Extracellular vesicles and their effect on vascular haemodynamics: a systematic review.

Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 109-1010 circulating EVs/mL in the plasma of healthy individuals derived from various sources. While the effect of EVs on vascular haemodynamic parameters will be dependent on the details of the model studied, we systematically searched and summarized current literature to find patterns in how exogenously injected EVs affected vascular haemodynamics. Under homoeostatic conditions, evidence from wire and pressure myography data demonstrate that injecting isolated EVs derived from cell types found in blood and blood vessels resulted in the impairment of vasodilation in blood vessels ex vivo. Impaired vasodilation was also observed in rodents receiving intravenous injections of human plasma EVs from cardiovascular diseases including valvular heart disease, acute coronary syndrome, myocardial infarction and end stage renal disease. When EVs were derived from models of metabolic syndromes, such as diabetes, these EVs enhanced vasoconstriction responses in blood vessels ex vivo. There were fewer publications that assessed the effect of EVs in anaesthetised or conscious animals to confirm whether effects on the vasculature observed in ex vivo studies translated into alterations in vascular haemodynamics in vivo. In the available conscious animal studies, the in vivo data did not always align with the ex vivo data. This highlights the importance of in vivo work to determine the effects of EVs on the integrative vascular haemodynamics.

Using saliva epigenetic data to develop and validate a multivariable predictor of esophageal cancer status.

Background: Salivary epigenetic biomarkers may detect esophageal cancer. Methods: A total of 256 saliva samples from esophageal adenocarcinoma patients and matched volunteers were analyzed with Illumina EPIC methylation arrays. Three datasets were created, using 64% for discovery, 16% for testing and 20% for validation. Modules of gene-based methylation probes were created using weighted gene coexpression network analysis. Module significance to disease and gene importance to module were determined and a random forest classifier generated using best-scoring gene-related epigenetic probes. A cost-sensitive wrapper algorithm maximized cancer diagnosis. Results: Using age, sex and seven probes, esophageal adenocarcinoma was detected with area under the curve of 0.72 in discovery, 0.73 in testing and 0.75 in validation datasets. Cancer sensitivity was 88% with specificity of 31%. Conclusion: We have demonstrated a potentially clinically viable classifier of esophageal cancer based on saliva methylation.

Development and validation of a multivariable risk factor questionnaire to detect oesophageal cancer in 2-week wait patients.

INTRODUCTION: Oesophageal cancer is associated with poor health outcomes. Upper GI (UGI) endoscopy is the gold standard for diagnosis but is associated with patient discomfort and low yield for cancer. We used a machine learning approach to create a model which predicted oesophageal cancer based on questionnaire responses. METHODS: We used data from 2 separate prospective cross-sectional studies: the Saliva to Predict rIsk of disease using Transcriptomics and epigenetics (SPIT) study and predicting RIsk of diSease using detailed Questionnaires (RISQ) study. We recruited patients from National Health Service (NHS) suspected cancer pathways as well as patients with known cancer. We identified patient characteristics and questionnaire responses which were most associated with the development of oesophageal cancer. Using the SPIT dataset, we trained seven different machine learning models, selecting the best area under the receiver operator curve (AUC) to create our final model. We further applied a cost function to maximise cancer detection. We then independently validated the model using the RISQ dataset. RESULTS: 807 patients were included in model training and testing, split in a 70:30 ratio. 294 patients were included in model validation. The best model during training was regularised logistic regression using 17 features (median AUC: 0.81, interquartile range (IQR): 0.69-0.85). For testing and validation datasets, the model achieved an AUC of 0.71 (95% CI: 0.61-0.81) and 0.92 (95% CI: 0.88-0.96) respectively. At a set cut off, our model achieved a sensitivity of 97.6% and specificity of 59.1%. We additionally piloted the model in 12 patients with gastric cancer; 9/12 (75%) of patients were correctly classified. CONCLUSIONS: We have developed and validated a risk stratification tool using a questionnaire approach. This could aid prioritising patients at high risk of having oesophageal cancer for endoscopy. Our tool could help address endoscopic backlogs caused by the COVID-19 pandemic.

