Identification of immune and non-immune cells in regenerating axolotl limbs by single-cell sequencing.

Immune cells are known to be critical for successful limb regeneration in the axolotl (Ambystoma mexicanum), but many details regarding their identity, behavior, and function are yet to be resolved. We isolated peripheral leukocytes from the blood of adult axolotls and then created two samples for single-cell sequencing: 1) peripheral leukocytes (N = 7889) and 2) peripheral leukocytes with presumptive macrophages from the intraperitoneal cavity (N = 4998). Using k-means clustering, we identified 6 cell populations from each sample that presented gene expression patterns indicative of erythrocyte, thrombocyte, neutrophil, B-cell, T-cell, and myeloid cell populations. A seventh, presumptive macrophage cell population was identified uniquely from sample 2. We then isolated cells from amputated axolotl limbs at 1 and 6 days post-amputation (DPA) and performed single cell sequencing (N = 8272 and 9906 cells respectively) to identify immune and non-immune cell populations. Using k-means clustering, we identified 8 cell populations overall, with the majority of cells expressing erythrocyte-specific genes. Even though erythrocytes predominated, we used an unbiased approach to identify infiltrating neutrophil, macrophage, and lymphocyte populations at both time points. Additionally, populations expressing genes for epidermal cells, fibroblast-like cells, and endothelial cells were also identified. Consistent with results from previous experimental studies, neutrophils were more abundant at 1 DPA than 6 DPA, while macrophages and non-immune cells exhibited inverse abundance patterns. Of note, we identified a small population of fibroblast-like cells at 1 DPA that was represented by considerably more cells at 6 DPA. We hypothesize that these are early progenitor cells that give rise to the blastema. The enriched gene sets from our work will aid future single-cell investigations of immune cell diversity and function during axolotl limb regeneration.

A multicentre, clinical evaluation of a hydro-responsive wound dressing: the Glasgow experience.

OBJECTIVE: Our aim was to assess the effectiveness of hydro-responsive wound dressing (HRWD) in debridement and wound bed preparation of a variety of acute and chronic wounds that presented with devitalised tissue needing removal so that healing may proceed. METHOD: This was a non-comparative evaluation of acute and chronic wounds that required debridement as part of their normal treatment regimen. Clinicians recorded wound changes including a subjective assessment level of devitalised tissue and wound bed preparation, presence of pain, wound status (e.g., wound size) and periwound skin condition. Data was also collected from clinicians and patients to provide information on clinical performance of the dressing. RESULTS: We recruited 100 patients with a variety of wound types into the study. Over 90% of the clinicians reported removal of devitalised tissue to enable a healing response in both chronic and acute wounds. Specifically, over the course of the evaluation period, levels of devitalised tissue (necrosis and slough) reduced from 85.5% to 26.3%, and this was accompanied by an increase in wound bed granulation from 12.0% to 33.7%. Correspondingly, there was a 40% reduction in wound area, hence a clinically relevant healing response was seen upon treatment with HRWD. It is also noteworthy that this patient population included a significant proportion of chronic wounds (51.4%) that showed no signs of wound progression within <4 weeks before study inclusion. Of these chronic wounds, 93% demonstrated wound progression upon treatment with HRWD. Despite reported pain levels being low pre- and post-dressing change, overall wound pain improved (reduced) in 48% of patients. Periwound skin condition showed a tendency towards improvement, and the fluid management capabilities of the HRWD was reported as good to excellent in the majority of cases. Wound infections were reduced by at least 60% over the evaluation period. A simple cost-effective analysis demonstrated significant savings using HRWD (£6.33) over current standard practice regimens of a four-step debridement process (£8.05), larval therapy (£306.39) and mechanical pad debridement (£11.46). CONCLUSION: HRWD was well tolerated and was demonstrated to be an efficient debridement tool providing rapid, effective and pain free debridement in a variety of wound types.

Woodland caribou calving fidelity: Spatial location, habitat, or both?

