Lifetime glucocorticoid profiles in baleen of right whale calves: Potential relationships to chronic stress of repeated wounding by Kelp Gulls

Baleen tissue accumulates stress hormones (glucocorticoids, GC) as it grows, along with other adrenal, gonadal and thyroid hormones. The hormones are deposited in a linear fashion such that a single plate of baleen allows retrospective assessment and evaluation of long-term trends in the whales´ physiological condition. In whale calves, a single piece of baleen contains hormones deposited across the lifespan of the animal, with the tip of the baleen representing prenatally grown baleen. This suggests that baleen recovered from stranded carcasses of whale calves could be used to examine lifetime patterns of stress physiology. Here we report lifetime profiles of cortisol and corticosterone in baleen of a North Atlantic right whale ("NARW" - Eubalaena glacialis) calf that died from a vessel strike, as well as four southern right whale ("SRW" - Eubalaena australis) calves that were found dead with varying severity of chronic wounding from Kelp Gull (Larus dominicanus) attacks. In all five calves, prenatally grown baleen exhibited a distinctive profile of elevated glucocorticoids that declined shortly before birth, similar to GC profiles reported from baleen of pregnant females. After birth, GC profiles in calf baleen corresponded with the degree of wounding. The NARW calf and two SRW calves with no or few gull wounds had relatively low and constant GC content throughout life, while two SRW calves with high numbers of gull wounds had pronounced elevations in baleen GC content in postnatal baleen followed by a precipitous decline shortly before death, a profile suggestive of prolonged chronic stress. Baleen samples may present a promising and valuable tool for defining the baseline physiology of whale calves and may prove useful for addressing conservation-relevant questions such as distinguishing acute from chronic stress and, potentially, determining cause of death.Fil: Ajó, Alejandro A. Fernández. Northern Arizona University; Estados UnidosFil: Hunt, Kathleen E.. Northern Arizona University; Estados UnidosFil: Uhart, Marcela María. University of California at Davis; Estados UnidosFil: Rowntree, Victoria. University of Utah; Estados UnidosFil: Sironi, Mariano. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Diversidad Biológica y Ecológica; Argentina. Instituto de Conservación de Ballenas; ArgentinaFil: Marón, Carina Flavia. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Diversidad Biológica y Ecológica; Argentina. Instituto de Conservación de Ballenas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Martino, Matias. Southern Right Whale Health Monitoring Program; ArgentinaFil: Buck, Charles Loren. Northern Arizona University; Estados Unido

High-frequency ultrasound imaging in wound assessment: current perspectives

Non-invasive imaging modalities for wound assessment have become increasingly popular over the past two decades. The wounds can be developed superficially or from within deep tissues, depending on the nature of the dominant risk factors. Developing a reproducible quantitative method to assess wound-healing status has demonstrated to be a convoluted task. Advances in High-Frequency Ultrasound (HFU) skin scanners have expanded their application as they are cost-effective and reproducible diagnostic tools in dermatology, including for the measurement of skin thickness, the assessment of skin tumours, the estimation of the volume of melanoma and non-melanoma skin cancers, the visualisation of skin structure and the monitoring of the healing of acute and chronic wounds. Previous studies have revealed that HFU images carry dominant parameters and depict the phenomena occurring within deep tissue layers during the wound-healing process. However, the investigations have mostly focussed on the validation of HFU images, and few studies have utilised HFU imaging in quantitative assessment of wound generation and healing. This paper is an introductory review of the important studies proposed by the researchers in the context of wound assessment. The principles of dermasonography are briefly explained, followed by a review of the relevant literature that investigated the wound-healing process and tissue structures within the wound using HFU imaging

