Risk factors predicting hospital-acquired pressure injury in adult patients: An overview of reviews.

BACKGROUND: Hospital-acquired pressure injuries remain a significant patient safety threat. Current well-known pressure injury risk assessment tools have many limitations and therefore do not accurately predict the risk of pressure injury development over diverse populations. A contemporary understanding of the risk factors predicting pressure injury in adult hospitalised patients will inform pressure injury prevention and future researchers considering risk assessment tool development may benefit from our summary and synthesis of risk factors. OBJECTIVE: To summarise and synthesise systematic reviews that identify risk factors for hospital-acquired pressure injury development in adult patients. DESIGN: An overview of systematic reviews. METHODS: Cochrane and the Joanna Briggs Institute methodologies guided this overview. The Cochrane library, CINAHL, MEDLINE, and Embase databases were searched for relevant articles published in English from January 2008 to September 2022. Two researchers independently screened articles against the predefined inclusion and exclusion criteria, extracted data and assessed the quality of the included reviews using "a measurement tool to assess systematic reviews" (AMSTAR version 2). Data were categorised using an inductive approach and synthesised according to the recent pressure injury conceptual frameworks. RESULTS: From 11 eligible reviews, 37 risk factors were categorised inductively into 14 groups of risk factors. From these, six groups were classified into two domains: four to mechanical boundary conditions and two to susceptibility and tolerance of the individual. The remaining eight groups were evident across both domains. Four main risk factors, including diabetes, length of surgery or intensive care unit stay, vasopressor use, and low haemoglobin level were synthesised. The overall quality of the included reviews was low in five studies (45 %) and critically low in six studies (55 %). CONCLUSIONS: Our findings highlighted the limitations in the methodological quality of the included reviews that may have influenced our results regarding risk factors. Current risk assessment tools and conceptual frameworks do not fully explain the complex and changing interactions amongst risk factors. This may warrant the need for more high-quality research, such as cohort studies, focussing on predicting hospital-acquired pressure injury in adult patients, to reconsider these risk factors we synthesised. REGISTRATION: This overview was registered with the PROSPERO (CRD42022362218) on 27 September 2022.

Choroidal Melanoma with Ultrasound-Guided Episcleral Brachytherapy: Long-Term Results and Risk of Metastasis.

INTRODUCTION: The aim of this study was to elucidate the long-term outcomes in patients with choroidal melanoma who received episcleral brachytherapy with 125-I seeds; analyse cause-specific survival (CSS), metastasis-free survival (MFS), and local control; and establish the relationship between tumour size and metastases. METHODS: From May 2007 to February 2013, 88 patients classified according to the American Joint Committee on Cancer guidelines underwent ultrasound-guided episcleral brachytherapy with a total prescribed dose of 72.40 Gy to the apex. RESULTS: Among the included cases, 47.7 and 44.3% had a clinical tumour stage of T2 and T3, respectively. With a median follow-up of 84 (range 7-153) months, local control at 5 and 10 years was 100 and 95%, respectively. Among the 88 patients, 9 (10.2%) were enucleated after brachytherapy. Those with T1-T2 and T3-T4 disease had a 10-year CSS of 100 and 87.3%, respectively (p = 0.017). MFS at 5 and 10 years was 100% in those with T1-T2 disease and 92.1 and 83.1% in those with T3-T4, respectively (p = 0.016). Five patients had liver metastases, all of whom had T3-T4 disease. CONCLUSION: Ultrasound-guided episcleral brachytherapy with 125-I seeds yielded excellent local control for choroidal melanoma, with low complication rates and 90% eye preservation. Given the association between tumour stage and liver metastases, which remain the main cause of death, stricter control should be employed for T3-T4 tumours for the early detection and treatment of relapses.

Role of epigenetic m6 A RNA methylation in vascular development: mettl3 regulates vascular development through PHLPP2/mTOR-AKT signaling.

N6 -methyladenosine (m6A) methylation is the most prevalent RNA modification, and it emerges as an important regulatory mechanism of gene expression involved in many cellular and biological processes. However, the role of m6 A methylation in vascular development is not clear. The m6 A RNA methylation is regulated by dynamic interplay among methyltransferases, binding proteins, and demethylases. Mettl3 is a member of the mettl3-mettl14 methyltransferase complex, referred to as writers that catalyze m6A RNA methylation. Here, we used CRISPR-Cas9 genome editing to develop two lines of knockout (KO) zebrafish for mettl3. Heterozygous mettl3+/- KO embryos show defective vascular development, which is directly visible in fli-EGFP and flk-EGFP zebrafish. Alkaline phosphatase staining and whole mount in situ hybridization with cdh5, and flk markers demonstrated defective development of intersegmental vessels (ISVs), subintestinal vessels (SIVs), interconnecting vessels (ICVs) and dorsal longitudinal anastomotic vessels (DLAV) in both heterozygous mettl3+/- and homozygous mettl3-/- KO zebrafish embryos. Similar phenotypes were observed in zebrafish embryos with morpholino knockdown (KD) of mettl3; however, the vascular defects were rescued fully by overexpression of constitutively active AKT1. KD of METTL3 in human endothelial cells inhibited cell proliferation, migration, and capillary tube formation. Mechanistically, mettl3 KO and KD significantly reduced the levels of m6 A RNA methylation, and AKT phosphorylation (S473) by an increase in the expression of phosphatase enzyme PHLPP2 and reduction in the phosphorylation of mTOR (S2481), a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. These data suggest that m6 A RNA methylation regulates vascular development via PHLPP2/mTOR-AKT signaling.

