The effect of combined red, blue, and near-infrared light-emitting diode (LED) photobiomodulation therapy on speed of wound healing after superficial ablative fractional resurfacing.

Objective of the study is to assess the effects of wound healing with a commercially available light emitting diode (LED) photo biomodulation (PBM) device that emits three wavelengths (465, 640 and 880nm) after ablative fractional laser (AFL) treatment to healthy skin on the bilateral inner biceps. We conducted a prospective intraindividual randomized controlled study with 25 volunteers. AFL treatment was performed on healthy skin of the bilateral inner biceps. Subjects applied the LED light device for 30 min to the assigned bicep 3 times a week over 4 weeks, beginning on day 0. Subjects were followed up on days 2, 4, 6, 9, 13, 20 and 27 for treatment with the PBM device, clinical digital photography of the test and control sites, and in-person subject assessment, with follow ups on days 34 and 55 for clinical photography and assessment. Three blinded evaluators were asked to determine which bicep healed faster between day 0 to day 13. Pain, discomfort, and itch were also assessed. The three blinded evaluators chose the treatment arm as the faster healed arm in greater than 50% of the images, although the results were not statistically significant. There was no statistically significant difference between test and control arms in terms of pain, discomfort and itch. In conclusion, PBM therapy has the potential to improve wound healing. In this study, a three wavelength PBM device resulted in some subjects achieving faster healing after AFL but the results were not statistically significant.

Feasibility of photoacoustic-guided ultrasound treatment for port wine stains.

BACKGROUND AND OBJECTIVES: Port wine birthmark, also known as port wine stain (PWS) is a skin discoloration characterized by red/purple patches caused by vascular malformation. PWS is typically treated by using lasers to destroy abnormal blood vessels. The laser heating facilitates selective photothermolysis of the vessels and attenuates quickly in the tissue due to high optical scattering. Therefore, residual abnormal capillaries deep in the tissue survive and often lead to the resurgence of PWS. Ultrasound (US) has also been proposed to treat PWS, however, it is nonselective with respect to the vasculature but penetrates deeper into the tissue. We aim to study the feasibility of a hybrid PWS treatment modality combining the advantages of both modalities. MATERIALS AND METHODS: In this manuscript, we propose a photoacoustic (PA) guided US focusing methodology for PWS treatment which combines the optical contrast-based selectivity with US penetration to focus the US energy onto the vasculature. The PA signals collected by the transducers, when time-reversed, amplified, and transmitted, converge onto the PWS, thus minimally affecting the neighboring tissue. We performed two- and three-dimensional simulations that mimic realistic transducers and medium properties in this proof of concept study. RESULTS: The time-reversed PA signals when transmitted from the transducers converged onto the vasculature, as expected, thus reducing the heating of the neighboring tissue. We observed that while the US focus is indeed affected due to experimental factors such as limited-view, large detector separation and finite detection bandwidth, and so forth, the US did focus completely or partially onto the vasculature demonstrating the feasibility of the proposed methodology. CONCLUSION: The results demonstrate the potential of the proposed methodology for PWS treatment. This treatment method can destroy the deeper capillaries while minimally heating the neighboring tissue, thus reducing the chances of the resurgence of PWS and as well as cosmetic scarring.

A core outcome domain set for clinical research on capillary malformations (the COSCAM project): an e-Delphi process and consensus meeting.

