separation inhibitor 1,6-hexanediol were administered to investigate their roles in diabetic cardiac fibrosis. Histological and biochemical analyses were performed to determine how Alkbh5 and Ythdf2 regulate Notch1 expression in diabetic cardiac fibrosis. NOTCH1 was reconstituted in ALKBH5- and YTHDF2-deficient cardiac fibroblasts and mouse hearts to study its effects on mitochondrial fission and diabetic cardiac fibrosis. Heart tissue samples from patients with diabetic cardiomyopathy were used to validate our findings. Results: In mice with diabetic cardiac fibrosis, decreased Notch1 expression was accompanied by high m6A mRNA levels and mitochondrial fission. Fibroblast-specific deletion of Notch1 enhanced mitochondrial fission and cardiac fibroblast proliferation and induced diabetic cardiac fibrosis in mice. Notch1 downregulation was associated with Alkbh5-mediated m6A demethylation in the 3'UTR of Notch1 mRNA and elevated m6A mRNA levels. These elevated m6A levels in Notch1 mRNA markedly enhanced YTHDF2 phase separation, increased the recognition of m6A residues in Notch1 mRNA by YTHDF2, and induced Notch1 degradation. Conversely, epitranscriptomic downregulation rescues Notch1 expression, resulting in the opposite effects. Human heart tissues from patients with diabetic cardiomyopathy were used to validate the findings in mice with diabetic cardiac fibrosis. Conclusions: We identified a novel epitranscriptomic mechanism by which m6A-mediated phase separation suppresses Notch1 expression, thereby promoting mitochondrial fission in diabetic cardiac fibrosis. Our findings provide new insights for the development of novel treatment approaches for patients with diabetic cardiac fibrosis. [ABSTRACT FROM AUTHOR]

The self-weight of a reinforced concrete beam contributes to the permanent loads of a structure. This can be reduced by creating a longitudinal void along the beam so that it will not affect the performance of the beam. In addition, this process can reduce the amount of building cost. Therefore, a finite element model was developed in this study with the aid of a computer program, Ansys, to investigate the behavior of the hollow beam. The model was tested for reliability by comparing the predicted results with those obtained from the experiment in terms of the load-displacement responses, mechanical properties, and parametric responses. The result showed that the reliability of the model was questionable. The main cause of the non-reliability was the inaccurate prediction of the beam deflection by the model. The poor prediction of beam deflection led to significant variations of relevant mechanical properties including stiffness, deflection, and ductility. For beam deflection, only 1/3 of the specimens were correctly predicted with a reliability of 36% while the strength properties were discovered to have higher values as observed in the yield and the ultimate strengths with 73% and 64% respectively. However, both the model and experimental results showed the hollow beam was relatively effective when the diameter of the longitudinal void was 1/3 times the beam width and placed at the neutral axis. For the evaluation to improve the reliability, some revision including the properties of the materials, boundary conditions of the beam support, bonding conditions between different materials, and meshing shape and size suppose to be applied to the model.

A structured interview survey was conducted in a major city in Taiwan to explore and compare older and younger family primary caregivers' well being and their future caregiving plans for these adults with intellectual disability. The sample size was 315 caregivers who were 55 years or older and who cared for adults with intellectual disability and 472 similar caregivers who were under 55 years of age. The results indicated that the older caregivers compared with younger ones reported a lower quality of life, less family support, a more negative perception of having a family member with intellectual disability, and greater worries about the future care arrangements of the adult with intellectual disability. Statistical analysis showed that predisposing, enabling, and need factors influenced the caregivers' future caregiving options.

Background: No studies have ever been conducted concerning menstrual experiences among women with an intellectual disability in Taiwan. Materials and Methods: An in-depth interview was conducted at three public institutions and perceptions and experiences regarding menstruation were elicited from 55 women aged 21-65 years. Results: The participants knew about menstrual blood and could recognize the experiences of period pain and its link to femininity. The women's management of menstruation played a big part in their institutionalized life, where they had relatively limited choice and autonomy. Positive feelings towards the menstrual cycle were experienced by some participants; however, many had negative attitudes towards sexual activities or parenting, even though they knew the association between menstruation and pregnancy. Conclusions: Although these women's experiences of perimenstrual symptoms are quite similar to those of women without intellectual disability, their menstrual management, interpretations and attitudes to menses are influenced by their institutional life and by the society at large.