Individuals that isolate themselves to give birth can use more than one strategy in choosing birth sites to maximize reproductive success. Previous research has focused on the consistency in the use of the same birth-site across years (i.e., spatial fidelity), but individuals alternatively may use similar habitat conditions across years (i.e., habitat fidelity). Using GPS telemetry, we determined whether woodland caribou expressed spatial or habitat fidelity during calving, and evaluated intrinsic and extrinsic factors associated with expressing either type of fidelity. We identified 56 individuals with ≥2 putative birth events, via a movement-based model, across northern Ontario between 2010 and 2014. Individuals were classified as expressing (1) spatial fidelity by comparing sequential calving locations to a random spatial distribution of available calving locations, (2) habitat fidelity using a logistic use model compared to a null (intercept only) model, (3) no fidelity (neither criterion met), or (4) both spatial and habitat fidelity (both criteria met). Across all individuals, 37% expressed no fidelity (36 of 98), 15% expressed only spatial fidelity (15 of 99), 35% expressed only habitat fidelity (34 of 98), and 14% expressed both spatial and habitat fidelity (14 of 98). Older individuals were more likely to express spatial fidelity, whereas lower availability of upland and lowland conifer forests without linear features increased the probability an individual expressed habitat fidelity. Our results indicate that managing for caribou calving needs to consider protecting both specific, known birthing sites, but also broad-scale areas of preferred habitat for calving. Understanding the mechanisms that influence caribou expressing calving fidelity, and associated fitness costs, is crucial for the conservation of the species.

Optimisation of hepatocellular carcinoma surveillance in patients with viral hepatitis: a quality improvement study.

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasound is a standard of care for higher-risk patients with viral hepatitis. Adherence to screening guidelines is an important quality indicator in hepatology, but multiple studies have demonstrated poor HCC surveillance practices in real-world settings. AIMS: The aim of this project was to audit and then optimise HCC surveillance of viral hepatitis patients, who fulfilled criteria for screening, associated with a large tertiary hospital. METHODS: Clinical practice improvement principles were utilised. A baseline audit of 22 consecutive viral hepatitis patients was performed. Major barriers preventing adequate surveillance were identified and three interventions to improve adherence to guidelines were introduced. These included: improved doctor education, system redesign and improved patient education. The effects of interventions were measured by serial random audits of patients. A final audit occurred over 3 years after the initial baseline audit. RESULTS: At baseline, 46% and 0% of patients had appropriate surveillance performed during the prior 6 months (one surveillance cycle) and 2 years (four surveillance cycles) respectively. Three years after initiation of these strategies, a final audit revealed 92% (vs 46% at baseline) and 64% (vs 0% at baseline) of patients had appropriate HCC surveillance performed during the preceding 6 months and 2 years intervals respectively (P < 0.001 in each case). CONCLUSIONS: Simple and low-cost interventions can considerably improve the clinical effectiveness of HCC screening programmes in real world settings. Clinical practice improvement principles appear to be a valid methodology for achieving this positive change.

Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: An association between resting heart rate and mortality has been described in the general population and in patients with cardiovascular disease. There are, however, few data exploring this relationship in patients with type 2 diabetes mellitus. The current study addresses this issue. METHODS: The relationship between baseline resting heart rate and all-cause mortality, cardiovascular death and major cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) was examined in 11,140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study. RESULTS: A higher resting heart rate was associated with a significantly increased risk of all-cause mortality (fully adjusted HR 1.15 per 10 bpm [95% CI 1.08, 1.21], p<0.001), cardiovascular death and major cardiovascular outcomes without adjustment and after adjusting for age and sex and multiple covariates. The increased risk associated with a higher baseline resting heart rate was most obvious in patients with previous macrovascular complications (fully adjusted HR for death 1.79 for upper [mean 91 bpm] vs lowest [mean 58 bpm] fifth of resting heart rate in this subgroup [95% CI 1.28, 2.50], p = .001). CONCLUSIONS/INTERPRETATION: Among patients with type 2 diabetes, a higher resting heart rate is associated with an increased risk of death and cardiovascular complications. It remains unclear whether a higher heart rate directly mediates the increased risk or is a marker for other factors that determine a poor outcome.

Diversity of faecal oxalate-degrading bacteria in black and white South African study groups: insights into understanding the rarity of urolithiasis in the black group.

AIM: To examine whether enhanced diversity or numbers of oxalate-degrading bacteria in the gastrointestinal tracts of black South Africans play a role in determining the rarity of urolithiasis in this group. METHODS AND RESULTS: Fresh faecal samples collected from healthy black and white South African male volunteers were analysed in terms of bacterial oxalate-degrading activity, bacterial diversity and relative species abundance. Varied bacterial populations prepared from samples from the low-risk black group showed a significantly higher level of oxalate degradation. Denaturing gradient gel electrophoresis analyses of Lactobacillus and related spp. and Bifidobacterium spp. 16S rRNA PCR products revealed a significantly higher faecal Lactobacillus diversity for the low-risk black group relative to the higher-risk white group. Quantitative real-time PCR experiments did not show any significant differences between the study groups for Lactobacillus and related spp.. However, Bifidobacterium spp. were present at a significantly higher relative abundance in the black group. Oxalobacter formigenes was present only at very low levels in either group. CONCLUSIONS: The low abundance of O. formigenes and increased diversity and abundance of oxalate-degrading Lactobacillus and Bifidobacterium spp. in the black South African population suggest that these strains rather than O. formigenes may protect this group against calcium oxalate kidney stone disease. SIGNIFICANCE AND IMPACT OF THE STUDY: The South African black population harbours a pool of potential oxalate-degrading lactic acid bacteria, which is more abundant and diverse than that of white South Africans. This may be useful in developing probiotics for calcium oxalate kidney stone prophylaxis.

