Photoacoustic imaging for cutaneous melanoma assessment: a comprehensive review.

Significance: Cutaneous melanoma (CM) has a high morbidity and mortality rate, but it can be cured if the primary lesion is detected and treated at an early stage. Imaging techniques such as photoacoustic (PA) imaging (PAI) have been studied and implemented to aid in the detection and diagnosis of CM. Aim: Provide an overview of different PAI systems and applications for the study of CM, including the determination of tumor depth/thickness, cancer-related angiogenesis, metastases to lymph nodes, circulating tumor cells (CTCs), virtual histology, and studies using exogenous contrast agents. Approach: A systematic review and classification of different PAI configurations was conducted based on their specific applications for melanoma detection. This review encompasses animal and preclinical studies, offering insights into the future potential of PAI in melanoma diagnosis in the clinic. Results: PAI holds great clinical potential as a noninvasive technique for melanoma detection and disease management. PA microscopy has predominantly been used to image and study angiogenesis surrounding tumors and provide information on tumor characteristics. Additionally, PA tomography, with its increased penetration depth, has demonstrated its ability to assess melanoma thickness. Both modalities have shown promise in detecting metastases to lymph nodes and CTCs, and an all-optical implementation has been developed to perform virtual histology analyses. Animal and human studies have successfully shown the capability of PAI to detect, visualize, classify, and stage CM. Conclusions: PAI is a promising technique for assessing the status of the skin without a surgical procedure. The capability of the modality to image microvasculature, visualize tumor boundaries, detect metastases in lymph nodes, perform fast and label-free histology, and identify CTCs could aid in the early diagnosis and classification of CM, including determination of metastatic status. In addition, it could be useful for monitoring treatment efficacy noninvasively.

Photoprotective measures among adolescents stratified by region: An analysis utilizing the National College Health Assessment.

BACKGROUND/PURPOSE: Exposure to sunlight has been shown to cause pigmentary alterations, photoaging and photocarcinogenesis. Understanding photoprotective patterns in adolescent populations is beneficial to public health initiatives. We utilized data provided by the American College Health Association's National College Health Assessment to evaluate photoprotective behaviors among adolescent populations. METHODS: Behavioral questions related to photoprotection were analyzed from the American College Health Association (ACHA) National College Health Assessment (NCHA) (Version III). RESULTS: When comparing races, Black/African American respondents had the lowest association of practicing photoprotective behaviors in comparison to white respondents (p < .05). When comparing US geographic regions, the south had the lowest association of photoprotective measures (p < .05). LIMITATIONS: The response rate of each institution varied, although there was still a large quantity of respondents. Finally, we cannot discern the specific reasoning for adolescent populations not using sunscreen. CONCLUSION: These data identify demographics where efforts to enhance education on photoprotective behaviors, specifically among skin of color and southern population, to support public health initiatives.

Sensing and regulation of reactive sulfur species (RSS) in bacteria.

The infected host deploys generalized oxidative stress caused by small inorganic reactive molecules as antibacterial weapons. An emerging consensus is that hydrogen sulfide (H2S) and forms of sulfur with sulfur-sulfur bonds termed reactive sulfur species (RSS) provide protection against oxidative stressors and antibiotics, as antioxidants. Here, we review our current understanding of RSS chemistry and its impact on bacterial physiology. We start by describing the basic chemistry of these reactive species and the experimental approaches developed to detect them in cells. We highlight the role of thiol persulfides in H2S-signaling and discuss three structural classes of ubiquitous RSS sensors that tightly regulate cellular H2S/RSS levels in bacteria, with a specific focus on the chemical specificity of these sensors.

Polysulfide metabolizing enzymes influence SqrR-mediated sulfide-induced transcription by impacting intracellular polysulfide dynamics.