BACKGROUND: There is limited evidence on the best available treatment options for capillary malformations (CMs), mainly due to the absence of uniform outcome measures in trials on therapies. A core outcome set (COS) enables standard reporting of trial outcomes, which facilitates comparison of treatment results. OBJECTIVES: To develop a core outcome domain set (CDS), as part of a core outcome set (COS), for clinical research on CMs. METHODS: Sixty-seven potentially relevant outcome subdomains were recognized based on the literature, focus group sessions, and input from the COSCAM working group. These outcome subdomains were presented in an online Delphi study to CM experts (medical specialists and authors of relevant literature) and (parents of) patients with CM (international patient associations). During three e-Delphi study rounds, the participants repeatedly scored the importance of these outcome subdomains on a seven-point Likert scale. Participants could also propose other relevant outcome subdomains. Consensus was defined as ≥ 80% agreement as to the importance of an outcome subdomain among both stakeholder groups. The CDS was finalized during an online consensus meeting. RESULTS: In total 269 participants from 45 countries participated in the first e-Delphi study round. Of these, 106 were CM experts from 32 countries, made up predominantly of dermatologists (59%) and plastic surgeons (18%). Moreover, 163 (parents of) patients with CM from 28 countries participated, of whom 58% had Sturge-Weber syndrome. During the two subsequent e-Delphi study rounds, 189 and 148 participants participated, respectively. After the entire consensus process, consensus was reached on 11 outcome subdomains: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. CONCLUSIONS: We recommend the CDS to be used as a minimum reporting standard in all future trials of CM therapy. Our next step will be to select suitable outcome measurement instruments to score the core outcome subdomains. What is already known about this topic? Besides physical and functional sequelae, capillary malformations (CMs) often cause emotional and social burden. The lack of uniform outcome measures obstructs proper evaluation and comparison of treatment strategies. As a result, there is limited evidence on the best available treatment options. The development of a core outcome set (COS) may improve standardized reporting of trial outcomes. What does this study add? A core outcome domain set (CDS), as part of a COS, was developed for clinical research on CMs. International consensus was reached on the recommended core outcome subdomains to be measured in CM trials: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. This CDS enables the next step in the development of a COS, namely to reach consensus on the core outcome measurement instruments to score the core outcome subdomains. What are the clinical implications of this work? The obtained CDS will facilitate standardized reporting of treatment outcomes, thereby enabling proper comparison of treatment results. This comparison is likely to provide more reliable information for patients about the best available treatment options.

Analysis of port-wine birthmark vascular characteristics by location: Utility of optical coherence tomography mapping.

INTRODUCTION: Port-wine birthmarks (PWBs) are congenital capillary malformations that can be located on any area of the body. Vascular features include vessel size, depth, and density, which can greatly differ between patients, individual lesions, and even sites within the same lesion. Previous studies have determined that the location of PWB lesions has impacted their clinical response to laser treatment. OBJECTIVE: We utilized dynamic optical coherence tomography (D-OCT) to measure in vivo vessel diameter, density, and superficial plexus depth in patients of all ages with PWB on various sites of the body. We hypothesized that these vascular characteristics would differ according to body location. MATERIALS AND METHODS: Patients who had a PWB and presented to clinic at three sites for treatment with the pulsed dye laser (PDL) were enrolled into the study. A D-OCT scanner was utilized for noninvasive, in vivo imaging of PWB lesions. The depth of the top portion of the superficial vascular plexus was estimated as the depth at which the vessel density reaches 50% of the maximum. Vessel diameter and density were calculated by incorporated software algorithm. RESULTS: A total of 108 patients were enrolled into the study. There was a total of 204 measurements of PWB lesions. Of all patients, 56.5% (n = 61) reported having a previous treatment with PDL. Of all D-OCT scans, 62.3% (n = 127) were located on the head, 14.2% (n = 29) the upper extremities, 8.3% (n = 17) the lower extremities, 7.8% (n = 16) the trunk, and 7.8% (n = 15) the neck. All locations were compared for each vascular characteristic. For superficial plexus depth, lesions on the head were significantly shallower than those on the upper extremities (217 vs. 284 µm; p < 0.001) and lower extremities (217 vs. 309 µm; p < 0.001). For vessel diameter, lesions on the head had significantly larger vessels than those on the upper extremities (100 vs. 72 µm; p = 0.001). For vessel density, lesions on the head had significantly denser vessels than those on the trunk (19% vs. 9.6%; p = 0.039) and upper extremities (19% vs. 9.3%; p < 0.001) CONCLUSIONS: PWB lesions have distinct vascular characteristics, which can be associated with their body location. This includes superficial vascular plexus depth as well as vessel diameter and density.

