ORCID Profile
0000-0003-2892-6238
Current Organisations
Korea Astronomy and Space Science Institute
,
Hull York Medical School
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Forensic Chemistry | Animal Developmental and Reproductive Biology | Medical Devices | Biochemistry and Cell Biology | Public Health and Health Services | Biomedical Engineering | Crop and Pasture Biochemistry and Physiology | Environmental and Occupational Health and Safety | Environmental Monitoring | Dermatology | Medical Biotechnology Diagnostics (incl. Biosensors) | Biochemistry and Cell Biology not elsewhere classified |
Public Health (excl. Specific Population Health) not elsewhere classified | Diagnostic Methods | Skin and Related Disorders | Substance Abuse | Expanding Knowledge in the Agricultural and Veterinary Sciences | Cancer and Related Disorders | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Medical and Health Sciences
Publisher: American Medical Association (AMA)
Date: 10-2014
Publisher: Elsevier BV
Date: 10-2022
Publisher: Wiley
Date: 29-06-2012
DOI: 10.1111/J.1600-0625.2012.01543.X
Abstract: It has been shown that gene mutations which drive the development of malignant melanoma (MM) in humans also lead to emergence of MM when engineered mice. However, little attention has been paid to the clinical and histopathological features of melanocytic lesions and their natural history in a given mouse model. This knowledge is crucial to enable us to understand how engineered mutations influence the initiation and evolution of melanocytic lesions, and/or for the use of mice as a preclinical model to test specific treatments. We recently reported the development of melanocytic proliferations along the spectrum of naevi to MM in a Cdk4 ( R24C/R24C ) ::Tyr- NRAS ( Q ) ( 61K ) mouse model. In this study, we followed the development of lesions over time using digital photography and dermoscopy with the aim to correlate the clinical and histopathological features of lesions developing in this model. We identified two types of lesions. The first are slow-growing dermal MMs that emanate from dermal naevi. The second did not emanate from naevi, grew rapidly, and appeared to be solely confined to the subcutaneous fat. We present a simple staging system for the MMs that progress from naevi, based on depth of extension into the dermis and subcutis. This represents a blueprint for documentation and follow-up of MMs in the live animal, which is critical for the proper use of murine melanoma models.
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.JMOLDX.2022.09.008
Abstract: Skin cancer is a significant and increasing global health burden. Although the current diagnostic workflow is robust and able to provide clinically actionable results, it is subject to notable limitations. The training and expertise required for accurate diagnoses using conventional skin cancer diagnostics are significant, and patient access to this workflow can be limited by geographic location or unforeseen events, such as coronavirus disease 2019 (COVID-19). Molecular biomarkers have transformed diagnostics and treatment delivery in oncology. With rapid advancements in molecular biology techniques, understanding of the underlying molecular mechanism of cancer pathologies has deepened, yielding biomarkers that can be used to monitor the course of malignant diseases. Herein, commercially available, clinically validated, and emerging skin cancer molecular biomarkers are reviewed. The qualities of an ideal molecular biomarker are defined. The potential benefits and limitations of applying molecular biomarker testing over the course of skin cancer from susceptibility to treatment are explored, with a view to outlining a future model of molecular biomarker skin cancer diagnostics.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.JCONREL.2013.07.025
Abstract: The delivery of therapeutics and cosmaceuticals into and/or through the skin is hindered by epidermal barriers. To overcome the skin's barriers we have developed a novel cutaneous delivery method using high aspect ratio elongate microparticles (EMPs). Using ex vivo and in vivo pig skin we assess the penetration and delivery characteristics of the elongate microparticles. With reflectance confocal microscopy we observed that the elongate microparticles successfully penetrated the epidermis and upper dermis. Delivery was then assessed using two different length populations of EMPs, comparing their delivery profile to topical alone using sodium fluorescein and confocal microscopy. We observed a relatively uniform and continuous delivery profile in the EMP treated area within the upper layers of the skin--up to seven times greater than topical alone. Finally, we delivered two therapeutically relevant compounds (Vitamins A and B3), showing enhanced delivery using the EMPs. To our knowledge this is the first report using high aspect ratio elongate microparticles in this manner for enhanced topical delivery to the skin.
Publisher: SPIE
Date: 20-03-2015
DOI: 10.1117/12.2081737
Publisher: Wiley
Date: 11-12-2014
DOI: 10.1111/PCMR.12195
Publisher: Wiley
Date: 27-12-2021
DOI: 10.1002/MDS3.10160
Publisher: Elsevier
Date: 2016
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2008
DOI: 10.1167/IOVS.07-0632
Publisher: MyJove Corporation
Date: 21-02-2019
DOI: 10.3791/58614
Abstract: Conventional skin biopsy limits the clinical research that involves cosmetically sensitive areas or pediatric applications due to its invasiveness. Here, we describe the protocol for using an absorbent microneedle-based device, absorbent microbiopsy, for minimally invasive s ling of skin and blood mixture. Our goal is to help facilitate rapid progress in clinical research, the establishment of biomarkers for skin disease and reducing the risk for clinical research participants. In contrast to conventional skin biopsy techniques, the absorbent microbiopsy can be performed within seconds and does not require intensive training due to its simple design. In this report, we describe the use of absorbent microbiopsy, including loading and application, on a volunteer. Then, we show how to isolate RNA from the absorbed s le. Finally, we demonstrate the use of quantitative reverse transcription PCR (RT-qPCR) to quantify mRNA expression levels of both blood (CD3E and CD19) and skin (KRT14 and TYR). The methods that we describe utilize off the shelf kits and reagents. This protocol offers a minimally invasive approach for simultaneous s ling of skin and blood within the same absorbent microbiopsy matrix. We have found human ethics committees, clinicians and volunteers to be supportive of this approach to dermatological research.
Publisher: Springer Science and Business Media LLC
Date: 20-10-2016
Publisher: Public Library of Science (PLoS)
Date: 18-04-2016
Publisher: Wiley
Date: 23-10-2006
DOI: 10.1002/DVDY.20988
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.3109/17435390.2011.569092
Abstract: Systematic studies probing the effects of nanoparticle surface modification and formulation pH are important in nanotoxicology and nanomedicine. In this study, we use laser-scanning fluorescence confocal microscopy to evaluate nanoparticle penetration in viable excised human skin that was intact or tape-stripped. Quantum dot (QD) fluorescent nanoparticles with three surface modifications: Polyethylene glycol (PEG), PEG-amine (PEG-NH₂) and PEG-carboxyl (PEG-COOH) were evaluated for human skin penetration from aqueous solutions at pH 7.0 and at pHs of solutions provided by the QD manufacturer: 8.3 (PEG, PEG-NH₂) and 9.0 (PEG-COOH). There was some penetration into intact viable epidermis of skin for the PEG-QD at pH 8.3, but not at pH 7.0 nor for any other QD at the pHs used. Upon tape stripping 30 strips of stratum corneum, all QDs penetrated through the viable epidermis and into the upper dermis within 24 h.
Publisher: JMIR Publications Inc.
Date: 20-06-2022
DOI: 10.2196/37034
Abstract: Digital 3D total-body photography of the skin surface is an emerging imaging modality that can facilitate the identification of new and changing nevi. We aimed to describe the experiences of study participants drawn from the general population who were provided 3D total-body photography and dermoscopy for the monitoring of nevi. A population-based prospective study of adults aged 20-70 years from South East Queensland, Australia was conducted. Participants underwent 3D total-body photography and dermoscopy every 6 months over a 3-year period. Participants were asked to provide closed and open-ended feedback on their 3D total-body photography and dermoscopy experience (eg, comfort, trust, intended future use, and willingness to pay) at the halfway study time point (18 months) and final study time point (36 months). We assessed changes in participants’ reported experience of 3D total-body photography, and patient characteristics associated with patient experience at the end of the study (36 months) were analyzed. A total of 149 participants completed the surveys at both the 18- and 36-month time points (median age 55, range 23-70 years n=94, 63.1% were male). At the 18-month time point, most participants (n=103, 69.1%) stated they completely trusted 3D total-body imaging for the diagnosis and monitoring of their nevi, and this did not change at the 36-month (n=104, 69.8%) time point. The majority of participants reported that they were very comfortable or comfortable with the technology at both the 18- (n=138, 92.6%) and 36-month (n=140, 94%) time points, respectively albeit, the number of participants reporting that they were very comfortable reduced significantly between the 18- and 36-month time points, from 71.1% (n=106) to 61.1% (n=91 P=.01). Almost all participants (n=140, 94%) would consider using this technology if it were to become commercially available, and this did not change during the two study time points. Half of the participants (n=74) cited barriers to participating in 3D total-body photography, including trust in the ability of this technology to detect and monitor suspicious lesions, digital privacy, cost, and travel requirements. The majority of participants expressed positive attitudes toward 3D total-body photography for the monitoring of their moles. Half of the participants identified potential barriers to uptake.
