Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.

Supplementary Table S1. Age and gender comparison between the current study and the UK incidence data (2002-2011); Supplementary Table S2. Comparison of age distribution in cases from 2002-2006 vs. 2007-2011; Supplementary Table S3. Type-specific HPV prevalence among single infected HPV-positive tumours

OBJECTIVE A new test method is described which provides a convenient technique for assessing the combined effects of gravity and compression on the fluid handling characteristics of surgical dressing which can have important implications for their use in the treatment of venous ulcers. Simple ways of improving use of the fluid handling capacity of products currently used clinically are suggested, and the possibility of developing a dressing specifically designed to resist gravitational effects is discussed.

INTRODUCTION:The management of exudate from leg ulcers remains a major challenge for health care practitioners. Many different dressings are available for this purpose, often used in conjunction with graduated external compression provided by extensible bandages applied in different configurations to achieve the required physiological effect. Although a significant amount of data has been published on the fluid-handling properties of some of these primary dressings, this has mainly been derived from laboratory studies using standard tests conducted in the horizontal plane, often without the addition of a secondary compression dressing.MATERIALS AND METHODS:A review of the literature failed to identify any publications which examined either the effects of compression bandages or gravity upon dressings tested in the vertical plane, simulating normal conditions of use. The present study was therefore undertaken to investigate the effect of both of these factors.RESULTS:While the application of multiple layers of bandages were found to have relatively little effect upon the loss of moisture vapor from a given dressing, compression and the effects of gravity were, in some instances, shown to significantly accelerate the rate of dressing failure, although important differences between products were noted in this regard.CONCLUSION:As a result of this work it is proposed that new test methods be devised which take account of both parameters to better inform potential users of the relative merits of various available dressing materials. .

OBJECTIVE:The present study was undertaken to demonstrate that the pressures produced by multiple layers of compression bandages applied to artificial limbs of known circumference with predetermined levels of tension can be predicted accurately using the modified Laplace equation. METHOD:Up to four layers of different bandage types were applied in a carefully controlled fashion to cylinders of known circumference, with tensions ranging from around 200-2000 grams/10cm width. The pressures generated were measured using pneumatic pressure sensors previously shown to possess the required degree of accuracy for this type of experimental system. RESULTS:Good correlation was observed between the mean and standard deviation of each pair of experimental and calculated pressure values for all combinations of bandage type, application tension and cylinder circumference. Over the clinically relevant range of pressures, the difference between data sets was generally less than 1.0mmHg. CONCLUSION:The results of this experimental study unequivocally prove that provided accurate values for all the relevant variables are known, it is possible to predict the pressure that will be developed by a compression bandage on a limb of known size. However, it is important to recognise that other factors such as the elastomeric properties of the fabric will have a major effect upon the ability of a bandage system to sustain initial compression values. Furthermore, the variation in radius of curvature around a limb will mean that point pressures readings recorded at individual locations around the circumference may vary dramatically from the average value predicted by the modified Laplace equation, calling into question the value of sub-bandage pressure measuring devices for this application.

OBJECTIVEThis study was undertaken to examine the accuracy of two hand-held devices commonly used to measure the pressures produced by extensible bandages.METHODThe performance of the pneumatic sensors of two devices, the Kikuhime and Picopress instruments was first examined in air in a compression chamber, then subsequently beneath multiple layers of bandages applied to standard cylinders with predetermined levels of tension.RESULTSIn the compression chamber, both instruments provided readings that were typically within 1 mmHg of the reference value, but on curved formers in free air or beneath bandages the accuracy of both sensors was greatly reduced, influenced both by the curvature of the cylinders and the volume of air contained in the sensor capsule. The Picopress instrument recorded pressures up to 70% higher than predicted, particularly on the smaller cylinders and at the lower end of the pressure range (circa 20mmHg). At 40mmHg measured pressure were around 40% higher than predicted values in some instances. The accuracy of the Kikuhime was greatly influenced by the calibration technique but percentage deviations as high as 150% were recorded in some tests.CONCLUSIONPneumatic pressure sensors used to record the pressures developed beneath compression bandages are much less accurate than is commonly believed. Calibration studies using air chambers or water tanks have no relevance to the normal clinical use of these devices. These limitations should be considered by clinicians when making judgments about the performance of other medical devices such as bandages or stockings. They also call into question the validity of many published studies which rely upon such measurements.DECLARATION OF INTERESTThis project was generously supported by 3M Healthcare who provided a small research grant to assist with the costs associated with the construction of the test equipment.

Despite the fact that, globally, surgical dressings are used under very different environmental conditions, most wound care professionals are unaware of the effects of varying temperature and relative humidity on certain key aspects of dressing performance. In particular, both these parameters can have a marked effect upon the moisture vapor transmission rate of dressings which incorporate a semipermeable film or membrane within their structure. This paper describes the use of an online calculator, the development of which has been described previously, to illustrate for the first time how changes in the weather might affect the ability of a dressing to cope with the exudate produced by an exuding wound. The results suggest that, under certain conditions, dressing permeability may fall to about 30% of experimentally determined values with potentially important consequences for wear times and treatment costs.

The moisture vapour permeability of a dressing can make an important contribution to its overall fluid handling capacity. Despite the fact that this parameter is often quoted in scientific literature and manufacturers' promotional material, it is a concept that is not generally well understood. In particular, the effect of changing environmental conditions upon experimentally determined permeability values for particular dressings is rarely acknowledged. The present study was undertaken to derive and validate a method that could be used to predict the permeability of a self-adhesive semipermeable film dressing under specific conditions of temperature and humidity using a single set of data generated in the laboratory. A calculator that facilitates this process is also described.

