A digital assessment and documentation tool evaluated for daily podiatric wound practice.

INTRODUCTION: Foot ulcers are a common complication of diabetes. Regular screening of patients with ulcers enables better treatment and reduces the number of amputations. The lack of wound specialists, especially in nonurban areas, drove the development of an IT-based system for analyzing wounds, the Wound Healing Analyzing Tool (WHAT). Digital images are scored and documented using software that runs on a laptop computer. The aim of this study was to evaluate WHAT's use in daily podiatry practice. METHODS: Eighteen ambulant patients presenting with diabetic foot ulcers at the participating podiatric clinic were recruited to the study. Digital ulcer images were obtained. To measure size and assess wound bed condition, the evaluated software recognizes the square mark, which is printed on a sticker and placed next to the ulcer. A trained, blinded physician assessed the same digital images and results were compared. RESULTS: Fifteen of the 18 results obtained with the digital tool for ulcer area and wound bed condition were in line with the visual assessment conducted by the blinded physician. Eighty-seven percent of the images were correctly scored, with the main problem being a missing or partially visible square mark in the photograph (n = 3/18). CONCLUSION: The results indicate that WHAT showed sufficient accuracy to be considered for use in clinical settings for determination of wound area and wound bed characteristics. The tool also seems to be an attractive option for digital consulting.

The Spatial-Temporal Dimension of Oncological Prevalence and Mortality in Romania.

The objective of this study was to identify spatial disparities in the distribution of cancer hotspots within Romania. Additionally, the research aimed to track prevailing trends in cancer prevalence and mortality according to a cancer type. The study covered the timeframe between 2008 and 2017, examining all 3,181 territorial administrative units. The analysis of spatial distribution relied on two key parameters. The first parameter, persistence, measured the duration for which cancer prevalence exceeded the 75th percentile threshold. Cancer prevalence refers to the total number of individuals in a population who have been diagnosed with cancer at a specific time point, including both newly diagnosed cases (occurrence) and existing cases. The second parameter, the time continuity of persistence, calculated the consecutive months during which cancer prevalence consistently surpassed the 75th percentile threshold. Notably, persistence of elevated values was also evident in lowland regions, devoid of any discernible direct connection to environmental conditions. In conclusion, this work bears substantial relevance to regional health policies, by aiding in the formulation of prevention strategies, while also fostering a deeper comprehension of the socioeconomic and environmental factors contributing to cancer.

A Framework for Determining the Performance and Requirements of Cable-Driven Mobile Lower Limb Rehabilitation Exoskeletons.

The global increase in the number of stroke patients and limited accessibility to rehabilitation has promoted an increase in the design and development of mobile exoskeletons. Robot-assisted mobile rehabilitation is rapidly emerging as a viable tool as it could provide intensive repetitive movement training and timely standardized delivery of therapy as compared to conventional manual therapy. However, the majority of existing lower limb exoskeletons continue to be heavy and induce unnecessary inertia and inertial vibration on the limb. Cable-driven exoskeletons can overcome these issues with the provision of remote actuation. However, the number of cables and routing can be selected in various ways posing a challenge to designers regarding the optimal design configuration. In this work, a simulation-based generalized framework for modelling and assessment of cable-driven mobile exoskeleton is proposed. The framework can be implemented to identify a 'suitable' configuration from several potential ones or to identify the optimal routing parameters for a given configuration. For a proof of concept, four conceptual configurations of cable-driven exoskeletons (one with a spring) were developed in a manner where both positive and negative moments could be generated for each joint (antagonistic configuration). The models were analyzed using the proposed framework and a decision metric table has been developed based on the models' performance and requirements. The weight of the metrics can be adjusted depending on the preferences and specified constraints. The maximum score is assigned to the configuration with minimum requirement or error, maximum performance, and vice versa. The metric table indicated that the 4-cable configuration is a promising design option for a lower limb rehabilitation exoskeleton based on tracking performance, model requirements, and component forces exerted on the limb.