Publisher: The Royal Society of Chemistry
Date: 06-12-2013
DOI: 10.1039/9781849734639-00169
Abstract: Proteins and peptides are coming of age as targeted biological therapies. A broad range of peptides have now been approved by the FDA and other regulatory agencies for use as therapeutics. Likewise, large proteins such as infliximab and botox are commonly used to treat skin conditions. The most widely used delivery approach for peptides and proteins is parenteral injection, largely due to oral instability and the lack of a suitable alternative. Intense research is being done to improve the short half-lives of these biological therapies and find suitable alternative delivery routes. Transdermal delivery holds promise as an improved delivery route because the skin has low levels of enzymatic activity and can help drugs avoid first-pass metabolism. Further, topical delivery has the potential for direct treatment of skin disease for both therapeutic and cosmetic applications.
Publisher: Wiley
Date: 30-08-2020
DOI: 10.1111/ICS.12646
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2002
Abstract: Data suggesting that the hepatitis C virus (HCV) core protein influences normal cellular processes remain controversial. To determine the effects of core on cellular gene expression in hepatocytes, we developed a human hepatoma (Huh7)-derived cell line with tightly regulated core expression under the control of a tetracycline-regulated promoter. Cells expressing core did not have impaired proliferative abilities. Changes in gene expression profiles in response to core expression were determined using commercial oligonucleotide microarrays (Affymetrix GeneChip). Significant increases were observed in the abundance of mRNA-encoding members of the metallothionein (MT) family, as well as nicotinamide N-methyltransferase (NNMT) and glutathione peroxidase-like protein (GPLP). These changes did not result from removal of tetracycline from growth media, and were confirmed in reverse-transcription polymerase chain reaction (RT-PCR) assays. They suggest that core protein expression leads to intracellular oxidative stress, and that vital cellular functions are, in turn, protected by up-regulation of cellular antioxidant defense mechanisms. In conclusion, these findings can explain many potentially conflicting prior observations concerning the effects of core on cellular physiology, and are of relevance to the role of core protein in the pathogenesis of HCV-related fibrosis and hepatocellular carcinoma.
Publisher: Springer Berlin Heidelberg
Date: 2017
Publisher: Wiley
Date: 17-12-2015
DOI: 10.1002/WNAN.1322
Abstract: There are an abundance of nanoparticle technologies being developed for use as part of therapeutic strategies. This review focuses on a narrow class of metal nanoparticles that have therapeutic potential that is a consequence of elemental composition and size. The most widely known of these are gold nanoshells that have been developed over the last two decades for photothermal ablation in superficial cancers. The therapeutic effect is the outcome of the thickness and diameter of the gold shell that enables fine tuning of the plasmon resonance. When these metal nanoparticles are exposed to the relevant wavelength of light, their temperature rapidly increases. This in turn induces a localized photothermal ablation that kills the surrounding tumor tissue. Similarly, gold nanoparticles have been developed to enhance radiotherapy. The high‐ Z nature of gold dramatically increases the photoelectric cross‐section. Thus, the photoelectric effects are significantly increased. The outcome of these interactions is enhanced tumor killing with lower doses of radiation, all while sparing tissue without gold nanoparticles. Silver nanoparticles have been used for their wound healing properties in addition to enhancing the tumor‐killing effects of anticancer drugs. Finally, platinum nanoparticles are thought to serve as a reservoir for platinum ions that can induce DNA damage in cancer cells. The future is bright with the path to clinical trials is largely cleared for some of the less complex therapeutic metal nanoparticle systems. WIREs Nanomed Nanobiotechnol 2015, 7:428–445. doi: 10.1002/wnan.1322 This article is categorized under: Implantable Materials and Surgical Technologies Nanomaterials and Implants Therapeutic Approaches and Drug Discovery Nanomedicine for Oncologic Disease Implantable Materials and Surgical Technologies Nanoscale Tools and Techniques in Surgery
Publisher: SPIE
Date: 19-04-2017
DOI: 10.1117/12.2256789
Publisher: SPIE-Intl Soc Optical Eng
Date: 03-07-2013
Publisher: SPIE
Date: 07-2004
DOI: 10.1117/12.547922
Publisher: Oxford University Press (OUP)
Date: 09-01-2016
DOI: 10.1111/BJD.14245
Abstract: LEO 43204 is a novel ingenol derivative in development for the treatment of actinic keratosis. To compare the safety and preliminary efficacy of three doses of LEO 43204 with ingenol mebutate in actinic keratoses (AKs). Patients with at least three visible, discrete, nonkeratotic AKs on four separate selected treatment areas on the forearms received LEO 43204 gel (0·025%, 0·05% and 0·075%) and ingenol mebutate 0·05% gel, by investigator-blinded, randomized allocation, for 2 consecutive days. Patients were assessed at 8 weeks. Primary outcomes included maximum composite local skin response (LSR) score and adverse events (AEs). Secondary outcomes included a reduction in the number of visible AKs. Forty patients completed the trial. For all treatments, mean LSR scores peaked at week 1, and were below baseline by week 8. Mean maximum composite LSR scores for LEO 43204 0·025%, 0·05% and 0·075% were 9·2 (Dunnett adjusted P = 0·02), 10·1 (Dunnett adjusted P = 0·90) and 11·2 (Dunnett adjusted P < 0·01), respectively, vs. ingenol mebutate 0·05% gel (10·0). The most frequent AEs across all treatments were application site pruritus, burning sensation and tenderness. Mean reduction in the number of AKs was comparable for ingenol mebutate and the two lowest doses of LEO 43204 (71·9-73·1%), but LEO 43204 0·075% gave a significantly larger reduction (81·8% Dunnett adjusted P = 0·04). LEO 43204 had a similar safety profile to ingenol mebutate and a dose-response relationship for LSRs was demonstrated. The highest LEO 43204 dose (0·075%) significantly reduced the AK count when compared with ingenol mebutate.
Publisher: American Medical Association (AMA)
Date: 09-2013
Publisher: No publisher found
Date: 2013
Publisher: American Medical Association (AMA)
Date: 04-2015
Publisher: Wiley
Date: 16-09-2010
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-05-2015
Publisher: Springer Science and Business Media LLC
Date: 15-08-2019
DOI: 10.1007/S10544-019-0412-Y
Abstract: Conventional skin and blood s ling techniques for disease diagnosis, though effective, are often highly invasive and some even suffer from variations in analysis. With the improvements in molecular detection, the amount of starting s le quantity needed has significantly reduced in some diagnostic procedures, and this has led to an increased interest in micros ling techniques for disease biomarker detection. The miniaturization of s ling platforms driven by micros ling has the potential to shift disease diagnosis and monitoring closer to the point of care. The faster turnaround time for actionable results has improved patient care. The variations in s le quantification and analysis remain a challenge in the micros ling field. The future of micros ling looks promising. Emerging techniques are being clinically tested and monitored by regulatory bodies. This process is leading to safer and more reliable diagnostic platforms. This review discusses the advantages and disadvantages of current skin and blood micros ling techniques.
Publisher: SPIE
Date: 08-02-2007
DOI: 10.1117/12.701645
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 25-06-2013
DOI: 10.1111/EXD.12176
Abstract: Skin photoageing results from a combination of factors including ultraviolet (sun) exposure, leading to significant changes in skin morphology and composition. Conventional methods assessing the degree of photoageing, in particular histopathological assessment involve an invasive multistep process. Advances in microscopy have enabled a shift towards non-invasive in vivo microscopy techniques such as reflectance confocal microscopy (RCM) in this context. Computational image analysis of RCM images has the potential to be of use in the non-invasive assessment of photoageing. In this report, we computationally characterized a clinical RCM data set from younger and older Caucasians with varying levels of photoageing. We identified several mathematical relationships that related to the degree of photoageing as assessed by conventional scoring approaches (clinical photography, SCINEXA and RCM). Furthermore, by combining the mathematical features into a single computational assessment score, we observed significant correlations with conventional RCM (P < 0.0001) and the other clinical assessment techniques.