Laser Treatment of Hypopigmentation in Scars: A Review.

BACKGROUND: Despite history of multiple treatment modalities, repigmentation of hypopigmented scars remains a difficult clinical problem. OBJECTIVE: The purpose of this review is to evaluate the literature on laser and combination laser plus adjunct topical therapy for hypopigmented burn and traumatic scars. MATERIALS AND METHODS: A search on PubMed and on Oxford Academic was conducted with additional relevant literature obtained from reference lists. RESULTS: Treatment regimens that address hypopigmentation within scars were reviewed. A combination of nonablative fractional or ablative fractional laser treatment with topical prostaglandin analogue with or without topical retinoid were found to result in superior repigmentation. CONCLUSION: Reliable improvement of hypopigmentation in scars after laser treatment is challenging. Laser can achieve success in some cases. Ultraviolet laser can achieve modest repigmentation; however, results are short-lived and require continued re-treatment. Modest improvement in pigmentation is seen with nonablative fractional laser or ablative fractional laser alone and enhanced repigmentation is demonstrated when combining fractional laser resurfacing with topical application of synthetic prostaglandin analogues and other known modulators of melanogenesis.

Port-wine Birthmarks: Update on Diagnosis, Risk Assessment for Sturge-Weber Syndrome, and Management.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder that classically presents with a triad of vascular anomalies affecting the skin, eyes, and brain. Previously, the trigeminal nerve distribution of a port-wine birthmark (PWB) of the face was used to identify risk of SWS. However, recent evidence has demonstrated that PWBs are vascular, not neurologic, in embryologic origin, and facial PWBs at highest risk for the brain involvement of SWS involve the forehead location. Furthermore, a PWB involving the upper or lower eyelid carries a risk of glaucoma, which requires lifelong monitoring. The gold standard of treatment for PWB is the pulsed dye laser, which has many advantages when started as early as possible in infancy. In this review, we discuss the locations of facial PWBs at risk for neurologic and ophthalmologic complications, the differential diagnosis of facial vascular birthmarks, recommendations for patient referral(s) when needed, and the advantages of early laser therapy when desired for the PWB. We also provide additional resources for pediatricians to support patients and their families.

Depression and interleukin-6 signaling: A Mendelian Randomization study.

BACKGROUND: A large body of research has reported associations between depression and elevated interleukin-6 (IL-6), a cytokine with several roles including pro-inflammatory signaling. The nature and directionality of this relationship are not yet clear. In this study we use Mendelian Randomization to examine the possibility of a causal relationship between IL-6 and depressive symptoms, and to explore multiple signaling pathways that could serve as mechanisms for this relationship. METHODS: This study uses a two-sample Mendelian Randomization design. Data come from the UK Biobank (n = 89,119) and published summary statistics from six existing GWAS analyses. The primary analysis focuses on the soluble interleukin-6 receptor (sIL-6R), which is involved in multiple signaling pathways. Exploratory analyses use C-reactive protein (CRP) and soluble glycoprotein 130 (sgp130) to further examine potential underlying mechanisms. RESULTS: Results are consistent with a causal effect of sIL-6R on depression (PCA-IVW Odds Ratio: 1.023 (95% Confidence Interval: 1.006-1.039), p = 0.006). Exploratory analyses demonstrate that the relationship could be consistent with either decreased classical signaling or increased trans signaling as the underlying mechanism. DISCUSSION: These results strengthen the body evidence implicating IL-6 signaling in depression. When compared with existing observational and animal findings, the direction of these results suggests involvement of IL-6 trans signaling. Further study is needed to examine whether IL6R genetic variants might influence IL-6 trans signaling in the brain, as well as to explore other potential pathways linking depression and inflammation.

Vascular characteristics of port wine birthmarks as measured by dynamic optical coherence tomography.