Single centre experience with pegylated interferon and ribavirin for hepatitis C: looking back before moving forward.

BACKGROUND: Hepatitis C treatment is successful in 40-80% of patients in drug sponsored registration trials. However, few studies have examined treatment outcomes in non-trial, routine clinical practice settings. AIM: The aim of this study was to investigate the treatment outcomes and predictors of a sustained virological response in a routine clinical setting. METHODS: Data were collected retrospectively on patients treated for hepatitis C between January 2004 and March 2010 in a tertiary hospital setting. Demographics, treatment outcomes and potential predictors of outcome (viral genotype, viral load, virological response, platelet count, alanine transaminase level, glucose, ferritin, weight, fibrosis and cirrhosis, compliance, dose reductions, adverse events, psychiatric and alcohol history) were recorded. Univariate and multiple logistic regressions were performed. RESULTS: A total of 405 patients was treated during the study period. On an intention to treat basis, sustained virological response rates were 55%, 82% and 72% in genotypes 1, 2 and 3 respectively. Predictors of response were gender, age, genotype, weight, fibrosis, cirrhosis, platelet count and alanine transaminase on univariate analysis. Age, genotype, cirrhosis and platelet count were independently associated with sustained virological response on multiple logistic regression. CONCLUSION: In our cohort, treatment outcomes for genotype 1 and 2 were similar to results from clinical trials but results for genotype 3 were inferior. Clinicians should not assume that results from registration trials are transferable to their own clinical practice. This has particular relevance for the new era of triple therapy regimens containing direct antivirals.

Protection in simian immunodeficiency virus-vaccinated monkeys correlates with anti-HLA class I antibody response.

Our earlier reports demonstrated that Cynomolgus macaques vaccinated with either inactivated partially purified simian immunodeficiency virus (SIV), fixed SIV-infected C8166 (a human T lymphoblastoid cell line) cells, or fixed uninfected C8166 cells can be protected against a challenge infection with the 32H isolate of SIVmac 251 (grown in C8166) (Stott, E. J., W. L. Chan, K. H. G. Mills, M. Page, F. Taffs, M. Cranage, P. Greenway, and P. Kitchin. 1990. Lancet. 336:1538; Stott, E. J., P. A. Kitchin, M. Page, B. Flanagan, L. F. Taffs, W. L. Chan, K. H. G. Mills, P. Silvera, and A. Rodgers. 1991. Nature [Lond.]. 353:393). Protection is correlated with the levels of antibody response to cellular antigens in the human cells from which the virus immunogen was grown. However, the mechanism of protection is unclear. We report here the analysis of sera from these protected monkeys and demonstrate that there is positive correlation of protection with antibody response to the HLA class I molecule.

Use of electronic sales data to tailor nutrition education resources for an ethnically diverse population.

BACKGROUND: Nutrition education may be most effective when personally tailored. Individualised electronic supermarket sales data offer opportunities to tailor nutrition education using shopper's usual food purchases. The present study aimed to use individualised electronic supermarket sales data to tailor nutrition resources for an ethnically diverse population in a large supermarket intervention trial in New Zealand. METHODS: Culturally appropriate nutrition education resources (i.e. messages and shopping lists) were developed with the target population (through two sets of focus groups) and ethnic researchers. A nutrient database of supermarket products was developed using retrospective sales data and linked to participant sales to allow tailoring by usual food purchases. Modified Heart Foundation Tick criteria were used to identify 'healthier' products in the database suitable for promotion in the resources. Rules were developed to create a monthly report listing the tailored and culturally targeted messages to be sent to each participant, and to produce automated, tailored shopping lists. RESULTS: Culturally targeted nutrition messages (n = 864) and shopping lists (n = 3 formats) were developed. The food and nutrient database (n = 3000 top-selling products) was created using 12 months of retrospective sales data, and comprised 60%'healthier' products. Three months of baseline sales data were used to determine usual food purchases. Tailored resources were successfully mailed to 123 Maori, 52 Pacific and 346 non-Maori non-Pacific participants over the 6-month trial intervention period. CONCLUSIONS: Electronic supermarket sales data can be used to tailor nutrition education resources for a large number of ethnically diverse supermarket shoppers.

