Carltoncrabtree6986
Epigenetic reprogramming using DNA demethylating drugs is a promising approach for cancer therapy, but its efficacy is highly dependent on the dosing regimen. Low-dose treatment for a prolonged period shows a remarkable therapeutic efficacy, despite its small demethylating effect. Here, we aimed to explore the mechanisms of how such low-dose treatment shows this remarkable efficacy by focusing on epigenetic reprograming at the single-cell level.
Expression profiles in HCT116 cells treated with decitabine (DAC) were analyzed by single-cell RNA-sequencing (scRNA-seq). Functional consequences and DNA demethylation at the single-cell level were analyzed using cloned HCT116 cells after DAC treatment.
scRNA-seq revealed that DAC-treated cells had highly diverse expression profiles at the single-cell level, and tumor-suppressor genes, endogenous retroviruses, and interferon-stimulated genes were upregulated in random fractions of cells. DNA methylation analysis of cloned HCT116 cells revealed that, while only partial reduction of DNA methylation levels was observed in bulk cells, complete demethylation of specific cancer-related genes, such as cell cycle regulation, WNT pathway, p53 pathway, and TGF-β pathway, was observed, depending upon clones. Functionally, a clone with complete demethylation of CDKN2A (p16) had a larger fraction of cells with tetraploid than parental cells, indicating induction of cellular senescence due to normalization of cell cycle regulation.
Epigenetic reprogramming of specific cancer-related pathways at the single-cell level is likely to underlie the remarkable efficacy of low-dose DNA demethylating therapy.
Epigenetic reprogramming of specific cancer-related pathways at the single-cell level is likely to underlie the remarkable efficacy of low-dose DNA demethylating therapy.
Disruption of the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis.
Abdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman's correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations betweeess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.
These findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and insulin resistance in South African women. Additional studies are required to assess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.
Over the past decade, hospitals in many countries, including Israel, have undergone an accreditation process aimed at improving the quality of services provided. This process also refers to the protection and promotion of patients' rights. However, reviewing the criteria and content included in this category in the Israeli context reveals definitions and implications that differ from those presented by the law - specifically the Patient's Rights Act 1995. Moreover, the rights included in it are not necessarily equally represented in other legislation.
This study seeks to examine the question of whether and to what extent the scope, contents, and definitions of patients' rights in the JCI Standards are similar to or different from patients' rights as they are addressed and protected in national legislation. The article provides a comparison and examination of the different regulatory frameworks of patients' rights, especially those in the accreditation of healthcare institution and legislation, analyzes th instrumental - for broader policy purposes, especially in the area of patients' rights and the rights of patients' families - but also calls for a more general examination of the concept of patients' rights in health policies and its contribution to the quality of health services. Reference to patients' rights in accreditation of healthcare institutions may promote and enhance this concept and contribute to the delivery of care, thereby complementing a lacuna in the law.
Plantar fasciopathy (PF) is a very common disease, affecting about 1/10 people in their lifetime. Platelet-rich plasma (PRP) had been demonstrated to be useful in achieving helpful effects for plantar fasciopathy. The purpose of this study was to compare the pain and functional outcomes between PRP and corticosteroid (CS) or placebo for plantar fasciopathy through meta-analysis and provide the best evidence.
Literature was searched systematically to explore related studies that were published in Cochrane Library, PubMed, Embase, Medline, SpringerLink, OVID, and ClinicalTrials.gov . Articles regarding comparative research about the outcomes of PRP therapy and CS or placebo injection were selected. Data of pain and functional outcomes was extracted and imported into Reviewer Manager 5.3 to analyze.
Thirteen RCTs were included and analyzed. Analysis results showed significant superiority of PRP in outcome scores when compared with CS (VAS MD = - 0.85, P < 0.0001, I
= 85%; AOFAS MD = 10.05, P < 0.0001, I
= 85%), whereas there is no statistical difference in well-designed double-blind trials (VAS MD = 0.15, P = 0.72, I
= 1%; AOFAS MD = 2.71, P = 0.17, I
= 0%). In the comparison of the PRP and the placebo, the pooled mean difference was - 3.76 (P < 0.0001, 95% CI = - 4.34 to - 3.18).