BACKGROUND: Port wine birthmarks (PWBs) are congenital capillary malformations. Vessel characteristics, such as diameter and depth, may impact presentation and outcomes. They can be imaged using dynamic optical coherence tomography, a high-resolution, noninvasive imaging method. PURPOSE: We conducted a cross-sectional observational study to measure in vivo vascular characteristics as a function of PWB color. METHODS: Patients undergoing treatment for PWB were recruited from 3 sites. PWBs were classified by color. Dynamic optical coherence tomography images with calculations were obtained. RESULTS: One hundred eight patients were enrolled. Mean age correlated with PWB color, with birthmarks being lighter in younger patients and darker in older patients (P < .01). Mean superficial plexus depth was significantly shallower in purple PWBs than in pink PWBs. Color was not associated with significant differences in mean superficial vessel density or diameter. Among pink PWBs, each 10-year increase in age was associated with a 10.6-µm increase in superficial plexus depth. Among purple PWBs, each 10-year increase in age was associated with a 16.2-µm reduction in superficial plexus depth. In lesions without prior treatment, vessel density was 12.7% lower in purple PWBs than in pink PWBs. CONCLUSION: Superficial vessels of purple PWBs were significantly closer to the epidermis than those of pink PWBs, which might impact optimal laser parameters.

Assessing the Outcomes of Focused Heating of the Skin by a Long-Pulsed 1064 nm Laser with an Integrated Scanner, Infrared Thermal Guidance, and Optical Coherence Tomography.

BACKGROUND AND OBJECTIVE: Long-term benefits can be predicted by the incorporation of more intelligent systems in lasers and other devices. Such systems can produce more reliable zones of thermal injury when used in association with non-invasive monitoring and precise laser energy delivery. The more classical endpoint of tumor destruction with radiofrequency or long-pulsed (LP) 1064 nm laser is the non-specific appearance of tissue graying and tissue contraction. Herein we discuss combining non-invasive LP 1064 nm Nd:YAG treatment with the assistance of optical coherence tomography (OCT) and the forward-looking infrared (FLIR) thermal camera while testing literature-based formulae for thermal destruction. STUDY DESIGN/MATERIALS AND METHODS: The skin on the forearm and back of two consenting volunteers was marked and anesthetized with lidocaine with epinephrine. The parameters of a scanner-equipped LP 1064 nm Nd:YAG laser were adjusted to achieve an epidermal/superficial dermal heating of between 50°C and 60°C over a specified time course. Experimental single treatments examined various adjusted parameters including, fluence, pulse overlap, pulse duration, scan size, and pulse rate. A FLIR camera was used to record skin temperature. Outcome measures included skin temperature, post-treatment appearance, and OCT assessment of skin and vascular damage. The clinical response of each treatment was followed daily for 4 weeks. RESULTS: Optimal protocols initially raised the skin temperature to between 55°C and 60°C, which was carefully maintained using subsequent laser passes over a 60-second time course. Immediately post laser, clinical responses included erythema, edema, and blistering. Immediate OCT revealed increased vascularity with intact, dilated blood vessels. Prolonged exposure above 60°C resulted in sub-epidermal blistering and an absence of blood flow in the treatment area with prolonged healing. CONCLUSION: The LP 1064 nm laser can be used to achieve heat-related tissue injury, though the narrow parameters necessary for the desired endpoint require the assistance of IR thermal regulation to avoid unacceptable outcomes. The use of the laser scanner ensures precise energy delivery over a defined treatment area. Future studies might explore this as a selective hyperthermic method for the treatment of non-melanoma skin cancer. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Lasers, Birthmarks, and Sturge-Weber Syndrome: A Pilot Survey.