Vitamin E supplementation during the dry period in dairy cattle. Part II: oxidative stress following vitamin E supplementation may increase clinical mastitis incidence postpartum.

The aim of this study was to evaluate, retrospectively, which physiological states influenced the effect of vitamin E supplements during the dry period on the level of oxidative stress at 2 wk antepartum. Furthermore the effect of oxidative stress at 2 wk antepartum on the risk of clinical mastitis in early lactation was investigated. Cows experience oxidative stress around calving. Vitamin E is able to decrease oxidative stress by scavenging free radicals. Normally, vitamin E radicals formed when vitamin E reacts with free radicals are regenerated by a network of other antioxidants, termed the "vitamin E regeneration system" (VERS). In case of vitamin E supplementation, VERS should be sufficient to regenerate formed vitamin E radicals; if not, oxidative stress might increase instead of decrease. Additionally, the level of oxidative stress and vitamin E might be important physiological states to evaluate before supplementation. In a clinical trial, 296 cows on 5 farms were randomly divided into 2 groups, supplemented with a mineral mix between dry off and calving that supplied 3,000 or 135 IU/d, respectively. Blood samples collected at dry off and 2 wk antepartum were analyzed for vitamin E, reactive oxygen metabolites, ferric-reducing ability of plasma, glutathione peroxidase, and malondialdehyde. Cows were allocated retrospectively into 8 subgroups based on the level of oxidative stress, vitamin E, and VERS status at dry off. To evaluate whether differences in physiological states at dry off influenced the effect of vitamin E supplementation on the level of oxidative stress, group effects (supplemented vs. control) were studied with Student's t-test for all 8 subgroup at 2 wk antepartum. Differences in physiological states at dry off influenced the effect of vitamin E supplements. In 2 insufficient VERS subgroups, the supplemented group had higher levels of free radicals at 2 wk antepartum compared with the control group. Relative risk calculation was used to study the effect of oxidative stress at 2 wk antepartum on the incidence of mastitis in the first 100 d of lactation. Higher levels of oxidative stress at 2 wk antepartum were related to higher risk of clinical mastitis. In conclusion, not every dry cow responded well to high vitamin E supplementation. This subgroup analysis provides a possible explanation for the unexpected adverse effects observed in the clinical trial.

Assessment of diabetic macrovascular complications: a prediabetes model.

Prediabetes is a condition that requires early intervention against diabetic macrovascular complications. This study aims to assess whether or not the likelihood of diabetes macrovascular complications occurring in prediabetes can be better estimated by a model combining a set of conventional and emerging biomarkers, with a view to improving cardiovascular disease (CVD) screening in individuals with elevated blood glucose levels associated with prediabetes. A total of 71 participants (female/male: 32/39) were divided into two groups - the prediabetic group (preDM: n=34) and the diabetic with cardiovascular complications group (DM+CVD: n=37). Blood glucose level (BGL), blood pressure (BP), total cholesterol (TC), high-density lipoprotein (HDL) and TC:HDL ratio, erythrocyte oxidative stress (as determined by reduced glutathione [GSH], malondialdehyde and methaemoglobin levels) and vascular events (D-dimer, homocysteine and whole blood viscosity) were measured. Statistical analysis was by binomial logistic regression modelling with forward likelihood ratio step procedures. A combination of BGL, BP, erythrocyte GSH and TC gave the best group identifications, with 28/34 (82.4%) and 29/37 (78.4%) members correctly identified in the preDM and DM + CVD groups, respectively. Six of the 34 (17.6%) prediabetes individuals were logistically identified as having diabetic macrovascular complications, but clinically did not qualify for CVD intervention under current screening models. The authors propose that a combination of BGL, BP, erythrocyte GSH and TC can provide a clinically acceptable standard for identifying CVD risk in individuals with prediabetes. This model provides a tool for early identification and targeted intervention in individuals with subclinical diabetes who are at risk of CVD.

Oxidative damage indices for the assessment of subclinical diabetic macrovascular complications.

