Effect of Pseudomonas colonisation on lower limb venous ulcer healing: a systematic review.

OBJECTIVE: Pseudomonas aeruginosa is a Gram-negative bacillus that commonly colonises lower limb venous ulcers. Its effects on venous ulcer healing are widely debated. It produces exotoxins and elastase, as well as forming biofilms in hard-to-heal wounds. It is postulated that these virulence factors lead to slower healing times in patients with lower limb venous ulcers colonised with Pseudomonas. This review aimed to summarise the available evidence pertaining to this topic. METHOD: A systematic review was performed in August 2019, where the Pubmed, Cochrane and Embase databases were searched for relevant literature according to PRISMA guidelines. Retrospective and prospective studies examining the effect of Pseudomonas colonisation on any measure of ulcer healing were included. RESULTS: Some 282 articles were screened, of which seven studies including 491 patients were ultimately included for analysis. Of these, no study demonstrated a significant association between Pseudomonas colonisation and delayed healing of venous ulcers. In five of the seven studies, the effect of Pseudomonas aeruginosa on initial ulcer size at presentation was recorded. CONCLUSION: All the studies demonstrated an association between ulcer size and the presence of Pseudomonas aeruginosa. While Pseudomonas aeruginosa may colonise larger ulcers or those with a worse prognosis, no evidence was found to support the hypothesis that this colonisation had a negative impact on lower limb venous ulcer healing.

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants.

BACKGROUND AND AIMS: Atherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification. METHODS AND RESULTS: Clinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (rs = -0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (rs = -0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within excised carotid specimens (rs = -0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups. CONCLUSION: Correlations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.

Correlating Ex Vivo Carotid Calcification Measurements With Cerebrovascular Symptoms: A Proof-of-Concept Study.

BACKGROUND AND PURPOSE: The purpose of this study is to examine the ability of ex vivo derived Agatston, Volume, and Density-Volume calcium scores or calcium density measurements to differentiate between carotid plaques based on preoperative cerebrovascular symptomatology. METHODS: Thirty-eight carotid plaques were acquired from standard endarterectomy. Micro-computed tomography was performed on the ex vivo samples. Image series were downsampled to represent the resolution of clinical multidetector computed tomography. Agatston, Volume, and Density-Volume carotid calcium scores were then calculated using coronary methodologies. The fractions of low- and high-density calcification were also determined. RESULTS: The coronary calcium scores could not differentiate between carotid plaques from asymptomatic versus symptomatic patients. However, plaques from asymptomatic patients contained significantly lower fractions of low-density calcification and higher fractions of high-density calcification. CONCLUSIONS: Screening for carotid calcium density in noncontrast computed tomography could reflect plaque stability.

Memory flexibility training for autobiographical memory as an intervention for maintaining social and mental well-being in older adults.

Autobiographical memory specificity (AMS) reduces with increasing age and is associated with depression, social problem-solving and functional limitations. However, ability to switch between general and specific, as well as between positive and negative retrieval, may be more important for the strategic use of autobiographical information in everyday life. Ability to switch between retrieval modes is likely to rely on aspects of executive function. We propose that age-related deficits in cognitive flexibility impair AMS, but the "positivity effect" protects positively valenced memories from impaired specificity. A training programme to improve the ability to flexibly retrieve different types of memories in depressed adults (MemFlex) was examined in non-depressed older adults to determine effects on AMS, valence and the executive functions underlying cognitive flexibility. Thirty-nine participants aged 70+ (MemFlex, n = 20; control, n = 19) took part. AMS and the inhibition aspect of executive function improved in both groups, suggesting these abilities are amenable to change, although not differentially affected by this type of training. Lower baseline inhibition scores correlated with increased negative, but not positive AMS, suggesting that positive AMS is an automatic process in older adults. Changes in AMS correlated with changes in social problem-solving, emphasising the usefulness of AMs in a social environment.

Moving from the unknown to the known: a multidisciplinary approach to the identification of skeletal remains from Sandy Point, Australia.

