Dermatologic aspects of bed bug epidemic: an atlas of differential diagnosis.

Bed bug infestation rate has gone through an unforeseen increase in the past decades worldwide. Their resurgence is a consequence of numerous factors, including growing population density, increased international travel and the spread of insecticide resistance. Bed bug infestation is often revealed by skin symptoms appearing after their bite in sensitive patients. Medical professionals encountering patients with bed bug bites have responsibility for recognizing the condition and for instructing patients about the necessary measures for eradication. Setting the correct diagnosis, however, is not unequivocal as several skin diseases with autoimmune, immune-mediated aetiology or other arthropod stings and bites may present with similar symptoms. In this review we provide a differential diagnostic guide and an atlas of clinical pictures assigned to the diagnoses. We highlight those dermatological findings where the possibility of bed bug bite arises and identify key elements that help in the differentiation so as to avoid unnecessary diagnostic tests and force early start of extermination.

A Family with Palmar and Plantar Hyperkeratosis: A Quiz.

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Efficiency of long-term high-dose intravenous ascorbic acid therapy in locally advanced basal cell carcinoma - a pilot study.

INTRODUCTION: The anti-cancer properties of high-dose intravenous ascorbic acid have been demonstrated in various malignancies. In our recent study, we tested topically applied ascorbic acid to treat basal cell carcinoma (BCC), and achieved a good clinical response. AIM: Based on these results, we decided to examine the efficacy and tolerability of high-dose intravenous ascorbic acid (IVA) for locally advanced BCC. MATERIAL AND METHODS: In this pilot study, patients diagnosed with locally advanced BCC who were not amenable to radiation, surgical or local therapy (no other treatment option was available at the time) received intravenous ascorbic acid (1-1.8 g/kg), in an outpatient setting, 1-3 times per week for a mean duration of 42 ±23.6 weeks. This therapy was generally well tolerated. RESULTS: Among 4 patients who had a total of 165 (mean: 41 ±51, range: 1-114) skin lesions, 3 patients achieved stable disease and one had progressive disease. There was substantial variability in individual tumor response to therapy. With the aid of two-photon microscopy and second harmonic generation imaging techniques, alterations in collagen structure were observed between tumor nests during IVA therapy. CONCLUSIONS: Our results suggest that IVA is well tolerated in a small group of patients with extensive BCCs. However, in the era of smoothened (Smo) receptor inhibitors, it may only be considered as an adjuvant therapy in treatment-resistant cases.

Intralesional therapy for the treatment of keratoacanthoma.

Keratoacanthoma (KA) is a common epidermal tumor that originates from the hair follicle of the skin. It is generally considered as a benign neoplasm, but in rare cases, it can also transform into squamous cell carcinoma. Although surgical excision with a safety margin is considered to be the gold standard treatment for most subtypes of KA, several other treatment options are also available. Intralesional therapy is one of these options, which could be cosmetically and functionally a better alternative to surgical removal, while it provides similar outcomes. It is more effective than topical treatments, yet fewer side effects may be seen than in systemic treatments. Based on the literature, the most commonly used intralesional agent is methotrexate, followed by 5-fluorouracil and interferon alpha. Regardless of the advantages, which make intralesional therapy a desirable treatment alternative, guidelines for the intralesional treatment of KA are not yet established. A histopathological confirmation before the start of treatment is still recommended to prevent any possible misdiagnosis of KA for SCC. In our present study, we set out to review the current state of the art of the intralesional treatment of KA.

Evaluation of ovarian reserve in women with psoriasis.

The aim of this study is to evaluate ovarian reserve in women with psoriasis. Thirty-six women with psoriasis and 36 healthy women were enrolled in this prospective study. On day 3 of the menstrual cycle, blood samples for AMH and other hormones were collected. On the same day, antral follicle count (AFC), and ovarian volumes were measured. A multiple regression analysis was carried out to examine the contribution of factors to the serum AMH levels in patients with psoriasis. The serum AMH levels and ovarian volumes were lower in the psoriasis group than in the control group (1.85 ± 1.13 ng/ml vs 2.46 ± 1.21 ng/ml, p = .029 and 10.43 ± 3.08 cm3 vs 11.93 ± 3.01 cm3, p = .038). However, the mean AFC between the two groups was not significantly different. The psoriasis area severity index (PASI) score did not correlate with AMH. On the other hand, the duration of the disease negatively correlated with AMH, total AFC and ovarian volume. In the multiple regression analysis, duration of disease and total AFC were the most significant contributors to the serum AMH levels in patients with psoriasis. Autoimmune diseases may affect ovarian reserve regardless of immunosuppresive treatment. Longitudinal follow-ups regarding reproductive function might be required in women with psoriasis.

Photodynamic Therapy with Hexa(sulfo-n-butyl)[60]Fullerene Against Sarcoma In Vitro and In Vivo.