Cost effectiveness analysis of larval therapy for leg ulcers

Objective: To assess the cost effectiveness of larval therapy compared with hydrogel in the management of leg ulcers. Design: Cost effectiveness and cost utility analyses carried out alongside a pragmatic multicentre, randomised, open trial with equal randomisation. Population: Intention to treat population comprising 267 patients with a venous or mixed venous and arterial ulcers with at least 25% coverage of slough or necrotic tissue. Interventions: Patients were randomly allocated to debridement with bagged larvae, loose larvae, or hydrogel. Main outcome measure: The time horizon was 12 months and costs were estimated from the UK National Health Service perspective. Cost effectiveness outcomes are expressed in terms of incremental costs per ulcer-free day (cost effectiveness analysis) and incremental costs per quality adjusted life years (cost utility analysis). Results: The larvae arms were pooled for the main analysis. Treatment with larval therapy cost, on average, 96.70 pound ((sic)109.61; $140.57) more per participant per year (95% confidence interval -491.9 pound to 685.8) pound than treatment with hydrogel. Participants treated with larval therapy healed, on average, 2.42 days before those in the hydrogel arm (95% confidence interval -0.95 to 31. 91 days) and had a slightly better health related quality of life, as the annual difference in QALYs was 0.011 (95% confidence interval -0.067 to 0.071). However, none of these differences was statistically significant. The incremental cost effectiveness ratio for the base case analysis was estimated at 8826 pound per QALY gained and 40 pound per ulcer-free day. Considerable uncertainty surrounds the outcome estimates. Conclusions: Debridement of sloughy or necrotic leg ulcers with larval therapy is likely to produce similar health benefits and have similar costs to treatment with hydrogel. Trial registration: Current Controlled Trials ISRCTN55114812 and National Research Register N0484123692

Larval therapy for leg ulcers (VenUS II) : randomised controlled trial

Objective To compare the clinical effectiveness of larval therapy with a standard debridement technique (hydrogel) for sloughy or necrotic leg ulcers. Design Pragmatic, three armed randomised controlled trial. Setting Community nurse led services, hospital wards, and hospital outpatient leg ulcer clinics in urban and rural settings, United Kingdom. Participants 267 patients with at least one venous or mixed venous and arterial ulcer with at least 25% coverage of slough or necrotic tissue, and an ankle brachial pressure index of 0.6 or more. Interventions Loose larvae, bagged larvae, and hydrogel. Main outcome measures The primary outcome was time to healing of the largest eligible ulcer. Secondary outcomes were time to debridement, health related quality of life (SF-12), bacterial load, presence of meticillin resistant Staphylococcus aureus, adverse events, and ulcer related pain (visual analogue scale, from 0 mm for no pain to 150 mm for worst pain imaginable). Results Time to healing was not significantly different between the loose or bagged larvae group and the hydrogel group (hazard ratio for healing using larvae v hydrogel 1.13, 95% confidence interval 0.76 to 1.68; P=0.54). Larval therapy significantly reduced the time to debridement (2.31, 1.65 to 3.2; P<0.001). Health related quality of life and change in bacterial load over time were not significantly different between the groups. 6.7% of participants had MRSA at baseline. No difference was found between larval therapy and hydrogel in their ability to eradicate MRSA by the end of the debridement phase (75% (9/12) v 50% (3/6); P=0.34), although this comparison was underpowered. Mean ulcer related pain scores were higher in either larvae group compared with hydrogel (mean difference in pain score: loose larvae v hydrogel 46.74 (95% confidence interval 32.44 to 61.04), P<0.001; bagged larvae v hydrogel 38.58 (23.46 to 53.70), P<0.001). Conclusions Larval therapy did not improve the rate of healing of sloughy or necrotic leg ulcers or reduce bacterial load compared with hydrogel but did significantly reduce the time to debridement and increase ulcer pain. Trial registration Current Controlled Trials ISRCTN55114812 and National Research Register N0484123692

Increased burn healing time is associated with higher Vancouver Scar Scale score

Increased burn wound healing time has been shown to influence abnormal scarring. This study hypothesized that scar severity increases commensurate to the increase in time to healing (TTH) of the wound. Wound healing and scar data from burn patients treated by the Burn Service of Western Australia at Royal Perth Hospital were examined. The relationship between TTH and scar severity, as assessed by the modified Vancouver Scar Scale (mVSS), was modelled using regression analysis. Interaction terms evaluated the effect of surgery and total body surface area – burn (TBSA) on the main relationship. Maximum likelihood estimation was used to account for potential bias from missing independent variable data. The sample had a median age of 34 years, TTH of 24 days, TBSA of 3% and length of stay of five days, 70% were men and 71% had burn surgery. For each additional day of TTH, the mVSS score increased by 0.11 points (P ⩽ 0.001) per day in the first 21 days and 0.02 points per day thereafter (P = 0.004). The relationship remained stable in spite of TBSA or surgical intervention. Investigation of the effect of missing data revealed the primary model underestimated the strength of the association. An increase in TTH within 21 days of injury is associated with an increase in mVSS or reduced scar quality. The results confirm that efforts should be directed toward healing burn wounds as early as possible