Potato wound-healing tissues: A rich source of natural antioxidant molecules with potential for food preservation.

The need for safe, effective preservatives is a prominent issue in the food and drug industries, reflecting demand for natural alternatives to synthetic chemicals viewed as harmful to consumers and the environment. Thus, this study determined the identities and scavenging capacities of antioxidant metabolites produced as a response to potato tuber wounding, using activity-guided fractionation of polar extracts from a Yukon Gold cultivar that had previously exhibited exceptionally high radical-scavenging activity. Activity-guided fractionation using the ABTS(+) radical scavenging assay and LC-MS with TOF-MS for compositional analysis of the most potent antioxidant fractions yielded identification of nine constituents: coumaroylputrescine; feruloylquinic acid; isoferuloylputrescine; ferulic acid; 22,25-dimethoxy-3-[[2,3,4-tri-O-methyl-6-O-(2,3,4,6-tetra-O-methyl-ß-d-glucopyranosyl)-ß-d-glucopyranosyl]oxy]-(3ß)-lanost-9(11)-en-24-one; 4-(2Z)-2-decen-1-yl-5-[1-(4-hydroxyphenyl)decyl]-1,2-benzenediol; 8-[(2E)-3,7-dimethyl-2,6-octadien-1-yl]-5-hydroxy-2,8-dimethyl-6-(3-methyl-2-buten-1-yl)-2H-1-benzopyran-4,7(3H,8H)-dione; 3-[(2-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl)oxy]-20-[(6-O-ß-d-xylopyranosyl-ß-d-glucopyranosyl)oxy]-dammar-24-en-19-al; (3ß)-28-oxo-28-(phenylmethoxy)oleanan-3-yl 2-O-ß-d-galactopyranosyl-3-O-(phenylmethyl)-, butyl ester ß-d-glucopyranosiduronic acid. A positive correlation was observed between the scavenging activities and the polarities of the active fractions. The antioxidant capacities of the fractions were also characterised by monitoring the activity throughout a 45-minute assay period.

Genetic variation in insulin-induced kinase signaling.

Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20-fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis-acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance.

Defensive Armor of Potato Tubers: Nonpolar Metabolite Profiling, Antioxidant Assessment, and Solid-State NMR Compositional Analysis of Suberin-Enriched Wound-Healing Tissues.

The cultivation, storage, and distribution of potato tubers are compromised by mechanical damage and suboptimal healing. To investigate wound-healing progress in cultivars with contrasting russeting patterns, metabolite profiles reported previously for polar tissue extracts were complemented by GC/MS measurements for nonpolar extracts and quantitative (13)C NMR of interfacial solid suspensions. Potential marker compounds that distinguish cultivar type and wound-healing time point included fatty acids, fatty alcohols, alkanes, glyceryl esters, α,ω-fatty diacids, and hydroxyfatty acids. The abundant long-chain fatty acids in nonpolar extracts and solids from the smooth-skinned Yukon Gold cultivar suggested extensive suberin biopolymer formation; this hypothesis was supported by high proportions of arenes, alkenes, and carbonyl groups in the solid and among the polar markers. The absence of many potential marker classes in nonpolar Atlantic extracts and interfacial solids suggested a limited extent of suberization. Modest scavenging activities of all nonpolar extracts indicate that the majority of antioxidants produced in response to wounding are polar.

ADAR regulates RNA editing, transcript stability, and gene expression.

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine, which is then recognized as guanosine. To study the role of ADAR proteins in RNA editing and gene regulation, we sequenced and compared the DNA and RNA of human B cells. Then, we followed up the findings experimentally with siRNA knockdown and RNA and protein immunoprecipitations. The results uncovered over 60,000 A-to-G editing sites and several thousand genes whose expression levels are influenced by ADARs. Of these ADAR targets, 90% were identified. Our results also reveal that ADAR regulates transcript stability and gene expression through interaction with HuR (ELAVL1). These findings extend the role of ADAR and show that it cooperates with other RNA-processing proteins to regulate the sequence and expression of transcripts in human cells.