Medical device-related pressure injury from compression therapy.

The use of compression therapy is known to be effective in the management of patients with venous leg ulceration and is commonly recommended as a first-line treatment. A rare but known complication of compression therapy is pressure damage to the limb, also referred to as bandage damage, which should be categorised as a medical device-related pressure injury. Patients should receive a comprehensive, holistic assessment before any compression therapy is applied. Risk factors for compression therapy injury include peripheral arterial disease, older age, fragile skin, pronounced bony prominences or tendons, calf atrophy, foot drop, neuropathy/absent sensation, limited movement, cognitive impairment and receiving end of life care. Risks can be mitigated through a variety of approaches, and practitioners should be aware that these can change depending on the patient's condition. A community improvement initiative, illustrated with a case study, introduced a clinical pathway that can facilitate the identification and management of patients who are at risk of developing pressure injuries as a result of compression therapy.

HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma.

BACKGROUND: Metabolic changes in tumour cells are used in clinical imaging and may provide potential therapeutic targets. Human papillomavirus (HPV) status is important in classifying head and neck cancers (HNSCC), identifying a distinct clinical phenotype; metabolic differences between these HNSCC subtypes remain poorly understood. METHODS: We used RNA sequencing to classify the metabolic expression profiles of HPV+ve and HPV-ve HNSCC, performed a meta-analysis on FDG-PET imaging characteristics and correlated results with in vitro extracellular flux analysis of HPV-ve and HPV+ve HNSCC cell lines. The monocarboxylic acid transporter-1 (MCT1) was identified as a potential metabolic target and tested in functional assays. RESULTS: Specific metabolic profiles were associated with HPV status, not limited to carbohydrate metabolism. There was dominance of all energy pathways in HPV-negative disease, with elevated expression of genes associated with glycolysis and oxidative phosphorylation. In vitro analysis confirmed comparative increased rates of oxidative phosphorylation and glycolysis in HPV-negative cell lines. PET SUV(max) scores however were unable to reliably differentiate between HPV-positive and HPV-negative tumours. MCT1 expression was significantly increased in HPV-negative tumours, and inhibition suppressed tumour cell invasion, colony formation and promoted radiosensitivity. CONCLUSION: HPV-positive and negative HNSCC have different metabolic profiles which may have potential therapeutic applications.

How do microRNAs affect vascular smooth muscle cell biology?

PURPOSE OF REVIEW: Control of vascular smooth muscle cell (VSMC) phenotype is essential in the development and maintenance of a healthy vasculature. Acquisition of a synthetic, proproliferative phenotype by VSMCs following vascular insult is central to neointimal formation and the development of vascular pathology. MicroRNAs (miRNAs) are relatively recently discovered negative regulators of gene expression and act at the post-transcriptional level. MiRNAs have the potential to control VSMC phenotype. In this review, we discuss the recent findings on how miRNAs influence VSMC biology and acute vascular pathology. RECENT FINDINGS: MiRNAs play an important role in the gene regulation by growth factors and downstream transcription factors involved in VSMC phenotypic control and deregulation. Recent studies have revealed miRNAs that are involved in VSMC regulation and further identified several target genes which are implicated in VSMC pathobiology, highlighting new disease mechanisms. Paracrine miRNA-regulated crosstalk between endothelial and VSMCs has also been demonstrated, revealing a novel mechanism through which vascular cells communicate in health and disease. SUMMARY: MiRNAs appear to play a major role in the capability of VSMCs to phenotypically switch from a contractile to a synthetic state. Altering miRNA expression levels can prevent and even reverse the acquisition of VSMC synthetic phenotype in vivo and reduce neointimal formation, thereby implicating miRNAs as exciting future therapeutic targets for vascular proliferative disease.

Ad5:Ad48 hexon hypervariable region substitutions lead to toxicity and increased inflammatory responses following intravenous delivery.

The development of adenoviral vectors for intravascular (i.v.) delivery will require improvements to their in vivo safety and efficacy. The hypervariable regions (HVRs) of the Ad5 hexon are a target for neutralizing antibodies, but also interact with factor X (FX), facilitating hepatocyte transduction. Ad48, a species D adenovirus, does not bind FX and has low seroprevalence. Therefore, it has been suggested that Ad5HVR48(1-7), a hexon-chimeric vector featuring the seven HVRs from Ad48, should display advantageous properties for gene therapy, by evading pre-existing Ad5 immunity and blocking FX interactions. We investigated the in vivo biodistribution of Ad5, Ad5HVR48(1-7), and Ad48 following i.v. delivery. Ad5HVR48(1-7) displayed reduced hepatocyte transduction and accumulation in Kupffer cells (KCs), but triggered a robust proinflammatory response, even at relatively low doses of vector. We detected elevated serum transaminases (48 hours) and increased numbers of periportal CD11b(+)/Gr-1(+) cells in the livers of Ad5HVR48(1-7)-treated animals following i.v., but not intramuscular (i.m.), delivery. In contrast, Ad48 did not elevate transaminases or result in the accumulation of CD11b(+)/Gr-1(+) cells. Collectively, these findings suggest that substantial hexon modifications can lead to unexpected properties which cannot be predicted from parental viruses. Therefore, refined mutations may be preferential for the successful development of targeted vector systems which require i.v. administration.

miR-21 and miR-214 are consistently modulated during renal injury in rodent models.

Transforming growth factor (TGF)-ß is one of the main fibrogenic cytokines that drives the pathophysiology of progressive renal scarring. MicroRNAs (miRNAs) are endogenous non-coding RNAs that post-transcriptionally regulate gene expression. We examined the role of TGF-ß-induced expression of miR-21, miRNAs in cell culture models and miRNA expression in relevant models of renal disease. In vitro, TGF-ß changed expression of miR-21, miR-214, and miR-145 in rat mesangial cells (CRL-2753) and miR-214, miR-21, miR-30c, miR-200b, and miR-200c during induction of epithelial-mesenchymal transition in rat tubular epithelial cells (NRK52E). miR-214 expression was robustly modulated in both cell types, whereas in tubular epithelial cells miR-21 was increased and miR-200b and miR-200c were decreased by 58% and 48%, respectively, in response to TGF-ß. TGF-ß receptor-1 was found to be a target of miR-200b/c and was down-regulated after overexpression of miR-200c. To assess the differential expression of these miRNAs in vivo, we used the anti-Thy1.1 mesangial glomerulonephritis model and the unilateral ureteral obstruction model in which TGF-ß plays a role and also a genetic model of hypertension, the stroke-prone spontaneously hypertensive rat with and without salt loading. The expressions of miR-214 and miR-21 were significantly increased in all in vivo models, showing a possible miRNA signature of renal damage despite differing causes.