When human remains are inadvertently located, case-related circumstantial information is used to generate an identification hypothesis, and the preservation of the remains typically informs which identification methods may then be used to validate that hypothesis. What happens, however, when there is no contextual information to generate an identification hypothesis? This paper presents the case of a near-complete human skeleton discovered at Sandy Point in Victoria, Australia. The circumstances of the case did not facilitate an identification hypothesis, and with no hypothesis to triage the identification process, all possible identification methods were employed. Preservation of the individual meant neither a visual nor a fingerprint identification was possible, and the lack of an identification hypothesis meant there was no antemortem reference data to compare with the postmortem DNA or dental information. Consequently, in addition to historical research, novel methods, such as radiocarbon dating and genetic intelligence, were utilized to complement information provided by the forensic anthropology and odontology analyses, which ultimately resulted in the identification. This example highlights the complexity of cases of unidentified skeletal remains and emphasizes the fact that identification is a process that necessarily requires a multidisciplinary and collaborative approach. Key points: Human skeletal remains were recovered from Sandy Point, Victoria.The absence of circumstantial information and the poor preservation (i.e. skeletonized) of the remains precluded the formation of an identification hypothesis, rendering the identification process complex.Only through the integration of anthropology, odontology, molecular biology, radiocarbon dating, historical research, and genealogy were the remains able to be identified as Mr. Christopher Luke Moore, who drowned in 1928.Human identification is a process that necessarily requires a multidisciplinary and collaborative approach.

Microindentation of fresh soft biological tissue: A rapid tissue sectioning and mounting protocol.

Microindentation of fresh biological tissues is necessary for the creation of 3D biomimetic models that accurately represent the native extracellular matrix microenvironment. However, tissue must first be precisely sectioned into slices. Challenges exist in the preparation of fresh tissue slices, as they can tear easily and must be processed rapidly in order to mitigate tissue degradation. In this study, we propose an optimised mounting condition for microindentation and demonstrate that embedding tissue in a mixture of 2.5% agarose and 1.5% gelatin is the most favourable method of tissue slice mounting for microindentation. This protocol allows for rapid processing of fresh biological tissue and is applicable to a variety of tissue types.

Clinical research stakeholders' experiences of clinical research during COVID-19: a qualitative study.

BACKGROUND: The COVID-19 pandemic created a complex high-risk clinical research environment with clinical research activities significantly impacted. Clinical research stakeholders adapted rapidly to new clinical practices; PPE, infection control policies, all while engaging with a more unwell patient demographic. The aim of this study is to explore the experiences of conducting clinical research during COVID-19 with clinical research stakeholders. METHODS: This qualitative study of semi-structured interviews conducted with clinical research stakeholders in an acute Hospital setting across a variety of disciplines; Consultant Geriatrician, Clinical Research Nurse, Occupational Therapy, Physiotherapy. Interviews were fully transcribed prior to reflexive thematic analysis. NVivo software was used to support data management and analysis. RESULTS: Three main themes were produced; (1) The challenging COVID-19 clinical research landscape, (2) COVID-19 clinical research communication barriers, and (3) Adaptations and learnings from clinical research during COVID-19. CONCLUSIONS: This study explored the experiences of conducting clinical research during COVID-19 with clinical research stakeholders examining challenges faced and adaptations required. The findings inform, equip and support clinical research stakeholders in the event of future adverse public health events.

Differential Impact of Central Venous Catheters versus Arteriovenous Fistulae on Quality of Life among Irish Haemodialysis Patients.

Background: Arteriovenous fistulae (AVF) have superior clinical outcomes compared with central venous catheters (CVC) among patients undergoing hemodialysis (HD). Yet, there is increasing recognition that health-related quality of life (HRQoL) may be more important to patients than survival and that differences may exist between AVF and CVCs in this regard. This study compared HRQoL between AVF and CVC in an Irish cohort. Methods: We conducted a cross-sectional survey among prevalent patients undergoing hemodialysis (N=119) dialyzing with either an AVF or CVC at a regional program. The Short Form 36 (SF-36) and a validated Vascular Access Questionnaire (SF-VAQ) compared QoL between AVF and CVC in domains of physical functioning, social functioning, and dialysis complications. Multivariable logistic regression compared differences between groups for outcomes of physical functioning, social functioning, and dialysis complications expressed as adjusted odds ratios and 95% CI. Results: Mean age was 66.6 years; 52% were using an AVF and 48% had a CVC. Patients dialyzing with an AVF were more satisfied with their access when asked directly (6.2 versus 5.0; P<0.01). Physical functioning scores for bleeding, swelling, and bruising were significantly higher for AVF than CVC (P=0.001, P=0.001, and P<0.001, respectively). In contrast, patients with a CVC reported greater difficulties in bathing and showering than those using an AVF (4.4 versus 2.0; P<0.001), whereas patients with an AVF expressed greater concerns with physical appearances. Compared with AVF, CVC users were less likely to report difficulties in physical functioning (OR=0.35; 95% CI, 0.12 to 0.94; P=0.04) but more likely to report dialysis complications (OR=1.94; 95% CI, 0.69 to 5.87; P=0.22). Conclusions: Vascular access contributes to HRQoL in hemodialysis. CVCs are associated with fewer difficulties from bleeding and bruising but greater negative effect on social activities, including bathing and showering. Overall, patients with a CVC had lower dissatisfaction scores than patients with an AVF when all three domains were added. Innovation in vascular access design and engineering may confer benefits and improve patient comfort on HD.

