Myocardial fibrosis induced by nonylphenol and its regulatory effect on the TGF-ß1/LIMK1 signaling pathway.

OBJECTIVE: We here explored whether perinatal nonylphenol (NP) exposure causes myocardial fibrosis (MF) during adulthood in offspring rats and determined the role of the TGF-ß1/LIMK1 signaling pathway in NP-induced fibrosis in cardiac fibroblasts (CFs). METHODS AND RESULTS: Histopathology revealed increased collagen deposition and altered fiber arrangement in the NP and isoproterenol hydrochloride (ISO) groups compared with the blank group. Systolic and diastolic functions were impaired. Western blotting and qRT-PCR demonstrated that the expression of central myofibrosis-related proteins (collagens Ι and ΙΙΙ, MMP2, MMP9, TGF-ß1, α-SMA, IL-1ß, and TGF-ß1) and genes (Collagen Ι, Collagen ΙΙΙ, TGF-ß1, and α-SMA mRNA) was upregulated in the NP and ISO groups compared with the blank group. The mRNA-seq analysis indicated differential expression of TGF-ß1 signaling pathway-associated genes and proteins. Fibrosis-related protein and gene expression increased in the CFs stimulated with the recombinant human TGF-ß1 and NP, which was consistent with the results of animal experiments. According to the immunofluorescence analysis and western blotting, NP exposure activated the TGF-ß1/LIMK1 signaling pathway whose action mechanism in NP-induced CFs was further validated using the LIMK1 inhibitor (BMS-5). The inhibitor modulated the TGF-ß1/LIMK1 signaling pathway and suppressed the NP-induced increase in fibrosis-related protein expression in the CFs. Thus, the aforementioned pathway is involved in NP-induced fibrosis. CONCLUSION: We here provide the first evidence that perinatal NP exposure causes myocardial fibrosis in growing male rat pups and reveal the molecular mechanism and functional role of the TGF-ß1/LIMK1 signaling pathway in this process.

Examining the Social Networks Types and Their Effects on Caregiving Experience of Family Caregivers for Individuals With Dementia: A Mixed-Methods Study.

Background and Objectives: Social networks are crucial to personal health, particularly among caregivers of individuals with dementia; however, different types of social networks among caregivers of those with dementia and how these differences are associated with caregiver burden and positive appraisal, remain underexamined. This study aims to depict dementia caregivers' social network types, related factors, and impact on caregiving experiences. Research Design and Methods: A questionnaire-based survey was conducted with a total of 237 family caregivers of individuals with dementia nested additional semistructured interviews conducted with 14 caregivers in Chongqing, China. A quantitative study was designed to collect data on personal and situational information, social networks, caregiver burden, and positive aspects of caregiving. Qualitative data were collected via semistructured interviews. Latent class analysis and multivariate regression analyses were applied to quantitative data, and inductive content analysis to qualitative data. Results: The 3 social network types-family-limited (n = 39, 16.46%), family-dominant (n = 99, 41.77%), and diverse network (n = 99, 41.77%)-differed in age and sex of caregivers and individuals with dementia, stage of dementia, and caregiving intensity. Caregivers in family-dominant networks had a lower caregiver burden (ß= -0.299, p = .003) and greater positive aspects of caregiving (ß= 0.228, p = .021) than those in family-limited networks. Three themes-accessibility, reciprocity, and reliance-emerged as facilitators and barriers when asking for support. Caregivers frequently cited the perception of economic, practical, and emotional support, yet reported a lack of adequate formal support from healthcare providers. Discussion and Implication: Family caregivers of individuals with dementia have different social network types that vary considerably among sociocultural contexts and perceive various types of support from social networks. Solid family networks and diverse social networks are contributors to long-term dementia care.

Estimated Costs of Drug-Related Problems Prevented by Pharmacist Prescription Reviews Among Hospitalized Internal Medicine Patients.

BACKGROUND AND OBJECTIVES: Data are lacking on the estimated costs of pharmacist prescription reviews (PPRs) for hospitalized internal medicine patients. This study investigates the estimated costs of drug-related problems (DRPs) prevented by PPRs among hospitalized internal medicine patients. METHODS: We reviewed all medication orders for patients at an academic teaching hospital in China for 2 years. DRPs were categorized using the Pharmaceutical Care Network Europe classification. The severity of the potential harm of DRPs was assessed by the Harm Associated with Medication Error Classification (HAMEC) tool. The estimated cost of PPRs was calculated. RESULTS: A total of 162426 medication orders for 4314 patients were reviewed, and 1338 DRPs were identified by pharmacists who spent 2230 hours performing PPRs. Among the 1080 DRPs that were prospectively intervened upon, 703 were resolved. The HAMEC tool showed that 47.1% of DRPs were assessed as level 2, 30.4% as level 3, 20.6% as level 1, and 0.6% carried a life-threatening risk. Pharmacist interventions contributed to the prevention of DRP errors and a reduction of $339 139.44. This resulted in a mean cost saving of $482.42 per patient at an input cost of $21 495.06 over the 2 years. The benefit-cost ratio was 15.8. CONCLUSION: PPRs are beneficial for detecting potential DRPs and creating potential cost savings among hospitalized internal medicine patients.