Publisher: Elsevier BV
Date: 12-2008
Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2020
DOI: 10.1101/2020.12.08.20245829
Abstract: In addition to risking their physical well-being, frontline physicians are enduring significant emotional burden both at work and home during the COVID-19 pandemic. This study aims to investigate the levels of anxiety and depressive symptoms and to identify associated factors among Bangladeshi physicians during the COVID-19 outbreak. A cross-sectional study using an online survey was conducted between April 21 and May 10, 2020. Outcomes assessed included demographic questions, COVID-19 related questions, and the Hospital Anxiety and Depression Scale (HADS). The survey was completed by 412 Bangladeshi physicians. The findings revealed that, in terms of standardized HADS cut-off points, the prevalence of anxiety and depressive symptoms among physicians was 67.72% and 48.5% respectively. Risk factors for higher rates of anxiety or depressive symptoms were: being female, physicians who had experienced COVID-19 like symptoms during the pandemic, those who had not received incentives, those who used self-funded PPE, not received adequate training, lacking perceived self-efficacy to manage COVID -19 positive patients, greater perceived stress of being infected, fear of getting assaulted/humiliated, being more connected with social media, having lower income levels to support the family, feeling more agitated, less than 2 hours of leisure activity per day and short sleep duration. All these factors were found to be positively associated with anxiety and depression in unadjusted and adjusted statistical models. This study identifies a real concern about the prevalence of anxiety and depressive symptoms among Bangladeshi physicians and identifies several associated factors during the COVID-19 pandemic. Given the vulnerability of the physicians in this extraordinary period whilst they are putting their own lives at risk to help people infected by COVID-19, health authorities should address the psychological needs of medical staff and formulate effective strategies to support vital frontline health workers. This study reports a novel and concerning findings on the prevalence of anxiety and depression symptoms with identification of several important associated factors among Bangladeshi physicians during the COVID-19 pandemic. The cross-sectional nature of the study design could not establish causal relationship between the dependent and independent variables. This study was carried out by conducting a web-based survey, which might generate s ling bias by excluding the physicians who do not have access to internet or inactive in social medias, and thus limit the generalizability of the findings.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.JCONREL.2009.06.029
Abstract: Dry-coated microprojections (MPs) deliver vaccine to abundant immunogenic cells within the skin to induce immune responses. Success in this targeted vaccine delivery relies on overcoming the challenges of dry-coating the vaccine onto the very small (<or=90 microm length) and densely packed (approximately 20,000 cm(-2)) MPs. In this paper, we show that a gas-jet drying coating method achieves the desired uniform coating. The coating approach is robustly demonstrated on compounds representative of a range of immunotherapeutics (e.g. DNA, proteins), with each uniformly coated on thousands of MPs. Furthermore, the dry-coating remains intact during skin insertion, and then releases within the wet skin cellular environment within 3 min. Finally, we applied ovalbumin protein coated MP patches to immunise mice, achieving comparable antibody levels (p=0.08) with needle and syringe intramuscular injection. In summary, this paper presents a simple, practical and versatile method to achieve uniform coating on very small and densely packed MPs for a needle-free and targeted vaccine delivery technology.
Publisher: IEEE
Date: 11-2015
Publisher: Public Library of Science (PLoS)
Date: 21-04-2010
Publisher: Wiley
Date: 04-2014
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.IJPHARM.2021.121258
Abstract: Physical drug delivery enhancement in skin has been shown to enhance cosmeceutical actives efficacy. Among the physical drug delivery enhancement technologies, microneedle is the most commercially successful technology. However, there are pros and cons like other physical enhancement technologies including variabilities in penetration depth and lack of efficacy. In this study, three physical topical dug delivery enhancements, elongated microparticles, microneedles and dermaroller, were applied to ex vivo pig skin and compared. The model topical drug that was used is 5-Aminolevulinic acid, the most commonly used photosensitiser prodrug. The skin was pre-treated before mounting on to Franz cell diffusion apparatus. Transdermal epidermal water loss was measured, and receptor fluids were collected at 7 time points for HPLC analysis. The results show that all three technologies disrupted the skin surface. All microporation pre-treatments significantly enhanced mALA cumulative permeation over 8 h (p < 0.001), with the 24x dermaroller significantly greater than 12x dermaroller (p < 0.001) and both dermaroller treatments significantly greater than microneedles and elongated microparticles (p 12x dermaroller > microneedles > elongated microparticles. In conclusion, physical enhancement tools such as microneedles, dermarollers and elongated microparticles demonstrated significant penetration and retention of mALA through/into piglet skin. Further study is needed to determine the cost, dose and patient compliance.
Publisher: Wiley
Date: 26-06-2021
DOI: 10.1002/APP.51314
Abstract: Conducting polymers are promising candidates for wearable devices due to mechanical flexibility combined with electroactivity. While electrochemical measurements have been adopted as a central transduction method in many on‐skin sensors, less studied is the stability of the active materials (in particular poly3,4‐ethylenedioxythiophene, PEDOT) in such systems, particularly for “on‐skin” applications. In this study, several different variants of doped PEDOT are fabricated and characterized in terms of their (electrical, physical, and chemical) stability in biological fluid. PEDOT doped with tosylate (TOS) or polystyrenesulfonate (PSS) are selected as prototypical forms of conducting polymers. These are compared with a new variant of PEDOT co‐doped with both TOS and PSS. Artificial interstitial fluid (aISF) loaded with 1% wt/vol bovine serum albumin is adopted as the testing medium to demonstrate the stability in dermal applications (i.e., conducting polymer microneedles or coatings on microneedles). A range of techniques such as cyclic voltammetry and electrochemical impedance spectroscopy are used to qualify and quantify the stability of the doped conducting polymers. Furthermore, this study is extended by using human skin lysate in the aISF to demonstrate proof‐of‐concept for stable use of PEDOT in wearable “on‐skin” electronics.
Publisher: Elsevier BV
Date: 09-2021
Publisher: SPIE
Date: 07-06-2002
DOI: 10.1117/12.469773
Publisher: Elsevier BV
Date: 10-2016
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-05-2015
Publisher: SPIE
Date: 22-05-2001
DOI: 10.1117/12.426754
Publisher: Elsevier BV
Date: 07-2018
Publisher: Wiley
Date: 14-06-2016
DOI: 10.1111/JDV.13699
Abstract: Actinic keratosis (AK) usually co-exists in areas of severe photodamage, but the clinical applicability of reflectance confocal microscopy (RCM) in diagnosing AK currently depends on a set of parameters yet to be defined in comparison to photodamaged skin (PD). To correlate the RCM features of PD and AK with histopathology. Twenty participants with a mean age of 64 years and skin phototype I and II were studied. RCM was performed on two PD and one AK within a field of 25 cm A total of 57/60 areas were included. There were 43/57 (75%) and 14/57 (25%) histopathologically confirmed PD and AK respectively. In idual corneocytes, stratum corneum disruption, dermal inflammatory cells, increased vascularity/dilated vessels and solar elastosis were detected in PD and AK upon histopathology and RCM. The features in favour of AK were parakeratosis, hyperkeratosis, more severe keratinocyte pleomorphism and architectural disruption, and the presence of epidermal inflammatory cells. PD also demonstrated keratinocyte pleomorphism and architectural disruption though this was generally less severe than AK. A small subset of PD exhibited a comparable degree of keratinocyte pleomorphism and architectural disruption to the AKs in the cohort. The viable epidermis demonstrates PD and AK to be part of a disease continuum corresponding to field cancerization. In idual corneocytes, stratum corneum disruption, dermal inflammatory cells, increased vascularity/dilated vessels and solar elastosis may be present in PD whereas, parakeratosis and hyperkeratosis may represent the key to distinguishing AK from PD using RCM. The significance of epidermal inflammatory cells in the RCM diagnosis of AK remains to be elucidated.