First trimester placental extracellular vesicles likely contribute to the vasodilation of maternal resistance arteries in normal pregnancy.

During the first trimester of pregnancy, there is a large decrease in systemic vascular resistance (SVR) which coincides temporally with increasing extrusion of extracellular vesicles (EVs) from the placenta. We hypothesized that placental EVs may be one of the mechanisms contributing to maternal vasodilation. Macro-, micro-, nano-EVs from human first trimester placenta, or control injections containing EVs derived from fresh culture media, were injected into pregnant mice at day 12.5. After 30 min or 24 h, second order resistance arteries assessed for their reactivity to various vasomodulators. Placental EVs induced an anti-constrictive, pro-vasodilatory effect in maternal resistance arteries compared to control injections after 24 h suggesting that placental EVs may contribute to the maternal vasodilation during pregnancy.

Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort.

BACKGROUND: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. METHODS: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. RESULTS: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001). CONCLUSION: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. CLINICAL TRIAL REGISTRATION: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.

Plasma sodium and subclinical left atrial enlargement in chronic kidney disease.

BACKGROUND: Left atrial enlargement (LAE) reflects diastolic dysfunction and predicts mortality in end-stage renal disease patients. However, little is known of its prevalence and factors associated with subclinical LAE in earlier stages of chronic kidney disease (CKD). METHODS: We conducted a prospective, cross-sectional study in 261 Stage 3-5 non-dialysis CKD patients without symptomatic cardiovascular disease with two-dimensional echocardiography performed to estimate left atrial volume index and other cardiac parameters. RESULTS: One hundred and nine (41.8%) patients had LAE. Mild and moderate/severe LAEs were observed in 22.9 and 41.3% of patients with left ventricular (LV) hypertrophy (n = 109) versus 13.2 and 12.5% of patients with no LV hypertrophy (n = 152), respectively (P < 0.001). On univariate analysis, plasma sodium concentration showed a significant association with LAE [odds ratio (OR) 1.22, 95% confidence interval (95% CI) 1.09-1.37; P = 0.001]. In the stepwise multiple logistic regression, plasma sodium concentration emerged as one of the most significant factors associated with LAE (adjusted OR 1.29, 95% CI 1.14-1.47; P < 0.001]. Its significance was well maintained (adjusted OR 1.23, 95% CI 1.07-1.43; P = 0.005) when including LV mass and volume index and N-terminal pro-brain natriuretic peptide in the model, while blood haemoglobin and systolic blood pressure were displaced. CONCLUSIONS: This study for the first time alerted to a very high prevalence of subclinical LAE and reported a strong novel, independent relationship between plasma sodium concentration and subclinical LAE in Stage 3-5 CKD patients. Longitudinal studies are needed to establish causality between high plasma sodium concentration and LAE and their usefulness as therapeutic targets in CKD.

Framework for adopting a problem-based learning approach in a simulated clinical setting.

The problem-based learning (PBL) approach applied in the clinical setting is different from that applied in the classroom setting. This study analyzed a learning and teaching episode in a simulated clinical situation using the PBL approach. Conversation analysis was used to examine the scenario. Data analysis revealed six key manifestations of this learning arrangement: collection of information, data analysis, formulation of hypotheses, validation, discussion and reflection, and learning synthesis. The simulated clinical environment provided realism in learning and allowed students to experience a full range of learning issues within a short time frame. Problem-based learning was a deliberate approach that helped students achieve the following learning outcomes: patient-focused care, student-directed learning, inductive learning, and translation of theoretical knowledge into practical information. Learning was further enhanced with postsimulation self-evaluation and peer analyses. The incorporation of the PBL approach can bring out the optimal effects in a simulated learning environment.

Fostering maturity for senior nursing students: a pre-graduation clinical placement.

