ACS Publications最新文献

In β‑thalassemia, excessive α‑globin chain impedes the normal development of red blood cells resulting in anemia. Numerous miRNAs, including miR‑6747‑3p, are aberrantly expressed in β‑thalassemia major (β‑TM), but there are no reports on the mechanism of miR‑6747‑3p in regulating red blood cell lineage development and fetal hemoglobin (HbF) expression. In the present study, RT‑qPCR was utilized to confirm miR‑6747‑3p expression in patients with β‑TM and the healthy controls. Electrotransfection was employed to introduce the miR‑6747‑3p mimic and inhibitor in both HUDEP‑2 and K562 cells, and red blood cell lineage development was evaluated by CCK‑8 assay, flow cytometry, Wright‑Giemsa staining and Benzidine blue staining. B‑cell lymphoma/leukemia 11A (BCL11A) was selected as a candidate target gene of miR‑6747‑3p for further validation through FISH assay, dual luciferase assay and Western blotting. The results indicated that miR‑6747‑3p expression was notably higher in patients with β‑TM compared with healthy controls and was positively related to HbF levels. Functionally, miR‑6747‑3p overexpression resulted in the hindrance of cell proliferation, promotion of cell apoptosis, facilitation of cellular erythroid differentiation and γ‑globin expression in HUDEP‑2 and K562 cells. Mechanistically, miR‑6747‑3p could specifically bind to the 546‑552 loci of BCL11A 3'‑UTR and induce γ‑globin expression. These data indicate that upregulation of miR‑6747‑3p affects red blood cell lineage development and induces HbF expression by targeting BCL11A in β‑thalassemia, highlighting miR‑6747‑3p as a potential molecular target for β‑thalassemia therapy.

Osteosarcoma malignancy exhibits significant heterogeneity, comprising both osteosarcoma stem cells (OSCs) and non‑OSCs. OSCs demonstrate increased resistance to chemotherapy due to their distinctive cellular and molecular characteristics. Alterations in mitochondrial morphology and homeostasis may enhance chemoresistance by modulating metabolic and regulatory processes. However, the relationship between mitochondrial homeostasis and chemoresistance in OSCs remains to be elucidated. The present study employed high‑resolution microscopy to perform multi‑layered image reconstructions for a quantitative analysis of mitochondrial morphology. The results indicated that OSCs exhibited larger mitochondria in comparison with non‑OSCs. Furthermore, treatment of OSCs with cisplatin (CIS) or doxorubicin (DOX) resulted in preserved mitochondrial morphological stability, which was not observed in non‑OSCs. This finding suggested a potential association between mitochondrial homeostasis and chemoresistance. Further analysis indicated that dynamin‑related protein 1 (DRP1) might play a pivotal role in maintaining the stability of mitochondrial homeostasis in OSCs. Depletion of DRP1 resulted in the disruption of mitochondrial stability when OSCs were treated with CIS or DOX. Additionally, knocking out DRP1 in OSCs led to a reduction in chemoresistance. These findings unveil a novel mechanism underlying chemoresistance in osteosarcoma and suggest that targeting DRP1 could be a promising therapeutic strategy to overcome chemoresistance in OSCs. This provided valuable insights for enhancing treatment outcomes among patients with osteosarcoma.