BACKGROUND AND OBJECTIVES: There is limited or no data on the experience of patients with Sturge-Weber Syndrome (SWS) and/or their parents who seek out laser treatments for their port-wine birthmark (PWB). Our study aimed to develop a survey to understand patient perspectives on laser therapy and subsequent behaviors while focusing on three elements of the health belief model: perceived susceptibility, perceived benefits, and perceived barriers. STUDY DESIGN/MATERIALS AND METHODS: A 31 item survey was developed and sent to 650 members of the Sturge-Weber Foundation. The survey included questions regarding four domains: demographics, disease severity, laser experience, and perceptions and behaviors. Logistic regression models and bivariate analyses were conducted to analyze the results. RESULTS: Among the 123 respondents, earlier initiation of laser treatments was associated with greater birthmark satisfaction. Overall satisfaction increased up to 20 treatments and then leveled off. Color satisfaction increased up to 100 laser treatments; however, the flatness of the PWB was not associated with the number of laser treatments. The perceived benefits of lasers were not associated with the number of lifetime treatments or with spending. However, the perceived susceptibility was associated with greater spending on travel and medical expenses. CONCLUSION: The results of our survey provide insight into SWS patient experiences, beliefs, and behaviors regarding laser therapy. Further exploration of these variables may allow for the improvement of the care experience. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

A Clinical Perspective on the Automated Analysis of Reflectance Confocal Microscopy in Dermatology.

BACKGROUND AND OBJECTIVES: Non-invasive optical imaging has the potential to provide a diagnosis without the need for biopsy. One such technology is reflectance confocal microscopy (RCM), which uses low power, near-infrared laser light to enable real-time in vivo visualization of superficial human skin from the epidermis down to the papillary dermis. Although RCM has great potential as a diagnostic tool, there is a need for the development of reliable image analysis programs, as acquired grayscale images can be difficult and time-consuming to visually assess. The purpose of this review is to provide a clinical perspective on the current state of artificial intelligence (AI) for the analysis and diagnostic utility of RCM imaging. STUDY DESIGN/MATERIALS AND METHODS: A systematic PubMed search was conducted with additional relevant literature obtained from reference lists. RESULTS: Algorithms used for skin stratification, classification of pigmented lesions, and the quantification of photoaging were reviewed. Image segmentation, statistical methods, and machine learning techniques are among the most common methods used to analyze RCM image stacks. The poor visual contrast within RCM images and difficulty navigating image stacks were mediated by machine learning algorithms, which allowed the identification of specific skin layers. CONCLUSIONS: AI analysis of RCM images has the potential to increase the clinical utility of this emerging technology. A number of different techniques have been utilized but further refinements are necessary to allow consistent accurate assessments for diagnosis. The automated detection of skin cancers requires more development, but future applications are truly boundless, and it is compelling to envision the role that AI will have in the practice of dermatology. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Light-based treatment of pediatric port-wine birthmarks.

Port-wine birthmarks (PWBs) are progressive vascular malformations with significant disfigurement and psychosocial morbidity; early light-based treatment has shown improved outcomes in the pediatric population. Somatic mosaic mutations underly the progressive nature of PWBs and explain the significant differences in response and heterogeneity of vessel architecture in the pediatric population when compared to the adult cohort. Here, we summarize a review of pediatric specific literature on the various light-based treatment modalities, including pulsed dye laser, near-infrared lasers, and intense pulsed light, providing the various indications, tips, advantages, and disadvantages for the pediatric dermatologist.

Genome-Wide Association Meta-Analysis of Individuals of European Ancestry Identifies Suggestive Loci for Sodium Intake, Potassium Intake, and Their Ratio Measured from 24-Hour or Half-Day Urine Samples.