Publisher: Wiley
Date: 14-08-2015
DOI: 10.1111/JDV.13215
Abstract: Actinic Keratosis (AK) is the clinical manifestation of cutaneous dysplasia of epidermal keratinocytes, with progressive trend towards squamous cell carcinoma. To evaluate the strength of the correlation between keratinocyte atypia, as detected by Reflectance Confocal Microscopy (RCM) and histopathology, and to develop a more objective atypia grading scale for RCM quantification, through a discrete ranking. A total of 48 AKs and two control areas (photodamaged and non-photodamaged skin) were selected for this study. All these areas were documented by RCM and biopsied for histopathology. One representative image of the epidermis was selected for RCM and for histopathology and used for side-by-side comparison with purpose written software. The assessor chose which of two images displayed more keratinocyte atypia, and an ordered list from the image showing the least to the most keratinocyte atypia was generated. Three evaluations were obtained for RCM and two for histopathology. Good interobserver correlation was obtained for RCM and histopathology grading, with high concordance between RCM and histopathology grading. Expert rater scan consistently distinguish different grades of cytological atypia. Non-invasive RCM data from in vivo imaging can be graded for keratinocyte atypia, comparable to histopathological grading.
Publisher: Elsevier BV
Date: 10-2018
Publisher: SPIE
Date: 27-04-2016
DOI: 10.1117/12.2227449
Publisher: Elsevier
Date: 2017
Publisher: Wiley
Date: 12-2021
DOI: 10.1111/ICS.12749
Abstract: Microneedle or fractional laser applications are the most common topical delivery enhancement platforms. However, these methods of drug delivery are not skin strata specific. Drug delivery approaches which could target specific stratum of the skin remains a challenge. Elongated microparticles (EMPs) have been used in enhancing drug delivery into the skin. The aim of this study was to evaluate, for the first time, elongated silica microparticles with two different length profiles to enhance delivery of hyaluronic acid into different strata of human skin. Two types of EMPs—long (milled EMPs) or short (etched EMPs) length ranges were characterized. A prototypical liquid formulation (Fluorescent hyaluronic acid) with and without EMP enhancement were evaluated for hyaluronic acid delivery in ex‐vivo human skin. High performance liquid chromatography, Typhoon fluorescence scanning system, laser scanning confocal microscopy and reflectance confocal microscopy (RCM) were used to validate F‐HA stability, visualize fluorescein in the skin, image the depth of F‐HA delivery in the skin and define EMP penetration in skin strata, respectively. Statistical analysis was conducted using GraphPad Prism 6 software (GraphPad Software Inc, USA). Fluorescein‐hyaluronic acid was stable and EMP enhanced skin penetration. RCM revealed that ‘etched EMP’ penetrated the skin to the stratum spinosum level. The vast majority (97.8% p 0.001) of the etched EMP did not penetrate completely through the viable epidermis and no obvious penetration into the dermis. In contrast, milled EMP showed 41‐fold increase in penetration compared to the etched EMP but penetrated beyond the dermoepidermal junction. EMPs can enhance delivery of hyaluronic acid. Using EMPs with defined length distributions, which can be tuned for a specific stratum of the skin, can achieve targeted hyaluronic acid delivery.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Public Library of Science (PLoS)
Date: 23-10-2014
Publisher: Oxford University Press (OUP)
Date: 11-2016
Publisher: Wiley
Date: 07-12-2011
Publisher: Elsevier BV
Date: 05-2015
Publisher: SPIE
Date: 19-04-2017
DOI: 10.1117/12.2256642
Publisher: PeerJ
Date: 21-08-2017
DOI: 10.7717/PEERJ.3631
Abstract: Identification of appropriate reference genes (RGs) is critical to accurate data interpretation in quantitative real-time PCR (qPCR) experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq) to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes that are consistently expressed across all s les. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as qPCR RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.
Publisher: Elsevier BV
Date: 09-2017
Publisher: IEEE
Date: 02-2008
Publisher: Springer Berlin Heidelberg
Date: 2015
Publisher: Public Library of Science (PLoS)
Date: 23-01-2015
Publisher: Springer Berlin Heidelberg
Date: 2017
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.EJPB.2013.01.020
Abstract: The use of nanoparticulate zinc oxide (ZnO-NP) in sunscreens and other cosmetic products has raised public health concerns. The two key issues are the extent of exposure to ZnO-NP and the likely hazard after the application of ZnO-NP in sunscreen and cosmetic products to humans in vivo. Our aims were to assess exposure by the extent of ZnO-NP penetration into the viable epidermis and hazard by changes in the viable epidermal redox state for a number of topical products. Of particular interest is the role of the particle coating, formulation used, and the presence of any enhancers. Multiphoton tomography with fluorescence lifetime imaging microscopy (MPT-FLIM) was used to simultaneously observe ZnO-NP penetration and potential metabolic changes within the viable epidermis of human volunteers after topical application of various ZnO-NP products. Coated and uncoated ZnO-NP remained in the superficial layers of the SC and in the skin furrows. We observed limited penetration of coated ZnO-NP dispersed in a water-in-oil emulsion formulation, which was predominantly localized adjacent to the skin furrow. However, the presence of ZnO-NP in the viable epidermis did not alter the metabolic state or morphology of the cells. In summary, our data suggest that some limited penetration of coated and uncoated ZnO-NP may occur into viable stratum granulosum epidermis adjacent to furrows, but that the extent is not sufficient to affect the redox state of those viable cells.
Publisher: Wiley
Date: 22-10-2021
DOI: 10.1111/SRT.12971
Publisher: Oxford University Press (OUP)
Date: 11-2015
Publisher: Informa UK Limited
Date: 09-2018
DOI: 10.2147/CMAR.S178768
Publisher: American Medical Association (AMA)
Date: 10-12-2021
Publisher: Elsevier BV
Date: 05-2015
Publisher: Informa UK Limited
Date: 26-11-2009
DOI: 10.1517/17425240903304032
Abstract: Since the 1990s, RNA interference (RNAi) has become a major subject of interest, not only as a tool for biological research, but also, more importantly, as a therapeutic approach for gene-related diseases. The use of short-interfering RNAs (siRNAs) for the sequence-specific knockdown of disease-causing genes has led to numerous preclinical and even a few clinical studies. Applications for cutaneous delivery of therapeutic siRNA are now emerging owing to a strong demand for effective treatments of various cutaneous disorders. Although successful studies have been performed using several different delivery techniques, most of these techniques encounter limitations for translation to the clinic with regards to patient compliance. This review describes the principal findings and applications in cutaneous RNAi therapy and focuses on the promises and pitfalls of the delivery systems.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.BIOMATERIALS.2010.02.022
Abstract: If skin's non-linear viscoelastic properties are mechanically exploited for precise antigen placement, there is tremendous promise for improved vaccines. To achieve this, we designed a Nanopatch-densely packed micro-nanoprojections (>20,000/cm(2)) to directly deposit antigen to large numbers of epidermal Langerhans cells and dermal dendritic cells. Here, we controllably applied our Nanopatches with discrete conditions between peak strain rates of approximately 100 s(-1)-7000 s(-1) and quantified resulting penetration depths, delivery payloads and skin mechanics. Increasing the strain rate of application, we overcame key skin variability, achieving increases in both projection penetration depth (by over 50% length) and area coverage of a full array (from 50% to 100%). This delivery depth precision opens the way for more fully utilizing the skin's immune function. Furthermore, we yielded new insights on mechanical behaviour of skin, including: 1) internal skin property changes that could affect/facilitate penetration 2) projection design to dictate penetration depth 3) puncture mechanics of skin in this strain rate range. Indeed, we show delivery of a model vaccine using our tested range of strain rates achieved functionally relevant tunable systemic antibody generation in mice. These findings could be of great utility in extending skin strata vaccine targeting approaches to human use.
Publisher: Mattioli1885
Date: 29-10-2021
DOI: 10.5826/DPC.1104A94
Abstract: Introduction. The differential diagnosis of lesions excised to exclude melanoma include a variety of benign and malignant melanocytic and non-melanocytic lesions. Objectives. We examined the variability between pathologists in diagnosing non-melanocytic lesions. Methods. As part of a larger study prospectively examining the diagnosis of lesions excised to exclude melanoma in 198 patients at a primary care skin cancer clinic in Newcastle, Australia, we compared diagnosis made by 5 experienced dermatopathologists, of 44 non-melanocytic lesions in 44 patients aged 22-90. Results. Forty-four lesions (out of 217 in total) were non-melanocytic. Among the 5 pathologists who examined each case there was marked variability in the terminology used to diagnose each case. The most common variability was found between seborrheic keratosis, large cell acanthoma, solar lentigo, and lichenoid keratosis. The diagnosis made by the majority of the pathologists was deemed to be the reference diagnosis. Versus majority diagnosis, 4% of benign lesions were considered malignant, and 7% of malignant diagnoses were considered as benign. Conclusions. The different terminology adopted and lack of consensus in the diagnosis of these non-melanocytic lesions in this setting suggests that training AI systems using gold standards may be problematic. We propose a new management classification scheme called MOLEM (Management of Lesions Excised to exclude Melanoma) which expands the previously described MPATH-dx to include non-melanocytic lesions.