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans.

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.

Age effects on placebo response rates in clinical trials of acute agents for migraine: pooled analysis of rizatriptan trials in adults.

This study examined the effect of age on placebo response rates in rizatriptan trials in adults. Data from eight rizatriptan adult trials involving patients treating moderate/severe migraine attacks with rizatriptan 5 mg (N = 1819), rizatriptan 10 mg (N = 2046) or placebo (N = 1322) were pooled for post hoc analysis. Logistic regression was used to model 2-h pain relief (reduction to mild or none) and 2-h pain freedom rates by treatment groups. Older patients had lower placebo response rates than younger patients; the estimated odds ratio (older vs. younger) for a 10-year age increase was 0.83 for pain relief [95% confidence interval (CI) 0.75, 0.93] and 0.81 for pain freedom (95% CI 0.68, 0.97). The response proportion vs. age trend was flat for rizatriptan 5 mg and slightly increased for rizatriptan 10 mg. The treatment-by-age interaction was significant for pain relief (P < 0.001) and pain freedom (P = 0.001), suggesting an increasing trend of treatment advantage of rizatriptan over placebo as age increased. Age appeared to be an important predictor of placebo response rate in rizatriptan trials, with older patients being less likely to respond to placebo and more likely to respond to rizatriptan.

Calciuria, oxaluria and phosphaturia after ingestion of glucose, xylitol and sorbitol in two population groups with different stone-risk profiles.

The effects of glucose, sorbitol and xylitol ingestion on calciuria, oxaluria and phosphaturia in healthy black and white males on a standardized diet were investigated. After ingestion, they collected urine hourly for 3 h. Glucose decreased phosphaturia in blacks. Sorbitol decreased phosphaturia in both groups and increased oxaluria in whites. Xylitol increased oxaluria in blacks. Decreases in phosphaturia are attributed to penetration by phosphate into cells leading to decreases in phosphatemia and the renal filtered load. We suggest that this mechanism is more sensitive in blacks. We speculate that the increase in oxaluria after sorbitol ingestion occurs via its conversion to glyoxylate and that this pathway may be blocked in blacks. For the increase in oxaluria after xylitol ingestion, it is hypothesized that ketohexokinase and aldolase may be more active in blacks. Our results demonstrate, for the first time, a urinary effect due to sorbitol ingestion and an ethnic dependency of these and other effects.

Txt2stop: a pilot randomised controlled trial of mobile phone-based smoking cessation support.

AIM: To conduct a pilot randomised controlled trial of mobile phone-based smoking cessation support intervention for the UK population. DESIGN: Randomised controlled trial (txt2stop). SETTING: Community. PARTICIPANTS: 200 participants responding to radio, poster and leaflet-based promotions regarding the trial. MAIN OUTCOME MEASURES: The response rate for the outcome measures planned for the main trial. Participants' qualitative responses to open-ended questions about the intervention content. Secondary outcomes were the outcomes planned for the main trial including the point prevalence of self-reported smoking at 4 weeks and pooled effect estimate for the short-term results for the STOMP and txt2stop trials. RESULTS: The response rate at 4 weeks was 96% and at 6 months was 92%. The results at 4 weeks show a doubling of self-reported quitting relative risk (RR) 2.08 (95% CI 1.11 to 3.89), 26% vs 12%. The pooled effect estimate combining txt2stop and a previous New Zealand trial in the short term is RR 2.18 (95% CI 1.79 to 2.65). CONCLUSIONS: Mobile phone-based smoking cessation is an innovative means of delivering smoking cessation support, which doubles the self-reported quit rate in the short term. It could represent an important, but as yet largely unused, medium to deliver age-appropriate public health measures. The long-term effect of this mobile phone-based smoking cessation support will be established by a large randomised controlled trial currently in recruitment.

Cytomegalovirus colitis: an unusual cause of diarrhoea in the immunocompetent.

Cytomegalovirus (CMV) colitis is rarely reported in the immuno-competent adult and is often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). An index of suspicion in the appropriate setting is vital to diagnosing the condition. Undiagnosed CMV colitis has a significant morbidity. A review of the natural history and diagnosis of CMV is followed by a discussion of the incidence, outcome and possible treatment of CMV in the immunocompetent patient. The possible association between CMV and IBD is also reviewed, and the question of whether this should have any bearing on treatment is discussed at some length.

Vision for the future on urolithiasis: research, management, education and training-some personal views.