BACKGROUND: Excess sodium intake and insufficient potassium intake are risk factors for hypertension, but there is limited knowledge regarding genetic factors that influence intake. Twenty-hour or half-day urine samples provide robust estimates of sodium and potassium intake, outperforming other measures such as spot urine samples and dietary self-reporting. OBJECTIVE: The aim of this study was to investigate genomic regions associated with sodium intake, potassium intake, and sodium-to-potassium ratio measured from 24-h or half-day urine samples. METHODS: Using samples of European ancestry (mean age: 54.2 y; 52.3% women), we conducted a meta-analysis of genome-wide association studies in 4 cohorts with 24-h or half-day urine samples (n = 6,519), followed by gene-based analysis. Suggestive loci (P < 10-6) were examined in additional European (n = 844), African (n = 1,246), and Asian (n = 2,475) ancestry samples. RESULTS: We found suggestive loci (P < 10-6) for all 3 traits, including 7 for 24-h sodium excretion, 4 for 24-h potassium excretion, and 4 for sodium-to-potassium ratio. The most significant locus was rs77958157 near cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT) , a gene involved in eating behavior and appetite regulation (P = 2.3 × 10-8 with sodium-to-potassium ratio). Two suggestive loci were replicated in additional samples: for sodium excretion, rs12094702 near zinc finger SWIM-type containing 5 (ZSWIM5) was replicated in the Asian ancestry sample reaching Bonferroni-corrected significance (P = 0.007), and for potassium excretion rs34473523 near sodium leak channel (NALCN) was associated at a nominal P value with potassium excretion both in European (P = 0.043) and African (P = 0.043) ancestry cohorts. Gene-based tests identified 1 significant gene for sodium excretion, CDC42 small effector 1 (CDC42SE1), which is associated with blood pressure regulation. CONCLUSIONS: We identified multiple suggestive loci for sodium and potassium intake near genes associated with eating behavior, nervous system development and function, and blood pressure regulation in individuals of European ancestry. Further research is needed to replicate these findings and to provide insight into the underlying genetic mechanisms by which these genomic regions influence sodium and potassium intake.

A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking.

Many vaccines require adjuvants to enhance immunogenicity, but there are few safe and effective intradermal (i.d.) adjuvants. Murine studies have validated the potency of laser illumination of skin as an adjuvant for i.d. vaccination with advantages over traditional adjuvants. We report a pilot clinical trial of low-power, continuous-wave, near-infrared laser adjuvant treatment, representing the first human trial of the safety, tolerability, and cutaneous immune cell trafficking changes produced by the laser adjuvant. In this trial we demonstrated a maximum tolerable energy dose of 300 J/cm2 to a spot on the lower back. The irradiated spot was biopsied 4 h later, as was a control spot. Paired biopsies were submitted for histomorphologic and immunohistochemical evaluation in a blinded fashion as well as quantitative PCR analysis for chemokines and cytokines. Similar to prior murine studies, highly significant reductions in CD1a+ Langerhans cells in the dermis and CD11c+ dermal dendritic cells were observed, corresponding to the increased migratory activity of these cells; changes in the epidermis were not significant. There was no evidence of skin damage. The laser adjuvant is a safe, well-tolerated adjuvant for i.d. vaccination in humans and results in significant cutaneous immune cell trafficking.-Gelfand, J. A., Nazarian, R. M., Kashiwagi, S., Brauns, T., Martin, B., Kimizuka, Y., Korek, S., Botvinick, E., Elkins, K., Thomas, L., Locascio, J., Parry, B., Kelly, K. M., Poznansky, M. C. A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking.

Pupillometry measures of autonomic nervous system regulation with advancing age in a healthy pediatric cohort.

PURPOSE: To determine if variables of the pupillary light response mature with age and sex in a healthy pediatric cohort and the utility of pupillometry in assessment among pediatric participants. METHODS: After 1 min in a dark room to establish baseline, pupillometry was performed on 323 healthy, pediatric participants (646 eyes; 2-21 years; 175 females). Variables included initial pupil diameter, pupil diameter after light stimulus, percent pupillary constriction, latency to onset of constriction, average constriction velocity, maximum constriction velocity, average dilation velocity, and time from light stimulus to 75% of the initial pupil diameter. Data analyses employed ANOVAs and non-linear regressions. RESULTS: Analyses of age group differences revealed that participants 12-21 years old had a larger initial pupil diameter and pupil diameter after light stimulus, with males aged 12-18 years demonstrating a larger pupil diameter than all younger participants (ps < 0.05). Participants 12-18 years old had a slower maximum constriction velocity than participants 6-11 years old, with no sex differences (ps < 0.05). Furthermore, males aged 12-18 years old had a smaller percent constriction than males 6-11 years old (ps < 0.05). Regressions revealed that percent constriction and dilation velocity seemed to mature linearly, initial pupil diameter and ending pupil diameter matured quadratically, and the constriction velocity terms matured cubically. CONCLUSIONS: Results revealed maturation of the pupillary light response by age and sex in healthy pediatric participants. Given the value of the pupillary light response as a biomarker, the results provide normative benchmarks for comparison in health and disease, including opiate-exposed and concussion patients.