Objectives: To explore anxiety experienced by caregivers providing home-based, end-of-life care to patients with cancer. We examined the relationship between caregiver anxiety and receipt of palliative care by the patient. Methods: A case series of terminal cancer patient-caregiver dyads (n = 223) were recruited from oncology clinics in Virginia and Pennsylvania and followed for 12 months or until patient death. Data collected included qualitative, quantitative, and observational data; this analysis utilizes the quantitative data. Longitudinal Latent Growth Models were used to characterize the heterogeneity of primary caregiver anxiety over time. The influence of palliative care on caregiver anxiety over time was assessed. Characteristics associated with membership in the trajectory groups rendered from those models are presented. Results: The majority of caregivers were female (73.9%), white (54.9%), and patient spouses (45.3%). Three classes of caregivers were identified based on their anxiety scores over time (low, elevated, and high). The 2 groups who had elevated and high anxiety had significant increases in anxiety over time. Controlling for patient receipt of palliative care attenuated those increases. Caregivers with the lowest level of anxiety were more likely to be Black, report fewer symptoms of depression or caregiver burden and higher self-rated physical health. Caregivers who were younger reported higher anxiety. Conclusions: Our analysis detected 3 distinct cancer caregiver groups reporting low, elevated, and very high levels of anxiety. Caregivers with elevated or high anxiety also demonstrated increasing anxiety overtime; however increases were attenuated with patient receipt of palliative care. For cancer caregivers with elevated and high levels of anxiety, palliative care buffers further deterioration of their mental health.

Glioma, a type of brain tumor, is influenced by mechanical forces in its microenvironment that affect cancer progression. However, our understanding of the contribution of compression and its associated mechanisms remains limited. The objective of the present study was to create an environment in which human brain glioma H4 cells experience pressure and thereby investigate the compressive mechanosensors and signaling pathways. Subsequent time‑lapse imaging and wound healing assays confirmed that 12 h of compression significantly increased cell migration, thereby linking compression with enhanced cell motility. Compression upregulated the expression of Piezo1, a mechanosensitive ion channel, and growth differentiation factor 15 (GDF15), a TGF‑β superfamily member. Knockdown experiments targeting PIEZO1 or GDF15 using small interfering RNA resulted in reduced cell motility, with Piezo1 regulating GDF15 expression. Compression also upregulated CTLA4, a critical immune checkpoint protein. The findings of the present study therefore suggest that compression enhances glioma progression by stimulating Piezo1, promoting GDF15 expression and increasing CTLA4 expression. Thus, these findings provide important insights into the influence of mechanical compression on glioma progression and highlight the involvement of the Piezo1‑GDF15 signaling pathway. Understanding tumor responses to mechanical forces in the brain microenvironment may guide the development of targeted therapeutic strategies to mitigate tumor progression and improve patient outcomes.

Background: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies.

Objective: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min.

Methods: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant.

Results: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease.

Conclusion and relevance: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Background: Subjective cognitive decline (SCD), considered a preclinical dementia stage, is less understood in Hispanics, a high-risk group for dementia. We investigated SCD to mild cognitive impairment (MCI) progression risk, as well as baseline and longitudinal features of depressive symptoms, SCD complaints, and objective cognitive performance among Hispanics compared to non-Hispanic Whites (NHW).

Methods: Hispanic (n = 23) and NHW (n = 165) SCD participants were evaluated at baseline and 2-year follow-up. Evaluations assessed function, depressive symptoms, SCD, and objective cognitive performance.

Results: Hispanics were at increased risk of progression to MCI (OR: 6.10, 95% CI 1.09-34.20, P = .040). Hispanic participants endorsed more depressive symptoms at baseline (P = .048) that worsened more longitudinally (OR: 3.16, 95% CI 1.18-8.51, P = .023). Hispanic participants had increased SCD complaints on the Brief Cognitive Rating Scale (BCRS) (β = .40 SE: .17, P = .023), and in specific BCRS domains: concentration (β = .13, SE: .07, P = .047), past memory (β = .13, SE: .06, P = .039) and functional abilities (β = .10, SE: .05, P = .037). In objective cognitive performance, Hispanic ethnicity associated with decline in MMSE (β = -.27, SE: .13, P = .039), MoCA (β = -.80 SE: .34, P = .032), Trails A (β = 2.75, SE: .89, P = .002), Trails B (β = 9.18, SE: 2.71, P = .001) and Guild Paragraph Recall Delayed (β = -.80 SE: .28, P = .005). Conclusions: Hispanic ethnicity associated with a significantly increased risk of 2-year progression of SCD to MCI compared to NHW. This increased risk associated with increased depressive symptoms, distinctive SCD features, and elevated amnestic and non-amnestic objective cognitive decline. This supports further research to refine the assessment of preclinical dementia in this high-risk group.