Subclinical cardiovascular disease (SCVD), including complications in diabetes, is associated with oxidative damage and precedes future cardiovascular disease (CVD). Hence, assessment and management of oxidative damage is imperative. This study investigates biomarkers associated with CVD, diabetes and oxidative stress in order to determine a set of indices that could be useful to assess oxidative damage in diabetic macrovascular pathogenesis. A total of 266 participants were selected and divided into seven groups (control, family history of diabetes, prediabetes, prediabetes with CVD, diabetes mellitus [DM], DM+CVD and CVD) based on clinical history/status. Blood glucose (BG) level, erythrocyte glutathione (GSH), malondialdehyde, methaemoglobin, D-dimer, homocysteine, blood viscosity and cholesterol profile were determined. Factorial MANOVA and independent univariate analyses were performed. Prevalence of significant biomarkers was assessed following a 3.5-year retrospective study. Multivariate analysis showed statistically significant differences between groups (P < 0.0001) with post hoc tests identifying a statistically significant association for BG level (P < 0.0001), GSH (P < 0.0001), D-dimer (P < 0.02) and total cholesterol (P < 0.0001). Of the subjects who showed hyperglycaemia-associated progression in clinical and biochemistry status, 89% had low-level GSH and 44% had high-level D-dimer. Four individuals exhibited prediabetic status at some stage and would qualify for macrovascular disease intervention. The results of this study suggest that BG level, D-dimer, GSH and total cholesterol contribute significantly to a diabetic oxidative damage panel of markers that could assist in evidence-based pharmacological intervention with anti-aggregation and/or antioxidant agents against future CVD in diabetes.

Erythrocyte oxidative stress in clinical management of diabetes and its cardiovascular complications.

Diabetes mellitus is a chronic disease in its own right and is also regarded as a cardiovascular risk factor as well as a cardiovascular disease, due to its ability to progress to a stage of cardiovascular co-morbidity. The pathophysiology of cardiovascular complications in diabetes is reported to involve hyperglycaemia-induced oxidative stress. The erythrocyte has an array of endogenous antioxidants involved in quenching oxidant production and the exponential chain reactions in diabetes. When the erythrocyte is oxidatively stressed, as demonstrated by depleted reduced glutathione and/or increased malondialdehyde in its cell membrane, the risk of diabetes progression and its cardiovascular sequelae, including atherosclerosis and coronary artery disease, is increased. Virtually all studies that determined erythrocyte malondialdehyde and glutathione in diabetes show consistently increased and reduced levels, respectively. Furthermore, cardiovascular complications of diabetes are reported to commence at the prediabetes stage. Current coronary artery disease screening programmes based on the presence of two or more risk factors are failing to identify those with increased risk of diabetes and cardiovascular complications, thereby limiting early interventions. Screening that includes erythrocyte oxidative stress determination may provide an additional marker for both preclinical and advanced disease. In this review, a concise description of the involvement of erythrocyte oxidative stress in diabetes mellitus and its cardiovascular sequelae is presented. Antioxidant action and interaction in the erythrocyte are also described, with emphasis on why current coronary artery disease screening markers cannot be regarded as erythrocyte oxidative stress markers.

Interaction of homocysteine, glutathione and 8-hydroxy-2'-deoxyguanosine in metabolic syndrome progression.

PURPOSE: The role of homocysteine (Hcy) and associated oxidative stress processes in the metabolic syndrome (MetS) continuum has not been explored extensively. Changes in Hcy and associated oxidative stress in relation to the number of metabolic syndrome factors present are explored in this study. METHOD: Participants (n=266) attending a rural diabetes screening clinic had their medical history recorded as well as body mass index, Hcy, glucose, cholesterol, glutathione (GSH), and 8-hydroxy-2-deoxyguanosine (8-OHdG) measured. RESULT: A significant elevation in Hcy (9.5µmol/L ±2 vs. 10.6µmol/L ±3, p=0.03) and 8-OHdG (307pg/mL ±516 vs. 1130pg/mL ±1155, p=0.0001) was observed between the noMetS and MetS groups. Hcy increased with the addition of MetS factors paralleled by 8-OHdG and GSH. A dramatic increase was seen in 8-OHdG, nearly doubling between 2 MetS and 3 MetS factors present (p=0.0001). CONCLUSION: Homocysteine may be a useful marker together with 8-OHdG in assessing the extent of metabolic syndrome in a rural population.