Microvascular Effects of Pulsed Dye Laser in Combination With Oxymetazoline.

BACKGROUND AND OBJECTIVE: Oxymetazoline, an α-1A agonist, is approved by the United States Food and Drug Administration (FDA) for treatment of persistent facial erythema associated with rosacea and induces vasoconstriction by interacting with α receptors. The objective of our study was to study the microvascular effects of oxymetazoline and pulsed dye laser (PDL). MATERIALS AND METHODS: A dorsal window chamber was surgically installed on 20 mice. Each animal was assigned to one of four experimental groups: saline alone, oxymetazoline alone (10 µl applied once daily × 7 days), saline + PDL (saline applied 5 minutes before PDL irradiation [10 mm spot, 1.5 ms pulse duration, 7 J/cm2 delivered to epidermis]), or oxymetazoline + PDL (10 µl oxymetazoline applied 5 minutes before PDL and then once daily × 7 days). Brightfield and laser speckle imaging were performed for 7 days to monitor vascular architectural and functional changes. RESULTS: We observed persistent blood flow in all of the saline-only and oxymetazoline-only experiments. A higher rate of vascular shutdown was observed with oxymetazoline + PDL (66.7%) compared with saline + PDL alone (16.7%). Oxymetazoline application increased venule diameter at 5 minutes post-application and decreased both arteriole and venule diameters at 60 minutes post-application. CONCLUSION: The combination protocol of oxymetazoline + PDL induces persistent vascular shutdown observed 7 days after irradiation. This result may be associated with the acute vascular effects of oxymetazoline. Oxymetazoline + PDL should be evaluated as a treatment for cutaneous vascular disease, including rosacea and port wine birthmarks. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Ablative Fractional Resurfacing for Chronic Wounds from Traumatic Scarring: A Case Report and Literature Review.

Ablative fractional resurfacing (AFR) can be utilized to improve scar appearance, texture, pain and associated contractures. Non-healing ulcers can also develop in areas of scarring and, in some cases, AFR can be utilized to heal these chronic wounds. We present a case of scarring with non-healing ulceration refractory to wound care, debridement and hydrotherapy successfully healed in four sessions with AFR using a 2940 nm Er:YAG laser. We review the literature on AFR for wound healing including potential mechanisms. AFR can be considered for non-healing ulcers in areas of scarring, once malignancy and infection are ruled out, and has the potential to provide relief for these suffering patients.J Drugs Dermatol. 2020;19(11): doi:10.36849/JDD.2020.5444.

Engineering two species of yeast as cell factories for 2'-fucosyllactose.

Oligosaccharides present in human breast milk have been linked to beneficial effects on infant health. Inclusion of these human milk oligosaccharides (HMOs) in infant formula can recapitulate these health benefits. As a result, there is substantial commercial interest in a cost-effective source of HMOs as infant formula ingredients. Here we demonstrate that the yeast species Saccharomyces cerevisiae and Yarrowia lipolytica both can be engineered to produce 2'-fucosyllactose (2'FL), which is the most abundant oligosaccharide in human breast milk, at high titer and productivity. Both yeast species were modified to enable uptake of lactose and synthesis of GDP-fucose - the two precursors of 2'FL - by installing a lactose transporter and enzymes that convert GDP-mannose to GDP-fucose. Production of 2'FL was then enabled by expression of α-1,2-fucosyltransferases from various organisms. By screening candidate transporters from a variety of sources, we identified transporters capable of exporting 2'FL from yeast, which is a key consideration for any biocatalyst for 2'FL production. In particular, we identified CDT2 from Neurospora crassa as a promising target for further engineering to improve 2'FL efflux. Finally, we demonstrated production of 2'FL in fermenters at rates and titers that indicate the potential of engineered S. cerevisiae and Y. lipolytica strains for commercial 2'FL production.