Publisher: SPIE-Intl Soc Optical Eng
Date: 2010
DOI: 10.1117/1.3466580
Abstract: Ex vivo human skin has been used extensively for cosmeceutical and drug delivery studies, transplantable skin allografts, or skin flaps. However, it has a half-life of a few days due to ischemic necrosis. Traditional methods of assessing viability can be time-consuming and provide limited metabolic information. Using multiphoton tomography and fluorescence lifetime imaging (MPT-FLIM) we assess ischemic necrosis of ex vivo skin by NAD(P)H autofluorescence intensity and fluorescence lifetime. Ex vivo skin is stored in the presence and absence of nutrient media (Dulbecco Modified Eagle Medium) at -20, 4, and 37 degrees C and room temperature over a 7-day time course to establish different rates of metabolic deterioration. At higher temperatures we observe a decrease in NAD(P)H autofluorescence, higher image noise, and a significant increase in the average fluorescence lifetime (tau(m)) from approximately 1000 to 2000 ps. Additionally, significant distortions in NAD(P)H fluorescence lifetime histograms correspond to the reduction in autofluorescence. Skin kept at 4 degrees C, with or without media, showed the least change. Our findings suggest that MPT-FLIM enables useful noninvasive optical biopsies to monitor the metabolic state and deterioration of human skin for research and clinical purposes.
Publisher: Future Medicine Ltd
Date: 09-2013
DOI: 10.2217/FON.13.88
Publisher: Elsevier BV
Date: 05-2014
Publisher: American Astronomical Society
Date: 19-12-2016
Publisher: Elsevier BV
Date: 2020
Publisher: Elsevier BV
Date: 05-2017
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2016
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.ADDR.2011.01.012
Abstract: Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300 nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles >10nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored.
Publisher: Wiley
Date: 25-07-2007
DOI: 10.1002/DVDY.21231
Publisher: Wiley
Date: 15-11-2014
Publisher: Wiley
Date: 07-06-2012
DOI: 10.1111/J.1600-0846.2012.00640.X
Abstract: 5-Aminolevulinate (ALA) is an important photodynamic therapy drug for the treatment of actinic keratoses and other non-melanoma skin cancers in cosmetically sensitive areas. One limitation of this drug is a relatively high recurrence rate. Our aim was to evaluate the feasibility of ultrasound augmented ALA delivery in excised human skin. An ultrasonic delivery device was used to enhance radiolabelled ALA into excised skin. Quantification of ALA was performed after passive and ultrasonic ALA delivery. Transepidermal water loss was used as a measure of barrier function before and after ultrasonic treatment. We found that ultrasonic treatment dramatically increased the mean cumulative amount of ALA to P< 0.0001 from 4 to 8 h when compared to passive ALA treatment. The flux was calculated to be 54.8 ± 8.0 μg/cm(2) h with ultrasound treatment. TEWL increased nearly two-fold, from 12.3 to 21.0, after ultrasound treatment. Our study supports the use of ultrasound for improved ALA delivery by showing significant improvements in the cumulative drug load and flux via combined ultrasound and ALA treatment.
Publisher: Bentham Science Publishers Ltd.
Date: 18-10-2016
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 26-05-2014
DOI: 10.1111/ADJ.12174
Abstract: The prevalence of oral and maxillofacial pathology has not previously been reported in the Australian paediatric population. This study aimed to audit a large pathology service to provide insight into the prevalence of oral and maxillofacial pathology. Written records of a major Australian oral pathology service were imported into an electronic database. Age, gender and histological diagnosis were assessed. Prevalence of histological diagnoses as a percentage of the major diagnostic categories and of the whole s le were calculated, as well as gender predilections and mean age of presentation of disease. A total of 1305 oral pathology specimens, collected from paediatric patients aged 16 and under were included in the analysis. The most common pathology was dental pathology (24.4%), followed by odontogenic cysts (18.5%) and mucosal pathology (17.0%). The most frequently encountered lesion was the dentigerous cyst (9.4%), followed by fibrous hyperplasia (8.3%), radicular cyst (5.2%) and chronic periapical granuloma (5.2%). In the paediatric population, dental pathology and specifically, the dentigerous cyst is the most common pathology type sent for histopathology, suggesting a high prevalence of pathology of dental origin occurring in Australian children.
Publisher: MDPI AG
Date: 09-2016
DOI: 10.3390/S16091411
Publisher: IEEE
Date: 02-2008
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.EXER.2005.09.025
Abstract: The purpose of this study was to culture and characterize endothelial cells and angioblasts, vascular precursors, from adult and neonatal dog retina and determine if angioblasts are committed to endothelial cell lineage or have the potential to be multipotent, i.e. express phenotypic characteristics of other vascular cell types. Endothelial cells were established from adult dog retina (ADREC) by the technique of Gitlin and D'Amore. For angioblasts, pieces of neonatal day 2 (P2) avascular peripheral retina were placed under coverslips until sufficient cells had explanted. All cells were maintained initially on hyaluronic acid (HA)/fibronectin (FN) substratum. Neonatal canine retinal angioblasts (NCRA) were maintained initially on retinal-derived growth factor with alpha-amino adipic acid to inhibit growth of Muller cells. Cell lines were characterized by enzyme histochemistry [menadione-dependent alpha glycerophosphate dehydrogenase (alphaGPDH), marker for angioblasts] and immunocytochemistry. Once characterized, cells were grown on FN, or collagens I or IV substrata and fed platelet-derived growth factor-BB (PDGF-BB) or fibroblast growth factor-2 (FGF-2). The phenotypic expression of a marker for endothelial cells [acetylated LDL (acLDL) uptake] or a marker for pericytes and smooth muscle cells, production of alpha smooth muscle actin (alphaSMA), was evaluated under those conditions. The canine retinal cell lines that were established had the following characteristics when maintained on serum and a retinal extract. Angioblasts had low expression of vWf and VEGF-R2 (two markers for canine endothelial cells), and very low uptake of acLDL but high expression of alphaGPDH and adenosine A2a receptors (A2aR) (two markers for canine angioblasts in vivo). ADREC had high expression of endothelial cell markers (vWf, VEGF-R2, and acLDL uptake) but minimal expression of alphaGPDH and A2aR. Both angioblasts and endothelial cells expressed CXCR4, a marker for hemangioblasts. Angioblasts grown on any of the substrata in the presence of FGF-2 had high uptake of acLDL and low expression of alphaSMA, while those grown in the presence of PDGF-BB had high expression of alphaSMA and low uptake of acLDL. In conclusion, angioblasts cultured from peripheral vascular retina have low expression of endothelial cell markers and high alphaGPDH and A2aR, markers for canine angioblasts in vivo. Angioblasts will internalize acLDL when maintained on FGF-2 and express alphaSMA when maintained on PDGF-BB, suggesting that they have the potential to become endothelial cells or pericytes, i.e. are multipotent.
Publisher: Science Impact, Ltd.
Date: 09-2017
Publisher: MDPI AG
Date: 20-07-2015
Publisher: Elsevier
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 08-2004
DOI: 10.1007/S10735-004-2196-4
Abstract: Complex, multilayered nanoparticles hold great promise for more sophisticated drug/gene delivery systems to single cells. Outermost layers can include cell targeting and cell-entry facilitating molecules. The next layer can include intracellular targeting molecules for precise delivery of the nanoparticle complex inside the cell of interest. Molecular biosensors can be used to confirm the presence of expected molecules (for ex le, reactive oxygen species (ROS) as a surrogate molecule for signs of infection, or for activation in radiation damage, etc.) prior to delivery of counter-measure molecules such as drugs or gene therapy. They can also be used as a feedback control mechanism to control the proper amount of drug/gene delivery for each cell. Importantly, the full nanoparticle system can be used to prevent any cells from encountering the drug unless that cell is specifically targeted. Thus, if a cell is initially non-specifically targeted, a secondary check for other molecular targets which must also be present inside the target cell of interest can be used to catch initial targeting mistakes and prevent subsequent delivery of treatment molecules to the wrong cells. The precise intracellular location of nanoparticles within specific regions of a cell can be confirmed by 3D multispectral confocal microscopy. These single cell molecular morphology measurements can be extended from in idual cells, to other cells in a tissue in tissue monolayers or tissue sections.