Predicting depressed patients with suicidal ideation from ECG recordings.

Globally suicidal behavior is the third most common cause of death among patients with major depressive disorder (MDD). This study presents multi-lag tone-entropy (T-E) analysis of heart rate variability (HRV) as a screening tool for identifying MDD patients with suicidal ideation. Sixty-one ECG recordings (10 min) were acquired and analyzed from control subjects (29 CONT), 16 MDD subjects with (MDDSI+) and 16 without suicidal ideation (MDDSI-). After ECG preprocessing, tone and entropy values were calculated for multiple lags (m: 1-10). The MDDSI+ group was found to have a higher mean tone value compared to that of the MDDSI- group for lags 1-8, whereas the mean entropy value was lower in MDDSI+ than that in CONT group at all lags (1-10). Leave-one-out cross-validation tests, using a classification and regression tree (CART), obtained 94.83 % accuracy in predicting MDDSI+ subjects by using a combination of tone and entropy values at all lags and including demographic factors (age, BMI and waist circumference) compared to results with time and frequency domain HRV analysis. The results of this pilot study demonstrate the usefulness of multi-lag T-E analysis in identifying MDD patients with suicidal ideation and highlight the change in autonomic nervous system modulation of the heart rate associated with depression and suicidal ideation.

Identifying depressed patients with and without suicidal ideation by finger photo-plethysmography.

Major Depressive Disorder (MDD) is a serious mental disorder that if untreated not only affects physical health but also has a high risk of suicide. While the neurophysiological phenomena that contribute to the formation of Suicidal Ideation (SI) are still ill-defined, clear links between MDD and cardiovascular disease have been reported. The aim of this study is to extract suitable features from arterial pulse signals with a view to predicting SI within MDD and control groups. Sixteen unmedicated MDD patients with a history of SI (MDDSI+), sixteen without SI (MDDSI-) and twenty-nine healthy subjects (CONT) were recruited at a psychiatric clinic in the UAE. Depression severity and SI were assessed using the Hamilton Depression Rating Scale and Beck Depression Inventory. Pulse Wave Amplitude (PWA) was calculated as the difference between the peak (Systole) and the valley (Diastole) of the arterial pulse within each cardiac cycle. Then, 2D Tone-Entropy (TE) features were extracted from the Systole, Diastole and PWA time series. The TE features extracted from Diastole were the best markers for predicting MDDSI+. The overall classification accuracies of Classification and Regression Tree (CART) model by using TE features of Systole, Diastole and PWA were 88.52%, 90.2% and 88.52% respectively. When all TE features were combined, accuracy increased up to 93.44% in identifying MDDSI+/MDDSI-/Control groups.

Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes--Biomarkers as a possible tool for early disease detection for rural screening.

OBJECTIVES: This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes. DESIGN AND METHODS: Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects. RESULTS: While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant. CONCLUSIONS: The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings.

Dye-coupling among neurons of the rat locus coeruleus during postnatal development.