The field of urolithiasis has undergone many rapid changes in the last 3 decades. In this article, three eminent experts in various fields of urolithiasis research describe their respective visions for the future in stone research, stone treatment and surgical training. Many stone researchers have seen and regretted that there has not been a real breakthrough for decades now. Exceptions are the application of citrate prophylaxis and the abandonment of calcium-avoiding diet in stone formers. Certain areas of stone research have been exhausted and the body of literature available should suffice as background knowledge in those. Yet, to find meaningful mechanisms of clinically applicable stone prevention, the limited funds which are currently available should be used to research priority areas, of which crystal-cell interaction is envisioned by one of the present authors as being a crucial direction in future stone research. In the opinion of the second author, surgical stone treatment is very much technology-driven. This applies to the evolution of existing technologies and instruments. In addition, robotics, IT and communication software, and artificial intelligence are promising and are steadily making a meaningful impact in medicine in general, and endourology in particular. Finally, the third author believes that despite the exciting advances in technology, the role of the surgeon can never be replaced. The idea of a fully automated, artificially thinking and robotically performing system treating patients medically and surgically will not appeal to urologists or patients but may at least be a partial reality. His vision therefore is that surgical training will have to take on a new dimension, away from the patient and towards virtual reality, until the skill set is acceptably developed.

HDAC Regulates Transcription at the Outset of Axolotl Tail Regeneration.

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited regeneration through the first 7 days, however after this time, regeneration commenced with variable outgrowth of tailfin tissue and abnormal patterning. Microarray analysis showed that romidepsin altered early, transcriptional responses at 3 and 6-hour post-amputation, especially targeting genes that are implicated in tumor cell death, as well as genes that function in the regulation of transcription, cell differentiation, cell proliferation, pattern specification, and tissue morphogenesis. Our results show that HDAC activity is required at the time of tail amputation to regulate the initial transcriptional response to injury and regeneration.

Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial.

BACKGROUND: Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the effects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs. METHODS: The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925. FINDINGS: After a mean of 4.3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00, p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant (macrovascular 0.92; 0.81-1.04, p=0.16; microvascular 0.91; 0.80-1.04, p=0.16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3.8%] active vs 257 [4.6%] placebo; 0.82, 0.68-0.98, p=0.03) and death from any cause was reduced by 14% (408 [7.3%] active vs 471 [8.5%] placebo; 0.86, 0.75-0.98, p=0.03). There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline. INTERPRETATION: Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confidence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy.

Randomized clinical trial of honey-impregnated dressings for venous leg ulcers.

BACKGROUND: The efficacy of honey as a treatment for venous ulcers has not been evaluated, despite widespread interest. This trial aimed to evaluate the safety and effectiveness of honey as a dressing for venous ulcers. METHODS: This community-based open-label randomized trial allocated people with a venous ulcer to calcium alginate dressings impregnated with manuka honey or usual care. All participants received compression bandaging. The primary outcome was the proportion of ulcers healed after 12 weeks. Secondary outcomes were: time to healing, change in ulcer area, incidence of infection, costs per healed ulcer, adverse events and quality of life. Analysis was by intention to treat. RESULTS: Of 368 participants, 187 were randomized to honey and 181 to usual care. At 12 weeks, 104 ulcers (55.6 per cent) in the honey-treated group and 90 (49.7 per cent) in the usual care group had healed (absolute increase 5.9 (95 per cent confidence interval (c.i.) -4.3 to 15.7) per cent; P = 0.258). Treatment with honey was probably more expensive and associated with more adverse events (relative risk 1.3 (95 per cent c.i. 1.1 to 1.6); P = 0.013). There were no significant differences between the groups for other outcomes. CONCLUSION: Honey-impregnated dressings did not significantly improve venous ulcer healing at 12 weeks compared with usual care. REGISTRATION NUMBER: ISRCTN 06161544 (http://www.controlled-trials.com).

Investigations of trace and toxic elements of kidney stones from two different Sudanese areas by µ-PIXE using Nuclear Microprobe (NMP).

In this study 14 kidney stones (oxalate and phosphate stones) collected from two Sudanese hospitals Particle Induced X ray Emission (µ-PIXE). This technique was used to investigate the matrix as well as the trace element compositions of kidney stones on a microscopic scale using 1.5MeV proton energy. Significant differences in elements content across the groups were found by applying statistical methods. Trace elements such as P,Ca, Fe, Ni, Cu, Zn, Se, Sr, Br, and Pb showed a possible linear relationship of the mean profile for trace elements for each group of stones. This study shows that micro analysis of urinary stones can provide complementary information on patients' exposure to epidemiological risk factors such as geography, diet and drinking water.