BACKGROUND: There is considerable literature on graduates' role transition to registered nurse from the employer's perspective. Few studies have discussed issues and strategies related to nursing students' preparedness. In response to the Bachelor of Nursing (Honours) senior nursing students' needs in terms of role transition, a pre-graduation clinical placement (PGCP) was implemented. AIM: The aim of this paper is to report the learning experiences and outcomes of the PGCP. METHODS: Both quantitative and qualitative approaches were used. All students (n=37) and preceptors (n=33) involved in the PGCP consented to participate in summer 2002. The data included: students' and preceptors' appraisal of pre- and post-Inventory for Nursing Competencies (INC), students' formative and summative reflective journals, and post-PGCP focus group interviews. Paired t-tests were done to compare students' and preceptors' pre- and post-INC scores, and thematic analyses were carried out for qualitative data. RESULTS: There were statistically significant improvements in students' INC. Three themes - learning to work with ward nurses and preceptors, learning total aspects of care, and acting as RNs - were revealed. CONCLUSION: The success of the PGCP demonstrates the promising outcome of a long consolidating clinical block prior to graduation in fostering maturity for role transition.

Metal contamination in urban, suburban, and country park soils of Hong Kong: a study based on GIS and multivariate statistics.

The urban environment quality is of vital importance as the majority of people now live in cities. Due to the continuous urbanisation and industrialisation in many parts of the world, metals are continuously emitted into the terrestrial environment and pose a great threat on human health. An extensive survey was conducted in the highly urbanised and commercialised Hong Kong Island area (80.3 km2) of Hong Kong using a systematic sampling strategy of five soil samples per km2 in urban areas and two samples per km2 in the suburban and country park sites (0-15 cm). The analytical results indicated that the surface soils in urban and suburban areas are enriched with metals, such as Cu, Pb, and Zn. The Pb concentration in the urban soils was found to exceed the Dutch target value. The statistical analyses using principal component analysis (PCA) and cluster analysis (CA) showed distinctly different associations among trace metals and the major elements (Al, Ca, Fe, Mg, Mn) in the urban, suburban, and country park soils. Soil pollution maps of trace metals (Cd, Co, Cr, Cu, Ni, Pb, and Zn) in the surface soils were produced based on geographical information system (GIS) technology. The hot-spot areas of metal contamination were mainly concentrated in the northern and western parts of Hong Kong Island, and closely related to high traffic conditions. The Pb isotopic composition of the urban, suburban, and country park soils showed that vehicular emissions were the major anthropogenic sources for Pb. The 206Pb/207Pb and 208Pb/207Pb ratios in soils decreased as Pb concentrations increased in a polynomial line (degree=2).

A narrative inquiry into the Hong Kong Chinese adults' concepts of health through their cultural stories.

BACKGROUND: Abundant studies have investigated how health concepts held by individuals shape and are shaped by psychosocial and cultural factors, though many were limited to the conceptual level. The meaning and significance of health behaviours are better understood as an expression of something occurring over time. OBJECTIVES: This narrative study explores how Hong Kong Chinese adults understand the meaning of health and the ways by which they construct and express these meanings in their lives. Additionally, by recognizing the central features of temporality, personal-social interactions within a place/culture in narrative thinking, this narrative inquiry may help health-care professionals to revisit the meaning of health promotion within the context of an individual's life situation. METHODS: Five participants were recruited for the study. Data were collected through a series of audio-taped unstructured interviews and conversations with each participant. RESULTS: Findings underscore several features of participants' concepts and expressions of health: the significance of Confucian teachings on roles and responsibilities, Eastern view of self, Western biomedical orientation, and Hong Kong's unique work culture. Their responses not only express the attitudes and behaviours of individuals, but also the ways they engage in their constructed identity. CONCLUSION: Participants' concepts of health evolved over time according to the personal meanings attached to them at various life stages. While participants recognized the interconnectedness of the mind and body, the physical foci of traditional Western medicine remained salient in their health stories. Furthermore, there is a clear delineation of personal management of the psychological health and professional management of physical health.