The hydrophilic molecular micellar hexa(sulfo-n-butyl)[60]fullerene (FC4S), first synthesized in 1998 as a photosensitizer (PS) has been reported to exhibit high efficacy for singlet oxygen generation and antimicrobial photodynamic inactivation. The purpose of this study was to investigate the effects of photoactivated FC4S for free radical generation and to mediate photodynamic therapy (PDT) of cancer in vitro and in vivo. The results demonstrated that following light irradiation, FC4S produced singlet oxygen, but after addition of electron donors such as ferrocytochrome c or NADH, FC4S also produced superoxide. The combination of FC4S with light irradiation was able to induce cytotoxicity to human fibrosarcoma cells and murine sarcoma 180 cells in vitro. Cell-killing was proportional to fluence as well as FC4S concentration. Photoirradiation by argon-ion laser after intraperitoneal injection of FC4S also resulted in inhibition of S180 tumor growth in vivo (up to 80% reduction of tumor volume). Hematological and blood biochemistry parameters of the cancer-bearing mice were improved by PDT. Based on these findings, we conclude that FC4S has a great potential as a nanomedicine in PDT for cancer.

Bacterial photodynamic inactivation mediated by methylene blue and red light is enhanced by synergistic effect of potassium iodide.

The inexorable increase of antibiotic resistance occurring in different bacterial species is increasing the interest in developing new antimicrobial treatments that will be equally effective against multidrug-resistant strains and will not themselves induce resistance. One of these alternatives may be photodynamic inactivation (PDI), which uses a combination of nontoxic dyes, called photosensitizers (PS), excited by harmless visible light to generate reactive oxygen species (ROS) by type 1 (radical) and type 2 (singlet oxygen) pathways. In this study, we asked whether it was possible to improve the efficacy of PDI in vitro and in vivo by addition of the inert salt potassium iodide (KI) to a commonly investigated PS, the phenothiazinium dye methylene blue (MB). By adding KI, we observed a consistent increase of red light-mediated bacterial killing of Gram-positive and Gram-negative species in vitro and in vivo. In vivo, we also observed less bacterial recurrence in wounds in the days posttreatment. The mechanism of action is probably due to formation of reactive iodine species that are produced quickly with a short lifetime. This finding may have a relevant clinical impact by reducing the risk of amputation and, in some cases, the risk of death, leading to improvement in the care of patients affected by localized infections.

T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?

Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients.

Low-level laser (light) therapy (LLLT) for treatment of hair loss.

OBJECTIVE: Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia, the most common type, affects 50% of males over the age of 40 and 75% of females over 65. Only two drugs have been approved so far (minoxidil and finasteride) and hair transplant is the other treatment alternative. This review surveys the evidence for low-level laser therapy (LLLT) applied to the scalp as a treatment for hair loss and discusses possible mechanisms of actions. METHODS AND MATERIALS: Searches of PubMed and Google Scholar were carried out using keywords alopecia, hair loss, LLLT, photobiomodulation. RESULTS: Studies have shown that LLLT stimulated hair growth in mice subjected to chemotherapy-induced alopecia and also in alopecia areata. Controlled clinical trials demonstrated that LLLT stimulated hair growth in both men and women. Among various mechanisms, the main mechanism is hypothesized to be stimulation of epidermal stem cells in the hair follicle bulge and shifting the follicles into anagen phase. CONCLUSION: LLLT for hair growth in both men and women appears to be both safe and effective. The optimum wavelength, coherence and dosimetric parameters remain to be determined.

Photodynamic therapy with decacationic [60]fullerene monoadducts: effect of a light absorbing electron-donor antenna and micellar formulation.

We report the synthesis and anticancer photodynamic properties of two new decacationic fullerene (LC14) and red light-harvesting antenna-fullerene conjugated monoadduct (LC15) derivatives. The antenna of LC15 was attached covalently to C60>with distance of only <3.0 Ǻ to facilitate ultrafast intramolecular photoinduced-electron-transfer (for type-I photochemistry) and photon absorption at longer wavelengths. Because LC15 was hydrophobic we compared formulation in Cremophor EL micelles with direct dilution from dimethylacetamide. LC14 produced more (1)O2 than LC15, while LC15 produced much more HO·than LC14 as measured by specific fluorescent probes. When delivered by DMA, LC14 killed more HeLa cells than LC15 when excited by UVA light, while LC15 killed more cells when excited by white light consistent with the antenna effect. However LC15 was more effective than LC14 when delivered by micelles regardless of the excitation light. Micellar delivery produced earlier apoptosis and damage to the endoplasmic reticulum as well as to lysosomes and mitochondria. FROM THE CLINICAL EDITOR: This team of authors report the synthesis and the photodynamic properties of two new derivatives for cancer treatment; one is a decacationic fullerene (LC14) and the other is a red light-harvesting antenna-fullerene conjugated monoadduct (LC15) utilizing a HeLa cell model.

Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology.