Publisher: Wiley
Date: 26-07-2021
DOI: 10.1111/ICS.12720
Abstract: Evaluation of skin ageing is a non‐standardized, subjective process, with typical measures relying coarse, qualitatively defined features. Reflectance confocal microscopy depth stacks contain indicators of both chrono‐ageing and photo‐ageing. We hypothesize that an ageing scale could be constructed using machine learning and image analysis, creating a data‐driven quantification of skin ageing without human assessment. En‐face sections of reflectance confocal microscopy depth stacks from the dorsal and volar forearm of 74 participants (36/18/20 training/testing/validation) were represented using a histogram of visual features learned using unsupervised clustering of small image patches. A logistic regression classifier was trained on these histograms to differentiate between stacks from 20‐ to 30‐year‐old and 50‐ to 70‐year‐old volunteers. The probabilistic output of the logistic regression was used as the fine‐grained ageing score for that stack in the testing set ranging from 0 to 1. Evaluation was performed in two ways: on the test set, the AUC was collected for the binary classification problem as well as by statistical comparison of the scores for age and body site groups. Final validation was performed by assessing the accuracy of the ageing score measurement on 20 depth stacks not used for training or evaluating the classifier. The classifier effectively differentiated stacks from age groups with a test set AUC of 0.908. Mean scores were significantly different when comparing age groups (mean 0.70 vs. 0.44 t = −6.62, p = 0.0000) and also when comparing stacks from dorsal and volar body sites (mean 0.64 vs. 0.53 t = 3.12, p = 0.0062). On the final validation set, 17 out of 20 depth stacks were correctly labelled. Despite being limited to only coarse training information in the form of ex le stacks from two age groups, the trained classifier was still able to effectively discriminate between younger skin and older skin. Curiously, despite being only trained with chronological age, there was still evidence for measurable differences in age scores due to sun exposure—with marked differences in scores on sun‐exposed dorsal sites of some volunteers compared with less sun‐exposed volar sites. These results suggest that fine‐grained data‐driven quantification of skin ageing is achievable.
Publisher: Wiley
Date: 15-03-2007
DOI: 10.1002/DVDY.21122
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.OTSR.2014.03.022
Abstract: The pathogenesis of full-thickness tears of the rotator cuff remains unclear. Apart from age and trauma, distinct scapular morphologies have been found to be associated with rotator cuff disease. The purpose of the present study was to evaluate whether a score formed using these established risk factors was able to predict the presence of a rotator cuff tear reliably. We retrospectively assessed a consecutive series of patients with a minimal age of 40 years old, who had true antero-posterior (AP) radiographs of their shoulders, as well as a magnetic resonance (MR) gadolinium-arthrography, between January and December 2011. In all of these patients, the critical shoulder angle (CSA) was determined, and MR images were assessed for the presence of rotator cuff tears. Additionally, the patients' charts were reviewed to obtain details of symptom onset. Based on these factors, the so-called rotator cuff tear (RCT) score was calculated. Patients with full-thickness RCTs were significantly older and had significantly larger CSAs than patients with intact rotator cuffs. Multiple logistic regression, using trauma, age and CSA as independent variables, revealed areas under the curve (AUCs) for trauma of 0.55, for age of 0.65 and for CSA of 0.86. The combination of all three factors was the most powerful predictor, with an AUC of 0.92. Age, trauma and the CSA can accurately predict the presence of a posterosuperior RCT. Level IV. Case series with no comparison groups.
Publisher: Medical Journals Sweden AB
Date: 2015
Publisher: Oxford University Press (OUP)
Date: 20-06-2012
DOI: 10.1111/J.1365-2133.2012.10943.X
Abstract: Skin ageing is a complex process due to intrinsic chronological factors (chronoageing) and extrinsic environmental factors. The primary extrinsic factor is cumulative ultraviolet (UV) exposure, and is therefore termed photoageing. The current standards for measuring cumulative sun damage are biopsy histology and skin microtopography. However, skin biopsies are too invasive for population studies and skin replicas render only superficial skin architecture data. Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that allows for in vivo imaging of the skin at quasihistological resolution. To define and identify RCM features associated with chronological ageing and photoageing on the forearm in two age groups with different skin phototypes and to assess whether these results agree with previous findings. We obtained RCM images of dorsal and volar nonlesional skin of the lower forearm of 75 in iduals with skin Fitzpatrick phototypes I-III in two age groups (20-30 years and 50-60 years). From each participant and body site, 21 RCM features were assessed and statistically significant differences between the two age groups and different forearm sites determined. RCM enabled identification of changes in architecture, cell morphology and extracellular matrix (collagen) at the level of the epidermis, dermoepidermal junction and papillary dermis. Changes that were correlated with chronological ageing and which were aggravated on the UV-exposed dorsal forearm were: loss of small skin furrows resulting in wider and less intersecting furrows irregularity of the epidermal honeycomb pattern irregularly distributed (mottled) pigmented keratinocytes/melanocytes irregularity of the papillary rings and/or effacement of the rete ridges and loss of thin collagen fibres and presence of collagen clods. We have tested previously reported and new parameters for skin ageing evaluation by RCM, and identified 15 statistically significant RCM features that can be used to quantify ageing and photoageing in forearm skin noninvasively.
Publisher: The Optical Society
Date: 17-10-2014
DOI: 10.1364/BOE.5.003981
Publisher: Wiley
Date: 29-11-2017
DOI: 10.1002/LSM.22758
Abstract: Ablative fractional laser (AFXL) is an acknowledged technique to increase uptake of topical agents in skin. Micro thermal ablation zones (MAZs) consist of ablated vertical channels surrounded by a coagulation zone (CZ). Laser scanning confocal microscopy (LSCM) images in idual MAZs at 733 nm (reflectance confocal microscopy (RCM)). Further, LSCM can image sodium fluorescein (NaF) fluorescence with 488 nm excitation (fluorescence confocal microcopy (FCM)), a small hydrophilic test molecule (370 MW, log P -1.52), which may simulate uptake, bio-distribution and kinetics of small hydrophilic drugs. To explore LSCM for combined investigations of CZ thickness and uptake, bio-distribution and kinetics of NaF in AFXL-exposed skin. Excised human abdominal skin s les were exposed to AFXL (15 mJ/microbeam, 2% density) and NaF gel (1000 μg/ml, 10 μl/cm2) in six repetitions, including untreated control s les. CZ thickness and spatiotemporal fluorescence intensities (FI) were quantified up to four hours after NaF application by RCM and FCM. Test sites were scanned to a depth of 200 μm, quantifying thickness of skin compartments (stratum corneum, epidermis, upper dermis), in idual CZ thicknesses and FI in CZ and surrounding skin. RCM images established skin morphology to a depth of 200 μm. The CZ thickness measurements were feasible to a depth of 50 μm, and remained unchanged over time at 50 μm (P > 0.5). FI were detected to a depth of 160 μm and remained constant in CZ up to four hours after NaF application (15 minutes: 79 AU (73-92 AU), 60 minutes: 72 AU (58-82 AU), four hours: 78 AU (71-90 AU), P > 0.1). In surrounding skin, FI increased significantly over time, but remained lower than FI in CZ (15 minutes: 21 AU (17-22 AU), 60 minutes: 21 AU (19-26 AU), four hours: 42 (31- 48 AU), P = 0.03). AFXL-processed skin generated higher FI compared to non-laser processed skin in epidermis and upper dermis at 60 minutes and four hours (P = 0.03). By LSCM, assessment of the AFXL-induced CZ thickness was feasible to a depth of 50 μm, and assessment of FI from a small hydrophilic test molecule, NaF in CZ and surrounding skin feasible to a depth of 160 μm. Lasers Surg. Med. 50:70-77, 2018. © 2017 Wiley Periodicals, Inc.