Hyperspectral imaging in automated digital dermoscopy screening for melanoma.

OBJECTIVES: Early melanoma detection decreases morbidity and mortality. Early detection classically involves dermoscopy to identify suspicious lesions for which biopsy is indicated. Biopsy and histological examination then diagnose benign nevi, atypical nevi, or cancerous growths. With current methods, a considerable number of unnecessary biopsies are performed as only 11% of all biopsied, suspicious lesions are actually melanomas. Thus, there is a need for more advanced noninvasive diagnostics to guide the decision of whether or not to biopsy. Artificial intelligence can generate screening algorithms that transform a set of imaging biomarkers into a risk score that can be used to classify a lesion as a melanoma or a nevus by comparing the score to a classification threshold. Melanoma imaging biomarkers have been shown to be spectrally dependent in Red, Green, Blue (RGB) color channels, and hyperspectral imaging may further enhance diagnostic power. The purpose of this study was to use the same melanoma imaging biomarkers previously described, but over a wider range of wavelengths to determine if, in combination with machine learning algorithms, this could result in enhanced melanoma detection. METHODS: We used the melanoma advanced imaging dermatoscope (mAID) to image pigmented lesions assessed by dermatologists as requiring a biopsy. The mAID is a 21-wavelength imaging device in the 350-950 nm range. We then generated imaging biomarkers from these hyperspectral dermoscopy images, and, with the help of artificial intelligence algorithms, generated a melanoma Q-score for each lesion (0 = nevus, 1 = melanoma). The Q-score was then compared to the histopathologic diagnosis. RESULTS: The overall sensitivity and specificity of hyperspectral dermoscopy in detecting melanoma when evaluated in a set of lesions selected by dermatologists as requiring biopsy was 100% and 36%, respectively. CONCLUSION: With widespread application, and if validated in larger clinical trials, this non-invasive methodology could decrease unnecessary biopsies and potentially increase life-saving early detection events. Lasers Surg. Med. 51:214-222, 2019. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Conformational Ensembles of Calmodulin Revealed by Nonperturbing Site-Specific Vibrational Probe Groups.

Seven native residues on the regulatory protein calmodulin, including three key methionine residues, were replaced (one by one) by the vibrational probe amino acid cyanylated cysteine, which has a unique CN stretching vibration that reports on its local environment. Almost no perturbation was caused by this probe at any of the seven sites, as reported by CD spectra of calcium-bound and apo calmodulin and binding thermodynamics for the formation of a complex between calmodulin and a canonical target peptide from skeletal muscle myosin light chain kinase measured by isothermal titration. The surprising lack of perturbation suggests that this probe group could be applied directly in many protein-protein binding interfaces. The infrared absorption bands for the probe groups reported many dramatic changes in the probes' local environments as CaM went from apo- to calcium-saturated to target peptide-bound conditions, including large frequency shifts and a variety of line shapes from narrow (interpreted as a rigid and invariant local environment) to symmetric to broad and asymmetric (likely from multiple coexisting and dynamically exchanging structures). The fast intrinsic time scale of infrared spectroscopy means that the line shapes report directly on site-specific details of calmodulin's variable structural distribution. Though quantitative interpretation of the probe line shapes depends on a direct connection between simulated ensembles and experimental data that does not yet exist, formation of such a connection to data such as that reported here would provide a new way to evaluate conformational ensembles from data that directly contains the structural distribution. The calmodulin probe sites developed here will also be useful in evaluating the binding mode of calmodulin with many uncharacterized regulatory targets.