Sulfide plays essential roles in controlling various physiological activities in almost all organisms. Although recent evidence has demonstrated that sulfide is endogenously generated and metabolized into polysulfides inside the cells, the relationship between polysulfide metabolism and polysulfide-sensing mechanisms is not well understood. To better define this interplay between polysulfide metabolism and sensing in cells, we investigated the role of polysulfide-metabolizing enzymes such as sulfide:quinone oxidoreductase (SQR) on the temporal dynamics of cellular polysulfide speciation and on the transcriptional regulation by the persulfide-responsive transcription factor SqrR in Rhodobacter capsulatus. We show that disruption of the sqr gene resulted in the loss of SqrR repression by exogenous sulfide at longer culture times, which impacts the speciation of intracellular polysulfides of Δsqr vs. wild-type strains. Both the attenuated response of SqrR and the change in polysulfide dynamics of the Δsqr strain is fully reversed by the addition to cells of cystine-derived polysulfides, but not by glutathione disulfide (GSSG)-derived polysulfides. Furthermore, cysteine persulfide (CysSSH) yields a higher rate of oxidation of SqrR relative to glutathione persulfide (GSSH), which leads to DNA dissociation in vitro. The oxidation of SqrR was confirmed by a mass spectrometry-based kinetic profiling strategy that showed distinct polysulfide-crosslinked products obtained with CysSSH vs. GSSH. Taken together, these results establish a novel association between the metabolism of polysulfides and the mechanisms for polysulfide sensing inside the cells.

Protocol for using organic persulfides to measure the chemical reactivity of persulfide sensors.

Hydrogen sulfide (H2S) and downstream reactive sulfur species (RSS), including organic persulfides, protect bacterial cells against diverse oxidative stressors. Specialized dithiol-based transcriptional repressors sense persulfides directly to control cellular H2S/RSS and avoid toxicity. Here, we present a protocol to quantify the kinetics of chemical reactivity of cysteines in two bacterial persulfide sensors toward cysteine persulfide and glutathione persulfide, with a LC-ESI-MS analysis that results in a kinetic model. This protocol has potential applications to other cysteine-containing proteins and oxidants. For complete details on the use and execution of this protocol, please refer to Fakhoury et al. (2021) and Capdevila et al. (2021).

Functional asymmetry and chemical reactivity of CsoR family persulfide sensors.

CstR is a persulfide-sensing member of the functionally diverse copper-sensitive operon repressor (CsoR) superfamily. While CstR regulates the bacterial response to hydrogen sulfide (H2S) and more oxidized reactive sulfur species (RSS) in Gram-positive pathogens, other dithiol-containing CsoR proteins respond to host derived Cu(I) toxicity, sometimes in the same bacterial cytoplasm, but without regulatory crosstalk in cells. It is not clear what prevents this crosstalk, nor the extent to which RSS sensors exhibit specificity over other oxidants. Here, we report a sequence similarity network (SSN) analysis of the entire CsoR superfamily, which together with the first crystallographic structure of a CstR and comprehensive mass spectrometry-based kinetic profiling experiments, reveal new insights into the molecular basis of RSS specificity in CstRs. We find that the more N-terminal cysteine is the attacking Cys in CstR and is far more nucleophilic than in a CsoR. Moreover, our CstR crystal structure is markedly asymmetric and chemical reactivity experiments reveal the functional impact of this asymmetry. Substitution of the Asn wedge between the resolving and the attacking thiol with Ala significantly decreases asymmetry in the crystal structure and markedly impacts the distribution of species, despite adopting the same global structure as the parent repressor. Companion NMR, SAXS and molecular dynamics simulations reveal that the structural and functional asymmetry can be traced to fast internal dynamics of the tetramer. Furthermore, this asymmetry is preserved in all CstRs and with all oxidants tested, giving rise to markedly distinct distributions of crosslinked products. Our exploration of the sequence, structural, and kinetic features that determine oxidant-specificity suggest that the product distribution upon RSS exposure is determined by internal flexibility.

Taking a closer look into Crohn's disease and cerebral palsy.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD), is a chronic, immune-mediated disease involving the gastrointestinal tract. Cerebral palsy (CP) has not been associated with IBD aside from a single previously published case series. In this study, we describe two cases of CD in patients with CP. Both patients had global developmental delay. They were also underweight and exclusively gastrostomy tube dependent for nutrition. By detailing their clinical courses, we illustrate the importance of becoming familiar with the extraintestinal manifestations of IBD. In the setting of developmental delay and its associated communication barriers, the evaluation of IBD might shift from assessing subjective symptoms to recognizing the subtle presentations of the disease, including anemia, weight loss, malnutrition, and failure to thrive. We also hypothesize that malnutrition and a change in the gastrointestinal microbiota associated exclusively with enteral nutrition may be linked to the development of CD in patients with CP. Overall, this study provides information for clinicians caring for patients with CP or developmental delay, and how to recognize extraintestinal manifestations of IBD.