Publisher: American Medical Association (AMA)
Date: 04-2017
Publisher: Future Medicine Ltd
Date: 04-2012
DOI: 10.2217/NNM.11.149
Abstract: Aims: To date, the description of a single, suitable method to observe in detail metal oxide nanoparticles in situ within sunscreens is currently lacking, despite growing concern as to how they interact with humans. This study explores the usefulness of transmission electron microscopy to characterize the nanoparticles in sunscreens. Materials & methods: High-pressure freezing then freeze substitution was used to prepare resin-embedded commercial sunscreen s les, and ultrathin sections of these were observed with transmission electron microscopy. Conventional room temperature processing for resin embedding was also trialed. Results: High-pressure frozen/freeze substituted s les provided clear visualization of the size and shape of the nanoparticles and agglomerates and allowed further characterization of the composition and crystal form of the metal oxides, while conventionally processed chemically fixed s les were subject to distribution/agglomeration artifacts. Conclusion: Transmission electron microscopy of high-pressure frozen/freeze substituted s les is an ideal method to completely observe metal oxide nanoparticles in situ in sunscreens.
Publisher: Humana Press
Date: 2013
DOI: 10.1007/978-1-62703-475-3_1
Abstract: Noninvasive detection of biological responses to reactive oxygen species (ROS) in vivo could shed light on mechanisms at work in erse areas like developmental dynamics, therapeutic effectiveness, drug discovery, pathogenic processes, and disease prevention. Research on ROS is usually dependent on in vitro models without translational relevance. Nanoscale (<100 nm) particulates are attractive carriers and platforms for biosensor technology due to their small size, flexible assembly, and favorable toxicity profiles. Intracellular signalling pathways activated in response to ROS have been well documented and mechanisms elaborated. Likewise, there is a wealth of genetic reporter systems that utilize fluorescent proteins capable of being monitored noninvasively. We combined these elements into a platform technology that utilizes nanoparticle-tethered synthetic genetic elements that respond to cellular response elements to report endogenous responses to oxidative insult through fluorescent gene expression. We envision the future of this technology to play a research role quantifying oxidative stress in vivo and a future clinical role as an automated theragnostic for ROS-related diseases. The production of this nanobiosensor technology utilizes off-the-shelf components and can be carried out in a molecular biology laboratory. Assessment of fluorescent protein expression can be done with noninvasive imaging and quantitative protein expression analysis. This is a flexible nanoparticle-based reporter system for monitoring in vivo responses to ROS.
Publisher: Springer Science and Business Media LLC
Date: 30-06-2011
DOI: 10.1007/S11095-011-0515-5
Abstract: There is a lack of relevant, non-animal alternatives for assessing exposure and toxicity of nanoparticle-containing cosmetics, e.g. sunscreens. Our goal was to evaluate timecorrelated single photon counting (TCSPC) for simultaneous monitoring of zinc oxide nanoparticles (ZnO-NP) and the metabolic state of volunteer skin. We separated the fluorescence lifetime signatures of endogenous fluorophore signals (i.e. nicotinamide adenine dinucleotide phosphate, NAD(P)H and keratin) and the ZnO-NP signal using advanced TCSPC to simultaneously determine ZnO-NP penetration profiles and NAD(P)H changes in subjects with altered barrier function, including tape-stripped skin and in psoriasis or atopic dermatitis lesions. We detected no ZnO-NP penetration into viable human skin in any group. ZnO-NP signal was significantly increased (p < 0.01) on the surface of tape-stripped and lesional skin after 4 and 2 h of treatment, respectively. Free NAD(P)H signal significantly increased in tape-stripped viable epidermis treated for 4 h of ZnO-NP compared to vehicle control. No significant NAD(P)H changes were noted in the lesional study. TCSPC techniques enabled simultaneous, real-time quantification of ZnO-NP concentration and NAD(P)H via non-invasive imaging in the stratum corneum and viable epidermis of volunteers.
Publisher: Wiley
Date: 12-08-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-05-2019
Abstract: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types. To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma. Patients received a single intravenous dose of tozuleristide 3 to 29 h before surgery. Fluorescence images of tumor and cavity in Situ before and after resection and of excised tissue ex Vivo were acquired, along with safety and pharmacokinetic measures. A total of 17 subjects received doses between 3 and 30 mg. No dose-limiting toxicity was observed, and no reported adverse events were considered related to tozuleristide. At doses of 9 mg and above, the terminal serum half-life for tozuleristide was approximately 30 min. Fluorescence signal was detected in both high- and low-grade glial tumors, with high-grade tumors generally showing greater fluorescence intensity compared to lower grade tumors. In high-grade tumors, signal intensity increased with increased dose levels of tozuleristide, regardless of the time of dosing relative to surgery. These results support the safety of tozuleristide at doses up to 30 mg and suggest that tozuleristide imaging may be useful for FGS of gliomas.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.EJPB.2010.12.023
Abstract: New multiphoton and confocal microscope technologies and fluorescence lifetime imaging techniques are now being used to non-invasively image, in space (three dimensions),in time, in spectra, in lifetime and in fluorescence anisotropy (total of 7 dimensions), fluorescent molecules in in situ and in vivo biological tissue, including skin. The process involves scanning a 2D area and measuring fluorescence at a given tissue depth below the surface after excitation by a laser beam with a wavelength within the one-photon or two-photon absorption band of the fluorophores followed by the stacking together of a series of 2D images from different depths to reconstruct the full spatial structure of the s le. Our aim in this work is to describe the principles, opportunities, limitations and applications of this new technology and its application in defining skin morphology, disease and skin penetration in vitro and in vivo by drugs, chemicals and nanoparticles. A key emphasis is in the use of fluorescence lifetime imaging to add additional specificity and quantitation to the detection of the various exogenous chemicals and nanoparticles that may be applied to the skin as well as endogenous fluorescent species in the skin. Ex les given include equipment configuration components in skin autofluorescence in various skin strata imaging and quantification of coexisting drugs and their metabolites skin pH nanoparticle zinc oxide skin penetration liposome delivery of drugs to deeper tissues and observations in skin ageing and in various skin diseases.
Publisher: Elsevier BV
Date: 05-2015
Publisher: Elsevier
Date: 2014
Publisher: SPIE
Date: 04-2005
DOI: 10.1117/12.589422
Publisher: American Medical Association (AMA)
Date: 09-2013
Publisher: Wiley
Date: 22-01-2023
DOI: 10.1002/SKI2.216
Abstract: Skin cancer represents a significant health burden across the globe and early detection is critical to improve health outcomes. Three‐dimensional (3D) total‐body photography is a new and emerging technology which can support clinicians when they monitor people's skin over time. The aim of this study was to improve our understanding of the epidemiology and natural history of melanocytic naevi in adults, and their relationship with melanoma and other skin cancers. Mind Your Moles was a 3‐year prospective, population‐based cohort study which ran from December 2016 to February 2020. Participants visited the Princess Alexandra Hospital every 6 months for 3 years to undergo both a clinical skin examination and 3D total‐body photography. A total of 1213 skin screening imaging sessions were completed. Fifty‐six percent of participants ( n = 108/193) received a referral to their own doctor for 250 lesions of concern, 101/108 (94%) for an excision/biopsy. Of those, 86 people (85%) visited their doctor and received an excision/biopsy for 138 lesions. Histopathology of these lesions found 39 non‐melanoma skin cancers (across 32 participants) and six in situ melanomas (across four participants). 3D total‐body imaging results in diagnosis of a high number of keratinocyte cancers (KCs) and their precursors in the general population.
Publisher: Wiley
Date: 12-09-2012
DOI: 10.1002/WNAN.1189
Abstract: Multiphoton microscopy is being used as a tool for tracking nanoparticles and assessing endogenous autofluorescent molecules. This technology is founded on femtosecond lasers that are capable of exciting unlabeled metal nanoparticles, quantum dots, and upconverting nanoparticles. The addition of time-correlated single-photon counting detectors enables fluorescence lifetime imaging. Fluorescence lifetime measurements result in high-resolution, quantitative data that can be used to distinguish nanoparticle signals from those of endogenous fluorophores. This application of multiphoton microscopy is capable of simultaneous nanoparticle and NAD(P)H imaging, resulting in the capacity for dye-free assessments of treatment-induced metabolic changes. The stage is set for advanced, clinical imaging focused nanoparticle trials that can directly address critical issues in nanomedicine and nanotoxicology.