Simultaneous recordings from pairs of locus coeruleus neurons in neonatal rat brain slices previously demonstrated synchronous, subthreshold oscillations of membrane potential (rats < 24 days old) and electronic-coupling between 40% of pairs of neurons from rats less than 10 days old. In the present study, slices from 1-21 day-old rats were stained with avidin-HRP-diaminobenzidine only if a single neuron per slice was impaled for longer than 10 min using an electrode containing biocytin. In slices from rats less than one week old, multiple stained neurons (3.8 +/- 0.6 neurons/slice) were observed in 10 of 11 slices. Apparent contacts between stained neurons were observed at varying distances along dendrites. In rats older than one week significantly fewer multiple stained neurons were observed (three of 20 slices). The proportion of neurons displaying spontaneous subthreshold oscillations of membrane potential decreased with age, and the frequencies of subthreshold oscillations of membrane potential and entrained action potentials increased with age. The presence of multiple stained neurons was not correlated with the occurrence of subthreshold oscillations, cell input resistance, or the number of coupled neurons predicted from the shape of electronic potentials. In recordings from neurons displaying subthreshold oscillations, input resistance was lower and the number of coupled neurons predicted from electrotonic potentials was greater than in those without oscillations. These results suggest that low resistance pathways are common between locus coeruleus neurons in brain slices from rats younger than about one week old, consistent with previous electrotonic-coupling studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurons and fractals: how reliable and useful are calculations of fractal dimensions?

In the past 15 years it has become possible to determine the fractal dimension (Df) of complex objects, including neurons, by automated image analysis methods. However, there are many unresolved issues that need to be addressed. In this paper we discuss how the Df calculated by different methods may vary and how fractal analysis may be of use for retinal ganglion cell characterization. The goal of this work was to acknowledge inherent sources of variation during measurement and evaluate current fractal analysis methods for describing structure. Our results show that different algorithms and even the same algorithm performed by different computer programs and/or experimenters may give different but consistent numerical values. All described methods demonstrated their suitability for classifying cat retinal ganglion cells into distinct groups. Our results reinforce the idea that comparison of measurements of different profiles using the same measurement method may be useful and valid even if an exact numeric value of the dimension is not realised in practice.

A method to determine the fractal dimension of the cross-sectional jaggedness of the infarct scar edge.

This study describes the use of a shareware software package available from the National Institutes of Health for computing the fractal dimension. Specifically, when fractal analysis is used in its correct context it provides for a quantitative description of the space filling properties of two-dimensional objects. A rabbit model of post myocardial infarction is described where the cross-sectional infarct edge is reconstructed and its jaggedness determined by calculating its fractal dimension via the pixel dilation method. The fractal dimensions of the anterior and posterior lateral infarct edges were calculated to have a mean of 1.16 and 1.29, respectively. In conclusion, the fractal technique can be used to describe the complex jaggedness of the infarct edge. This case study also illustrates the fact that the complexity of an infarcted area is not uniform across the scar. For example, we found that the space filling properties of the anterior and posterior borders of a myocardial infarct can differ by more than 2-fold.

Cross-sectional infarct edge jaggedness does not influence ventricular electrical stability in a rabbit model of late myocardial infarct healing.

Previous studies have suggested that the jaggedness of the healed or healing infarct edge influences cardiac electrical stability. However, these findings have been based on histological observations rather than quantitative measurements. The aim of this study was to assess infarct jaggedness by calculating its fractal dimension and to examine how this influences cardiac electrical stability during late infarct healing in the rabbit. Using programmed electrical stimulation, it was found that the fractal dimension did not differ significantly in 19 rabbits that had inducible ventricular tachycardia and 16 that did not. We conclude from these studies in the mature rabbit that infarct edge jaggedness does not influence the ease with which ventricular tachycardia is induced during late myocardial infarct healing.

Risk stratification of cardiac autonomic neuropathy based on multi-lag Tone-Entropy.