Characterizing the role of dermatologists in developing artificial intelligence for assessment of skin cancer.

BACKGROUND: The use of artificial intelligence (AI) for skin cancer assessment has been an emerging topic in dermatology. Leadership of dermatologists is necessary in defining how these technologies fit into clinical practice. OBJECTIVE: To characterize the evolution of AI in skin cancer assessment and characterize the involvement of dermatologists in developing these technologies. METHODS: An electronic literature search was performed using PubMed by searching machine learning or artificial intelligence combined with skin cancer or melanoma. Articles were included if they used AI for screening and diagnosis of skin cancer using data sets consisting of dermoscopic images or photographs of gross lesions. RESULTS: Fifty-one articles were included, and 41% of these had dermatologists included as authors. Articles that included dermatologists described algorithms built with more images versus articles that did not include dermatologists (mean, 12,111 vs 660 images, respectively). In terms of underlying technology, AI used for skin cancer assessment has followed trends in the field of image recognition. LIMITATIONS: This review focused on models described in the medical literature and did not account for those described elsewhere. CONCLUSIONS: Greater involvement of dermatologists is needed in thinking through issues in data collection, data set biases, and applications of technology. Dermatologists can provide access to large, diverse data sets that are increasingly important for building these models.

Revisiting the pathobiology of scurvy: a review of the literature in the context of a challenging case.

Scurvy is a nutritional disorder resulting from vitamin C deficiency. Although rare in developing countries, scurvy continues to develop in settings of limited dietary intake such as post-gastrointestinal surgery and restrictive dietary habits. The disease primarily affects the skin and soft tissue. As the state of deficiency persists, hematological and immunological sequelae may develop. The classic signs of scurvy are not always present and can be altered by the presence of other comorbidities. In this article, we present a challenging case of scurvy in an older male from an urban tertiary healthcare setting. We review the atypical and uncommon clinical and pathological findings of scurvy including those seen in the skin, blood, and bone marrow. We also review contemporary research findings that provide a better understanding of the pathogenicity and clinical manifestations of vitamin C deficiency.

Monitoring the topical delivery of ultrasmall gold nanoparticles using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a promising imaging modality for skin cancer diagnosis. However, this capability has been hindered by the low contrast between normal and neoplastic tissue. To overcome this limitation, gold nanoparticles have been used to enhance the contrast in OCT images and are topically administered to reduce the risk of systematic side effects associated with intravenous injection. To ensure efficient penetration and distribution of the nanoparticles, an enhanced delivery strategy is required. In this porcine study, we assessed two delivery methods: (a) using dimethyl sulfoxide (DMSO) and (b) via sonophoresis. MATERIALS AND METHODS: The gold nanoparticles were topically applied on pig skin before evaluating DMSO and sonophoresis as penetration enhancers in topical administration. The OCT images were taken from the same locations to monitor signal change. CONCLUSION: The combination of DMSO and sonophoresis is an effective method to enhance the penetration and diffusion rate of nanoparticles during topical administration. SIGNIFICANCE: Topical administration of nanoparticles is advantageous in dermatological applications. Nevertheless, efficient topical delivery remains a challenge. DMSO and sonophoresis can be used as two effective approaches to enhance topical delivery of nanoparticles.

Photoacoustic/Ultrasound/Optical Coherence Tomography Evaluation of Melanoma Lesion and Healthy Skin in a Swine Model.

The marked increase in the incidence of melanoma coupled with the rapid drop in the survival rate after metastasis has promoted the investigation into improved diagnostic methods for melanoma. High-frequency ultrasound (US), optical coherence tomography (OCT), and photoacoustic imaging (PAI) are three potential modalities that can assist a dermatologist by providing extra information beyond dermoscopic features. In this study, we imaged a swine model with spontaneous melanoma using these modalities and compared the images with images of nearby healthy skin. Histology images were used for validation.