Occupational therapy practitioners' (OTP's) perceptions of their role in working on the acute postpartum hospital unit are unknown. The objective of this research was to determine the perspectives of OTP's enrolled in a continuing education course to gain competency in providing services to acute postpartum patients. Investigators engaged in a phenomenology consisting of semi-structured interviews with six OTP's working in acute care hospitals preparing to work on the postpartum unit. Three themes emerged from transcripts: (a) Its' Not THAT Different; (b) Willing To Try; and (c) Shifting Focus To Mom. OTPs working in hospitals identified existing skills applicable to working with acute postpartum patients, a need for additional learning to enhance competence, and a desire to focus support for the birthing person to improve maternal outcomes. Hospital onboarding and/or entry-level OTP programs should consider including education on the postpartum population. Future research should focus on program implementation on acute postpartum hospital units.

Objectives: Using "digital inequality" as a conceptual framework, this study evaluates the feasibility and usability of a technology-delivered intervention (an "app") for Alzheimer's and related dementia family caregivers. Time for Living and Caring (TLC) is an on-line intervention that provides virtual coaching and self-administered education and resources. Methods: A sample of family caregivers (n = 163) used the tool for 16 weeks, which included completing the Computer Proficiency Questionnaire (CPQ-12) at baseline. Analyses investigate the relationship between age, CPQ scores, intervention use, appraisal, and caregiver outcomes. Results: Age was inversely associated with CPQ; however, CPQ scores did not have a significant relationship with participant's self-perceived benefits or intervention appraisal. Computer Proficiency Questionnaire scores provided insight regarding research feasibility, with lower scores associated with greater odds of discontinuing engagement. Discussion: CPQ-12 scores can be used as a screening tool to identify those who may need additional support to engage with and benefit from technology-delivered interventions.

This study aimed to evaluate the psychometric characteristics of the Social Phobia Inventory (SPIN) by employing network analysis, confirmatory factor analysis, and the Polytomous Rasch Model. A cross-sectional data set was collected comprising 1,530 participants, with 959 being women and 571 being men. The Bootstrap Exploratory Graph Analysis unveiled the presence of two dimensions, with Items 17, 15, 5, 14, 6, and 9 exhibiting the highest strength centrality index. Notably, the Network Comparison Test indicated no differences in Network Invariance and global strength between the networks of women and men. Furthermore, the confirmatory factor analysis results demonstrated that the two extracted dimensions displayed an acceptable goodness of fit. In addition, the reliability coefficient values were acceptable, exceeding the threshold of 0.70. The Rasch analysis results suggested an overall fit, but some items exhibited overlap, suggesting their potential removal. Furthermore, it was recommended to develop new items to address gaps between existing items, particularly for measuring the lower levels of Social Anxiety Disorder. In conclusion, these findings provide robust evidence supporting the reliability and validity of the SPIN as a tool for measuring Social Anxiety Disorder in Algeria.

Objectives: This literature review aims to assess the current state of the field linking neighborhood environments to later-life health and wellbeing. Methods: We used electronic databases (e.g., PubMed, Google Scholar, and ProQuest) to search for studies published between 2010 and 2022 examining associations between neighborhood built environmental variables and later-life physical, cognitive, mental, and social health outcomes. Results: Among 168 studies reviewed, the majority were quantitative (n = 144) and cross-sectional (n = 122). Neighborhood environmental variables significantly associated with later-life health outcomes included population density/rurality, walkability/street connectivity, access to services and amenities, neighborhood quality and disorder, and parks/green/blue/open space. Neighborhoods operated through behavioral and biological pathways including hazardous exposures, affective states (e.g., stress and restoration), and lifestyle (e.g., exercise, socialization, and diet). Discussion: Neighborhoods and healthy aging research is a burgeoning interdisciplinary and international area of scholarship. Findings can inform upstream community interventions and strengthen clinical care.