Development and characterisation of a novel three-dimensional inter-kingdom wound biofilm model

Chronic diabetic foot ulcers are frequently colonised and infected by polymicrobial biofilms that ultimately prevent healing. This study aimed to create a novel in vitro inter-kingdom wound biofilm model on complex hydrogel-based cellulose substrata to test commonly used topical wound treatments. Inter-kingdom triadic biofilms composed of Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus were shown to be quantitatively greater in this model compared to a simple substratum when assessed by conventional culture, metabolic dye and live dead qPCR. These biofilms were both structurally complex and compositionally dynamic in response to topical therapy, so when treated with either chlorhexidine or povidone iodine, principal component analysis revealed that the 3-D cellulose model was minimally impacted compared to the simple substratum model. This study highlights the importance of biofilm substratum and inclusion of relevant polymicrobial and inter-kingdom components, as these impact penetration and efficacy of topical antiseptics

Regulation of wound strength by Ocimum sanctum: in silico and in vivo evidences

Background: The present work has been an attempt to facilitate the scientific understanding of the wound strength by Ocimum sanctum (OS, holy basil) a traditional knowledge practiced since ancient times in India.Methods: The in vivo Incision (wound strength) and Dead space wound models (biochemical estimation of components of ECM) in rats and  In silico method, where one of the target proteins from each class of MMPs involved in wound strength was selected for molecular docking with eugenol (one of the flavonoid present in OS).Results: Molecular docking showed that eugenol was able to inhibit all selected MMPs, i.e. collagenase (-6.37 Kcal/mol), gelatinase (-5.99 Kcal/mol), elastase (-6.31 Kcal/mol) and stromelysin (-5.79 Kcal/mol). Ethanolic extract of Ocimum sanctum (OSE, 200-800 mg/kg) when administered as suspension showed dose-dependent increase in wound breaking strength in in vivo Incision wound rat model. OSE 400 mg/kg produced a significant increase in protein and collagen constituents like hydroxyproline, hexuronic acid and hexosamine in the connective tissue content of extracellular matrix when studied in Dead space wound model in rat.Conclusions: The present study is an attempt to correlate the in vivo findings on wound strength promoting activity by Ocimum sanctum with in silico tools

Monitoring Wound Healing with Contactless Measurements and Augmented Reality

Objective: This work presents a device for non-invasive wound parameters assessment, designed to overcome the drawbacks of traditional methods, which are mostly rough, inaccurate, and painful for the patient. The device estimates the morphological parameters of the wound and provides augmented reality (AR) visual feedback on the wound healing status by projecting the wound border acquired during the last examination, thus improving doctor-patient communication. Methods: An accurate 3D model of the wound is created by stereophotogrammetry and refined through self-organizing maps. The 3D model is used to estimate physical parameters for wound healing assessment and integrates AR functionalities based on a miniaturized projector. The physical parameter estimation functionalities are evaluated in terms of precision, accuracy, inter-operator variability, and repeatability, whereas AR wound border projection is evaluated in terms of accuracy on the same phantom. Results: The accuracy and precision of the device are respectively 2% and 1.2% for linear parameters, and 1.7% and 1.3% for area and volume. The AR projection shows an error distance &lt;1 mm. No statistical difference was found between the measurements of different operators. Conclusion: The device has proven to be an objective and non-operator-dependent tool for assessing the morphological parameters of the wound. Comparison with non-contact devices shows improved accuracy, offering reliable and rigorous measurements. Clinical Impact: Chronic wounds represent a significant health problem with high recurrence rates due to the ageing of the population and diseases such as diabetes and obesity. The device presented in this work provides an easy-to-use non-invasive tool to obtain useful information for treatment

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total