No superiority of PRP had been found in well-designed double-blind studies, whereas it is implied that the outcomes of PRP are better than placebo based on available evidence.
No superiority of PRP had been found in well-designed double-blind studies, whereas it is implied that the outcomes of PRP are better than placebo based on available evidence.
Lived experience research is conducted by people who have experience of mental health issues and is therefore better placed than more traditional research to illuminate participants' experiences. Findings that focus on identifying enablers of recovery from a lived experience perspective have the potential to assist people in their recovery process. However, this lived experience research is often difficult to find, access and interpret. BLU9931 mouse We co-produced user-friendly and engaging resources to disseminate findings from six lived experience research studies. This paper seeks to answer the research questions a) Did exposure to lived experience research increase hopefulness for participants?; and b) How else did interacting with lived experience research resources influence participants' lives?
Thirty-eight participants were introduced to four resources of their choosing by peer workers over a four-week period. The helpfulness of resources was evaluated using mixed methods, including a quasi-experimental analysis of change in hope, an anonymous survey and in-depth interviews.
Findings indicated that the resources promoted hope, but that increases in hopefulness may not be seen immediately. Other impacts include that the resources encouraged helpful activities; provided a positive experience; increased valued knowledge; encouraged people to reflect on their journey and think constructively about mental health issues; helped people to feel less alone; and assisted people to explain their situation to others.
The research suggests the potential usefulness of lived experience research resources, presented in user-friendly formats, in the lives of people who experience mental health issues and implies a need to nurture this type of research.
The research suggests the potential usefulness of lived experience research resources, presented in user-friendly formats, in the lives of people who experience mental health issues and implies a need to nurture this type of research.
Work-related eye injury causes significant vision loss. Most of these injuries are preventable with appropriate eye safety practices. We aimed to study industrial workers' perceptions of Personal Protective Eyewear (PPE) and its usage in a high income developing country.
A field-based cross-sectional study in small-scale industrial entities was performed in Al-Ain City, UAE during the period of October 2018 to June 2019. Five hundred workers completed a pretested structured questionnaire. Data on demographics, occupational history, work hazard awareness, and PPE usage at their work place were collected.
The workers were experienced, with a median of 15 years in practice. The majority (80%) learned their work skills through apprenticeship (i.e., on-the-job) training. Most (85%) were involved with activities presenting eye injury risk, and were highly aware of this. None of the workers used safety goggles or glasses all the time for activities that need PPE usage. Five percent never used PPE in the workplace. The main reason for not using PPE was the work demands (95%) and poor vision through the lenses (75%). Young age and less work experience were associated with less PPE usage (P < 0.0001). Wearing prescription spectacles had a positive correlation with usage of safety goggles (P = 0.005) and a negative correlation with welding helmet usage (P < 0.0001).
There was a high level of awareness about the value of PPE in the workplace which was not translated into real practice. Educational programs promoting eye safety practices and proper PPE usage should be adopted by workers in small-scale industrial settings.
There was a high level of awareness about the value of PPE in the workplace which was not translated into real practice. Educational programs promoting eye safety practices and proper PPE usage should be adopted by workers in small-scale industrial settings.
Aedes spp. are responsible for the transmission of many arboviruses, which contribute to rising human morbidity and mortality worldwide. The Aedes aegypti mosquito is a main vector for chikungunya, dengue and yellow fever infections, whose incidence have been increasing and distribution expanding. This vector has also driven the emergence of the Zika virus (ZIKV), first reported in Africa which spread rapidly to Asia and more recently across the Americas. During the outbreak in the Americas, Cape Verde became the first African country declaring a Zika epidemic, with confirmed cases of microcephaly. Here we investigate the prevalence of ZIKV and dengue (DENV) infected Ae. aegypti mosquitoes in the weeks following the outbreak in Cape Verde, and the presence of insecticide resistance in the circulating vector population. Genetic diversity in the mosquito population was also analysed.
From August to October 2016, 816 Ae. aegypti mosquitoes were collected in several locations across Praia, Cape Verde, the major hot spot of reported ZIKV cases in the country.