Background: The disability policy in Taiwan has traditionally emphasized residential care in large institutions and, more recently, medium-sized group homes. This paper compares the relative costs, services provided and outcomes between the traditional institutions, medium-sized group homes and new small-scale community living units that were launched in 2004 in Taiwan. Materials and Methods: Cross-sectional analysis was used to investigate the three current residential service models. A total of 248 participants with intellectual disabilities were interviewed, including all residents from the existing 25 small residential units and purposively sampled respondents from the other two residential models. Results: Outcomes for the Taiwanese participants were consistent with the existing literature on deinstitutionalization from Western societies. Small homes provided better subjective and objective quality of life than both medium-sized community-based units and traditional institutions. Conclusion: Participants living in small residential homes experienced better outcomes at lower cost than persons living in medium-sized group homes or institutions.

Background: Taiwanese family carers of people with intellectual disabilities not only suffer from long-term stress but also need to cope with social difficulties. The aim of this study is to evaluate the quality of life (QOL) among family carers of people with intellectual disabilities. Materials and methods: A census interview survey was conducted in Hsin-Chu City in Taiwan and included the primary family caregivers of 792 adults with intellectual disability who were living with their families. The survey packet contained the WHOQOL-BREF Taiwan-version scale with four core domains and the activities of daily life/instrumental activities of daily life (ADL/IADL) scales. Results: The mean score for "physical" was highest and that for "environment" was lowest. The strongest predictors of caregivers QOL were the caregiver's health status, their family income and the level of severity of the intellectual disability of the adult. Conclusions: The results of the study support the need to expand services and individualize support to families of adults with intellectual disability living in family homes.

Background: Approximately 50% of residents living in institutions have insufficient fluid intake, and 20%–30% experience dehydration. Implementing strategies that effectively increase fluid intake is crucial to preventing dehydration-related complications and reducing complications and comorbidities in this population. Purpose: This study was designed to explore the effects on fluid intake and hydration status of a hydration game-based learning program in institutional residents. Methods: A single-blind, cluster, randomized controlled trial was conducted. Sixty-four subjects from five long-term care facilities in northern Taiwan were randomly assigned to either an experimental or control group. The experimental group received a 40-minute game-based hydration care program intervention twice weekly for 8 weeks. The control group received routine care. The data obtained were analyzed using generalized estimating equation analysis to verify changes in observed variables in the two groups at 4 and 8 weeks (during and immediately after the intervention). Results: The results showed a significant improvement in fluid intake in the experimental group at 4 and 8 weeks (p =.002 and p <.001, respectively). In terms of dehydration-related indicators, although total body water was significantly improved at 8 weeks in the experimental group (p =.009), no significant improvement was found in urine-specific gravity. In terms of signs of possible urinary tract infection, the experimental group showed significant improvement in urine leukocytes (p =.029) and nitrites (p =.004) at 8 weeks. Conclusions/Implications for Practice: The findings of this study support the positive effects of applying the concept of uncertain rewards and game-based learning in institutional group activities. Specifically, the interventions increased social interaction and enhanced enjoyment of drinking. The findings call for nursing professionals at institutions to offer similar hydration game-based learning programs as part of residents' daily activities to improve fluid intake. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of a symptom management program on self-care of medication side effects among AIDS/HIV-positive patients. Sixty-seven patients from a sexually transmitted disease control center, a medical center, and a Catholic AIDS support group in Taipei were randomly assigned to three groups: one-on-one teaching, group teaching, and a control group. All subjects in each teaching group attended a 60- or 90-minute program on highly active antiretroviral therapy (HAART) side effect self-care education and skill training once per week for 3 weeks; subjects also underwent counseling by telephone. A medication side effect self-care knowledge questionnaire, Rosenberg's Self-Esteem Scale (RSES), and unscheduled hospital visits were used to evaluate the effectiveness of the symptom management program. The results revealed there were significant differences in mean difference of knowledge and unscheduled hospital visits between baseline and posttesting at 3 months for symptom management in the two groups. The mean difference of the self-esteem scale was not significant between the two groups. In summary, the symptom management program effectively increased the ability of AIDS/HIV-positive patients to self-care for medication side effects. We recommend that this program be applied in the clinical nursing practice.