OBJECTIVETo compare the fluid-handling properties of a range of commonly used absorbent foam dressings. Results were analysed to generate broad estimates of wear time, using previously published data for the rate at which exudate is produced by various wound types.METHODTest data were produced by an independent, accredited test facility using a series of standard test systems, and submitted to the author for review and interpretation.RESULTSAbsorbency values for the cavity foam dressings tested ranged from 11 to 16 grams per 10cm(2) sample under the specified test conditions. The increase in dressing volume ranged from 71% to 206%, although this did not always correlate directly with absorbency values. Foam-film dressing tests revealed large variations in product performance. The total fluid handling capacity of dressings (the sum of absorbency and evaporative loss) ranged from approximately 7 to 26 grams per sample. These differences are largely due to variations in permeability of the film backing layer, which ranged from approximately 2000 to 20,000g/m(2)/24h. Compression reduced the absorbency of most dressings but it appeared to enhance the performance of one product (possibly through ensuring contact between the test sample and the simulated wound bed). 9 of the 11 sheet dressings tested were estimated to be capable of managing normal levels of wound exudate for 48 hours, based solely on their absorbency figures. Considering the additional effects of moisture vapour permeability, theoretical wear time increases to five days in a number of instances.CONCLUSIONThe laboratory data suggest considerable differences in the clinical performance of dressings. Making a number of assumptions as stated in the text, predicted values for clinical performance were generated. These estimates show marked differences between dressings.DECLARATION OF INTERESTThis report was produced by the author for a professional fee, from BSN, as a medical device consultant and medical writer using test data generated independently by an accredited laboratory. The author had no involvement either with the choice of test methods, or the range of dressings included in the study, and has no financial interests in any of the products concerned.

In 1766, a French physician proposed a protocol of care for patients with leg ulcers that anticipates much modern thinking on this topic. So, has our understanding increased as much as we think or is there still much to learn and do?

In 1766, a French physician wrote a treatise on wound management. Despite the lack of knowledge on physiology of wound healing and causes of infection, much of the clinical advice given in the text still holds true today

Almost paper thin, this new dressing is sufficiently permeable to cope with moderately exuding wounds, such as burns and donor sites. This review assesses the existing laboratory and clinical data on this novel dressing type.

OBJECTIVE:To investigate the fluid-handling mechanisms of film-backed foam dressings.METHOD:The fluid-handling properties of two dressings (ActivHeal Foam Island, Advanced Medical Solutions, and Allevyn Adhesive, Smith & Nephew) were compared using a standard laboratory technique, which provided comparative data on the dressings' absorbency and moisture vapour transmission. Movement of exudate through one of the dressings was also investigated in vivo using ultrasound. The fluid-handling data obtained in the laboratory were compared with exudate rates for various wound types reported in the literature to predict wear times for above products.RESULTS:Absorbencies of the two dressings were broadly comparable. After 24 hours, under the test conditions, ActivHeal retained a mean of 3.44 g (SD 0.04) of the test solution and Allevyn Adhesive 4.32 g (SD 0.04), but a major difference was detected in the permeability of the two products: 12.35 g (SD 0.42) of the test solution evaporated through the back of Allevyn over 24 hours compared with 1.67 g (SD 0.11) through ActivHeal (p<0.0001). The results of the preliminary ultrasound study suggest that, in the clinical situation, exudate migrates away from the wound surface and accumulates beneath the outer film.CONCLUSION:The difference in fluid-handling properties of the two dressings was due to the presence in one of an 'intelligent' polyurethane film component, the permeability of which varied in response to the presence of liquid. The data suggested that the film's permeability was such that the product might be expected to cope with even the most heavily exuding wounds for an extended period, but this performance would be influenced in vivo by factors such as the size of the dressing relative to the wound, and local environmental conditions, which would affect moisture vapour transmission. The somewhat unexpected finding that fluid tended to accumulate beneath the outer film during clinical use suggested the possibility of an 'osmotic pump' effect.

A review of the literature suggests that the application of self-adhesive hydrocolloid dressings, most commonly associated with the treatment of ulcerative conditions such as pressure ulcers and leg ulcers, may also offer benefits in the management of acute wounds of all types, for example decreasing healing times of donor sites by about 40% compared with traditional treatments. Healing times of superficial traumatic injuries and surgical wounds are similarly enhanced but in the treatment of burns, the principal benefit appears to be a reduction in wound pain, an effect that has also been reported in virtually all other wound types. The impermeable nature of hydrocolloids provides a protective covering to the wound, permitting washing or showering while helping to prevent the spread of pathogenic microorganisms. There also appear to be significant cost-benefits associated with the use of hydrocolloids. In recent years, hydrocolloid dressings have been replaced by other products such as foams for the treatment of more heavily exuding wounds but for more lightly exuding wounds they still offer many practical advantages and as such will undoubtedly continue to meet an important need in wound management practice.

The importance of debridement in wound healing is well established. This review calculates the cost savings that might be achieved when using maggot debridement therapy on chronic wounds instead of autolytic debridement.

The root causes of health disparities are numerous and relate to individual behaviors, provider knowledge and attitudes, organization of the health care system, and societal and cultural values. Disparities have been well documented,even in systems that provide unencumbered access to health care, such as the VA Healthcare System, suggesting that factors other than access to care (e.g., culture and health communication) are responsible. Efforts to eliminate health disparities must be informed by the influence of culture on the attitudes, beliefs, and practices of not only minority populations but also public health policymakers and the health professionals responsible for the delivery of medical services and public health interventions designed to close the health gap. There is credible evidence suggesting that cultural norms within Western societies contribute to lifestyles and behaviors associated with risk factors for chronic diseases (e.g., diabetes and cardiovascular disease). This is the context in which smoking cessation, increased physical activity, and dietary regulation are prime targets for intervention.