A Feasibility and Acceptability Trial of Social Cognitive Therapy in Early Psychosis Delivered Through a Virtual World: The VEEP Study.

BACKGROUND: Addressing specific social cognitive difficulties is an important target in early psychosis and may help address poor functional outcomes. However, structured interventions using standard therapy settings including groups suffer from difficulties in recruitment and retention. AIMS: To address these issues, we aimed to modify an existing group social cognitive intervention entitled 'Social Cognition and Interaction Training' (SCIT) to be delivered through a virtual world environment (Second Life ©). METHODS: A single arm nonrandomized proof-of-concept trial of SCIT-VR was conducted. Five groups of three to five individuals per group were recruited over 6 months. Eight sessions of SCIT-VR therapy were delivered through the virtual world platform Second Life© over a 5-week intervention window. Feasibility was examined using recruitment rates and retention. Acceptability was examined using qualitative methods. Secondary outcomes including social cognitive indices, functioning, and anxiety were measured pre- and postintervention. RESULTS: The SCIT-VR therapy delivered was feasible (36% consent rate and 73.3% intervention completion rate), acceptable (high overall postsession satisfaction scores) and safe (no serious adverse events), and had high levels of participant satisfaction. Users found the environment immersive. Prepost changes were found in emotion recognition scores and levels of anxiety. There were no signs of clinical deterioration on any of the secondary measures. CONCLUSION: This proof-of-concept pilot trial suggested that delivering SCIT-VR through a virtual world is feasible and acceptable. There were some changes in prepost outcome measures that suggest the intervention has face validity. There is sufficient evidence to support a larger powered randomized controlled trial. CLINICAL TRIAL REGISTRATION: ISRCTN, identifier 41443166.

Improving specific autobiographical memory in older adults: impacts on mood, social problem solving, and functional limitations.

Older adults have difficulty recalling specific autobiographical events. This over-general memory style is a vulnerability factor for depression. Two groups receiving interventions that have previously been successful at reducing over-general memory in depressed populations were compared to a control group. Participants were healthy older adults aged ≥70 years: memory specificity training (MEST; n = 22), life review (n = 22), and control group (n = 22). There were significant improvements in autobiographical memory specificity in the MEST and life review groups at post-training, relative to the control group, suggesting that over-general memory can be reduced in older adults. Change in social problem solving ability and functional limitations were related to change in autobiographical memory specificity, supporting the suggested role of specific retrieval in generating solutions to social problems and maintaining independence. Qualitative analysis of participants' feedback revealed that life review may be more appropriate for older adults, possibly because it involves integrating specific memories into a positive narrative.

Demonstration of a hyperglycemia-driven pathogenic abnormality of copper homeostasis in diabetes and its reversibility by selective chelation: quantitative comparisons between the biology of copper and eight other nutritionally essential elements in normal and diabetic individuals.

We recently showed that treatment with the Cu(II)-selective chelator, trientine, alleviates heart failure in diabetic rats, improves left ventricular hypertrophy in humans with type 2 diabetes, and increases urinary Cu excretion in both diabetic rats and humans compared with nondiabetic control subjects. In this study, we characterized the homeostasis of Cu and eight other nutritionally essential elements in diabetes under fully residential conditions in male subjects with type 2 diabetes and age-matched control subjects. We then probed elemental balance with oral trientine in a parallel-group, placebo-controlled study in these subjects. Before treatment, there were no detectable between-group differences in the balance of any element, although urinary output of several elements was greater in diabetic subjects. Mean extracellular superoxide dismutase (EC-SOD) activity was elevated in diabetic subjects, and its activity correlated strongly with the interaction between [Cu]serum and HbA1c. Trientine caused the Cu balance to become negative in diabetic subjects through elevated urinary Cu losses and suppressed elevated EC-SOD. Basal urinary Cu predicted urinary Cu losses during treatment, which caused extraction of systemic Cu(II). We suggest that cardiovascular complications in diabetes might be better controlled by therapeutic strategies that focus on lowering plasma glucose and loosely bound systemic Cu(II).