Cardiac autonomic neuropathy (CAN) is an irreversible condition affecting the autonomic nervous system, which leads to abnormal functioning of the visceral organs and affects critical body functions such as blood pressure, heart rate and kidney filtration. This study presents multi-lag Tone-Entropy (T-E) analysis of heart rate variability (HRV) at multiple lags as a screening tool for CAN. A total of 41 ECG recordings were acquired from diabetic subjects with definite CAN (CAN+) and without CAN (CAN-) and analyzed. Tone and entropy values of each patient were calculated for different beat sequence lengths (len: 50-900) and lags (m: 1-8). The CAN- group was found to have a lower mean tone value compared to that of CAN+ group for all m and len, whereas the mean entropy value was higher in CAN- than that in CAN+ group. Leave-one-out (LOO) cross-validation tests using a quadratic discriminant (QD) classifier were applied to investigate the performance of multi-lag T-E features. We obtained 100 % accuracy for tone and entropy with len = 250 and m = {2, 3} settings, which is better than the performance of T-E technique based on lag m = 1. The results demonstrate the usefulness of multi-lag T-E analysis over single lag analysis in CAN diagnosis for risk stratification and highlight the change in autonomic nervous system modulation of the heart rate associated with cardiac autonomic neuropathy.

Points of interest and visual dictionaries for automatic retinal lesion detection.

In this paper, we present an algorithm to detect the presence of diabetic retinopathy (DR)-related lesions from fundus images based on a common analytical approach that is capable of identifying both red and bright lesions without requiring specific pre- or postprocessing. Our solution constructs a visual word dictionary representing points of interest (PoIs) located within regions marked by specialists that contain lesions associated with DR and classifies the fundus images based on the presence or absence of these PoIs as normal or DR-related pathology. The novelty of our approach is in locating DR lesions in the optic fundus images using visual words that combines feature information contained within the images in a framework easily extendible to different types of retinal lesions or pathologies and builds a specific projection space for each class of interest (e.g., white lesions such as exudates or normal regions) instead of a common dictionary for all classes. The visual words dictionary was applied to classifying bright and red lesions with classical cross validation and cross dataset validation to indicate the robustness of this approach. We obtained an area under the curve (AUC) of 95.3% for white lesion detection and an AUC of 93.3% for red lesion detection using fivefold cross validation and our own data consisting of 687 images of normal retinae, 245 images with bright lesions, 191 with red lesions, and 109 with signs of both bright and red lesions. For cross dataset analysis, the visual dictionary also achieves compelling results using our images as the training set and the RetiDB and Messidor images as test sets. In this case, the image classification resulted in an AUC of 88.1% when classifying the RetiDB dataset and in an AUC of 89.3% when classifying the Messidor dataset, both cases for bright lesion detection. The results indicate the potential for training with different acquisition images under different setup conditions with a high accuracy of referral based on the presence of either red or bright lesions or both. The robustness of the visual dictionary against image quality (blurring), resolution, and retinal background, makes it a strong candidate for DR screening of large, diverse communities with varying cameras and settings and levels of expertise for image capture.

Chronic high dose captopril decreases total heart rate variability and increases heart rate in C57BL/6J mice.

The effects of high dose captopril, within the therapeutic range, on autonomic activity are unknown in those with normal cardiovascular function. Thus the study aims were to assess the effects of high dose captopril on autonomic function in mice. Autonomic activity was measured using heart rate variability (HRV). ECG recordings were obtained from 18 Male C57BL/6J mice (20-25 g) subdivided into control (N=8) or mice receiving oral captopril (0.688 mg/ml captopril in the drinking water for 6 weeks, N=10). HRV results for linear and non-linear parameters were attenuated following chronic captopril for 6 weeks compared to control. Captopril was associated with a trend for an increase in average heart rate and approximate entropy (ApEn), a non-linear measure of HRV decreased significantly compared to control (p<0.05). In conclusion high dose captopril reduces total HRV and increases heart rate in normotensive mice with normal cardiac function.

Use of fractal theory in neuroscience: methods, advantages, and potential problems.

Fractal analysis has already found widespread application in the field of neuroscience and is being used in many other areas. Applications are many and include ion channel kinetics of biological membranes and classification of neurons according to their branching characteristics. In this article we review some practical methods that are now available to allow the determination of the complexity and scaling relationships of anatomical and physiological patterns. The problems of describing fractal dimensions are discussed and the concept of fractal dimensionality is introduced. Several related methodological considerations, such as preparation of the image and estimation of the fractal dimensions from the data points, as well as the advantages and problems of fractal geometric analysis, are discussed.