Publisher: Elsevier BV
Date: 02-2008
Publisher: Elsevier BV
Date: 10-2016
Publisher: SPIE
Date: 08-12-2016
DOI: 10.1117/12.2250621
Publisher: S. Karger AG
Date: 18-12-2014
DOI: 10.1159/000366540
Abstract: Clinical assessment of actinic keratosis is known to be a variable process however, there are currently no non-invasive alternatives for objectively assessing the condition besides excision and histopathology. While a number of technologies for examining potential actinic keratoses are under development, each of these still requires subjective human assessment. The existing approaches focus on assessing colour and texture features in clinical-scale images, such as those from dermoscopy and digital photography, and on structural or cellular characteristics in cellular-scale images, such as those from multiphoton microscopy and reflectance confocal microscopy. The future of actinic keratosis management is likely to be a combination of analysing regional photography to determine potential lesion locations and analysis of the structural and cellular features by reflectance confocal microscopy for an in vivo pathology diagnosis.
Publisher: S. Karger AG
Date: 18-12-2014
DOI: 10.1159/000366541
Abstract: Actinic keratosis is a common result of severe sun damage and is usually present on sun-exposed skin. Reflectance confocal microscopy is a non-invasive clinical imaging modality that results in quasi-histological, en face skin images. In this chapter, we review the available literature and distill the common features of actinic keratosis, as seen by reflectance confocal microscopy. Finally, several ex les are discussed in the context of matching clinical, histopathological and reflectance confocal microscopy images. Of all of the morphological features of actinic keratoses, the epidermal honeycomb pattern is the most telling when viewing the lesions using reflectance confocal microscopy. In the near future, we expect the definition of consensus criteria for diagnosing actinic keratoses and differentiating this precursor lesion.
Publisher: BMJ
Date: 09-2018
DOI: 10.1136/BMJOPEN-2018-025857
Abstract: Having many melanocytic naevi or ‘moles’ on the skin is the strongest predictor of melanoma thus, much can be learnt from investigating naevi in the general population. We aim to improve the understanding of the epidemiology and biology of naevi by conducting a 3-year prospective study of melanocytic naevi in adults. This is a population-based cohort study of melanocytic naevi in 200 adults aged 20–69 years recruited via the Australian electoral roll. At baseline, participants will complete a questionnaire on their sun behaviour and health and undergo a clinical examination. Three-dimensional (3D) total-body photography will be used to record the images of skin lesions. Pigmented naevi will be analysed in terms of number, diameter, colour and border irregularity using automated analysis software (excluding scalp, beneath underwear and soles of feet). All naevi ≥5 mm will be recorded using the integrated dermoscopy photographic system. A saliva s le will be obtained at baseline for genomic DNA analysis of pigmentation, naevus and melanoma-associated genes using the Illumina HumanCoreExome platform. The sun behaviour and health follow-up questionnaire, clinical examination and 3D total-body photography will be repeated every 6 months for 3 years. The first 50 participants will also undergo manual counts of naevi ≥2 mm and ≥5 mm at baseline, 6-month and 12-month follow-ups. Microbiopsy and excision of naevi of research interest is planned to commence at the 18-month time point among those who agree to donate s les for detailed histopathological and molecular assessment. This study was approved by the Metro South Health Human Research Ethics Committee in April 2016 (approval number: HREC/16/QPAH/125). The findings will be disseminated through peer-reviewed and non-peer-reviewed publications and presentations at conferences.
Publisher: SPIE-Intl Soc Optical Eng
Date: 27-11-2013
Publisher: Wiley
Date: 17-06-2010
DOI: 10.1002/WNAN.65
Abstract: What do nanoparticles offer drug delivery to the eye that traditional formulations do not? The underlying concept of nanomedicine is that the nanomaterials have properties that their constituent components do not have. These unique properties are the benefit, but the cost can be more a complicated toxicology assessment. Ocular delivery of therapeutic nanoparticles has the potential to greatly increase the quality of life through maintaining our vision. The eye is composed of multiple tissue types, i.e., epithelium, muscle, immune cells, neural cells, and blood vessels, to name a few. Ocular diseases affect many of these tissues at once. Introduce novel therapeutic nanoparticles and determining mechanisms of toxicity becomes challenging. This review is a survey of what is known about toxicity in experimental nanoparticles for ocular therapeutics. Specific cases are chosen to illustrate a range of toxic effects of nanoparticles in the eye. There is a unique research opportunity for in-depth toxicology studies of nanoparticles in the eye. This has been made possible by the rapid development of therapeutic nanoparticles in the last few years.
Publisher: Wiley
Date: 08-02-2016
DOI: 10.1111/JDV.13548
Publisher: Oxford University Press (OUP)
Date: 07-2013
DOI: 10.1111/BJD.12408
Publisher: JMIR Publications Inc.
Date: 17-02-2022
Abstract: igital 3D total-body photography of the skin surface is an emerging imaging modality that can facilitate the identification of new and changing nevi. e aimed to describe the experiences of study participants drawn from the general population who were provided 3D total-body photography and dermoscopy for the monitoring of nevi. population-based prospective study of adults aged 20-70 years from South East Queensland, Australia was conducted. Participants underwent 3D total-body photography and dermoscopy every 6 months over a 3-year period. Participants were asked to provide closed and open-ended feedback on their 3D total-body photography and dermoscopy experience (eg, comfort, trust, intended future use, and willingness to pay) at the halfway study time point (18 months) and final study time point (36 months). We assessed changes in participants’ reported experience of 3D total-body photography, and patient characteristics associated with patient experience at the end of the study (36 months) were analyzed. total of 149 participants completed the surveys at both the 18- and 36-month time points (median age 55, range 23-70 years n=94, 63.1% were male). At the 18-month time point, most participants (n=103, 69.1%) stated they completely trusted 3D total-body imaging for the diagnosis and monitoring of their nevi, and this did not change at the 36-month (n=104, 69.8%) time point. The majority of participants reported that they were very comfortable or comfortable with the technology at both the 18- (n=138, 92.6%) and 36-month (n=140, 94%) time points, respectively albeit, the number of participants reporting that they were very comfortable reduced significantly between the 18- and 36-month time points, from 71.1% (n=106) to 61.1% (n=91 i P /i =.01). Almost all participants (n=140, 94%) would consider using this technology if it were to become commercially available, and this did not change during the two study time points. Half of the participants (n=74) cited barriers to participating in 3D total-body photography, including trust in the ability of this technology to detect and monitor suspicious lesions, digital privacy, cost, and travel requirements. he majority of participants expressed positive attitudes toward 3D total-body photography for the monitoring of their moles. Half of the participants identified potential barriers to uptake.
Publisher: Frontiers Media SA
Date: 08-09-2020
Publisher: IEEE
Date: 02-2010
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/836375
Abstract: Greenhouse gas emitted by the transport sector around the world is a serious issue of concern. To minimize such emission the automobile engineers have been working relentlessly. Researchers have been trying hard to switch fossil fuel to alternative fuels and attempting to various driving strategies to make traffic flow smooth and to reduce traffic congestion and emission of greenhouse gas. Automobile emits a massive amount of pollutants such as Carbon Monoxide (CO), hydrocarbons (HC), carbon dioxide (CO 2 ), particulate matter (PM), and oxides of nitrogen (NO x ). Intelligent transport system (ITS) technologies can be implemented to lower pollutant emissions and reduction of fuel consumption. This paper investigates the ITS techniques and technologies for the reduction of fuel consumption and minimization of the exhaust pollutant. It highlights the environmental impact of the ITS application to provide the state-of-art green solution. A case study also advocates that ITS technology reduces fuel consumption and exhaust pollutant in the urban environment.
Publisher: SPIE-Intl Soc Optical Eng
Date: 02-10-2014
Publisher: Elsevier BV
Date: 04-2010
Location: Korea, Republic of
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2013
End Date: 2015
Funder: Australian Research Council
View Funded ActivityStart Date: 2014
End Date: 2018
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2013
End Date: 03-2016
Amount: $370,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2021
End Date: 06-2022
Amount: $909,079.00
Funder: Australian Research Council
View Funded ActivityStart Date: 04-2022
End Date: 04-2025
Amount: $296,579.00
Funder: Australian Research Council
View Funded Activity