Regeneration of the heart in diabetes by selective copper chelation.

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Although altered systemic regulation of transition metals in diabetes has been the subject of previous investigation, it is not known whether changed transition metal metabolism results in heart disease in common forms of diabetes and whether metal chelation can reverse the condition. We found that administration of the Cu-selective transition metal chelator trientine to rats with streptozotocin-induced diabetes caused increased urinary Cu excretion compared with matched controls. A Cu(II)-trientine complex was demonstrated in the urine of treated rats. In diabetic animals with established heart failure, we show here for the first time that 7 weeks of oral trientine therapy significantly alleviated heart failure without lowering blood glucose, substantially improved cardiomyocyte structure, and reversed elevations in left ventricular collagen and beta(1) integrin. Oral trientine treatment also caused elevated Cu excretion in humans with type 2 diabetes, in whom 6 months of treatment caused elevated left ventricular mass to decline significantly toward normal. These data implicate accumulation of elevated loosely bound Cu in the mechanism of cardiac damage in diabetes and support the use of selective Cu chelation in the treatment of this condition.

Measuring the cost, effectiveness, and cost-effectiveness of orthodontic care.

AIM: To determine the relative effectiveness and cost-effectiveness of orthodontic treatment per case in one "fee for item" and two different types of salaried orthodontic clinics. SUBJECTS AND METHODS: This prospective study recruited a random sample of six self-employed orthodontists (fee-for-item) and six orthodontists from both hospital and community clinics (salaried services). One hundred patients were followed to completion of orthodontic care. Questionnaires were employed to determine cost of treatment from the clinicians' and patients' points of views. Four cost-effectiveness models were developed. RESULTS: Complete records of outcome were available for 1,087 patients, but only 789 had complete data on costing. Three of the four cost-effectiveness models indicated similar rankings for the 18 clinicians. The most cost-effective service was provided by clinicians working in community clinics, followed by clinicians working in hospitals, then self-employed clinicians. The preferred cost-effective model takes into consideration the initial need and successful outcome of orthodontic treatment. CONCLUSION: Cost-effectiveness models have been developed to quantify the performance of individual clinicians working in self-employed and salaried clinics. Costs and effectiveness of the clinicians in each clinical setting show considerable variation.

Supplementation of a high-carbohydrate breakfast with barley beta-glucan improves postprandial glycaemic response for meals but not beverages.

There is growing support for the protective role of soluble fibre in type II diabetes. Soluble fibre beta-glucan found in cereal products including oats and barley may be the active component. There is evidence of postprandial blunting of blood glucose and insulin responses to dietary carbohydrates when oat soluble fibre is supplemented into the diet but few trials have been carried out using natural barley or enriched barley beta-glucan products. The aim of this trial was to investigate the postprandial effect of a highly enriched barley beta -glucan product on blood glucose, insulin and lipids when given with a high-CHO food and a high-CHO drink. 18 lean, healthy men completed a 4 treatment intervention trial comprising (i) high-CHO(food control), (ii) high-CHO(food+fibre), (iii) high-CHO(drink control), (iv) high-CHO(drink+fibre) where a 10g dose of barley beta-glucan fibre supplement (Cerogen) containing 6.31g beta-glucan was added to food and drink controls. There was an increase of glucose and insulin following all 4 treatments. Addition of the beta -glucan supplement significantly blunted the glycaemic and insulinaemic responses on the food (p<0.05) but not drink (p>0.05) treatments when compared to controls. The high-CHO breakfasts decreased total, LDL- and HDL-cholesterol from baseline to 60 mins postprandially but there were no differential effects of beta-glucan treatment on circulating lipids. We conclude that a high dose barley beta-glucan supplement can improve glucose control when added to a high-CHO starchy food, probably due to increased gastro-intestinal viscosity, but not when added to a high-CHO beverage where rapid absorption combined with decreased beta-glucan concentration and viscosity may obviate this mechanism.