BACKGROUND: Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood. METHODS: To address this issue, we used a systems biology approach utilizing NASA's Open Science Data Repository (OSDR) on space flown murine transcriptomic datasets focused on the skin, biochemical profiles of 50 NASA astronauts and human transcriptomic datasets generated from blood and hair samples of JAXA astronauts, as well as blood samples obtained from the NASA Twins Study, and skin and blood samples from the first civilian commercial mission, Inspiration4. RESULTS: Key biological changes related to skin health, DNA damage & repair, and mitochondrial dysregulation are identified as potential drivers for skin health risks during spaceflight. Additionally, a machine learning model is utilized to determine gene pairings associated with spaceflight response in the skin. While we identified spaceflight-induced dysregulation, such as alterations in genes associated with skin barrier function and collagen formation, our results also highlight the remarkable ability for organisms to re-adapt back to Earth via post-flight re-tuning of gene expression. CONCLUSION: Our findings can guide future research on developing countermeasures for mitigating spaceflight-associated skin damage.

Spaceflight is a hostile environment which can lead to health problems in astronauts, including in the skin. It is not currently well understood why these skin problems occur. Here, we analyzed data from the skin of space flown mice and astronauts to try and identify possible explanations for these skin problems. It appears that changes in the activation of genes related to damage to DNA, skin barrier health, and mitochondria (the energy-producing parts of cells) may play a role in these skin problems. Further research will be needed to confirm exactly how these changes influence skin health, which could lead to solutions for preventing and managing such issues in astronauts.

Melanoma resistance to photodynamic therapy: new insights.

Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested in the treatment of melanoma with some promising results, but melanoma is generally considered to be resistant to it. Optical interference by the highly-pigmented melanin, the antioxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700-800-nm near infrared spectral region; interventions that can temporarily reduce the amount or pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system against the tumor being treated.

Low-level laser therapy for fat layer reduction: a comprehensive review.

BACKGROUND AND OBJECTIVE: Low-level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction. MATERIALS AND METHODS: A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre-clinical and clinical studies with respect to the mechanism of action, efficacy, and safety. RESULTS: The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids. CONCLUSION: Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand-alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action.

Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring.

Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require stimulation of healing, relief of pain and inflammation, and restoration of function. Although skin is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths. The photons are absorbed by mitochondrial chromophores in skin cells. Consequently, electron transport, adenosine triphosphate nitric oxide release, blood flow, reactive oxygen species increase, and diverse signaling pathways are activated. Stem cells can be activated, allowing increased tissue repair and healing. In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a treatment and as a prophylactic measure. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also be managed. The noninvasive nature and almost complete absence of side effects encourage further testing in dermatology.

Scrofuloderma and granuloma annulare-like lesions: Challenges of diagnosing cutaneous tuberculosis in developed countries.

Tuberculosis remains a global health concern, as the increasing levels of urban poverty, higher number of immunodeficient patients and the development of drug resistance threaten the overall efforts made to induce a downward trend for the disease. Scrofuloderma, also known as tuberculosis cutis colliquativa is a subtype of cutaneous tuberculosis. Here we detail a case of a 70-year-old female patient presented with unilateral, left-sided, multiple palpable, painful, ulcerated and purulent cervical nodules, accompanied by persistent generalized erythematous popular granuloma annulare-like skin lesions on the upper extremities. Based on the result of the PCR assay, culture, imaging and histopathological findings, the diagnosis of scrofuloderma was established. To achieve prompt diagnosis and early treatment, it is crucial to include scrofuloderma in the differential diagnosis of ulcerated lesions in developed countries as well, and also be aware of the additional clinical symptoms, such as granuloma annulare-like lesions, possibly accompanying cutaneous tuberculosis.

Clinicians' pearls and myths in pemphigus.

Pemphigus comprises a heterogeneous group of autoimmune blistering diseases, which can affect both skin and mucous membranes, especially oral mucosa. This group of diseases shows usually a chronic-relapsing course. Since pemphigus is a rare disease, the diagnosis is often delayed, because it is based upon the recognition of consistent clinical, histologic, and direct immunofluorescence findings, as well as indirect immunofluorescence, and/or enzyme-linked immunosorbent assay. Usually the patients are treated for multiple other conditions before starting the correct therapy, leading to a critical reduction of the patients' quality of life. This review is a succinct compilation of pearls gathered from clinical experience in pemphigus and the myths that may have influenced everyday practice but have been proven false. This review provided a selection of such dilemmas and controversies, focusing on myths and pearls that can help young dermatologist in the clinic, while also dispelling them.

Machine Learning Based Prediction of Squamous Cell Carcinoma in Ex Vivo Confocal Laser Scanning Microscopy.

Image classification with convolutional neural networks (CNN) offers an unprecedented opportunity to medical imaging. Regulatory agencies in the USA and Europe have already cleared numerous deep learning/machine learning based medical devices and algorithms. While the field of radiology is on the forefront of artificial intelligence (AI) revolution, conventional pathology, which commonly relies on examination of tissue samples on a glass slide, is falling behind in leveraging this technology. On the other hand, ex vivo confocal laser scanning microscopy (ex vivo CLSM), owing to its digital workflow features, has a high potential to benefit from integrating AI tools into the assessment and decision-making process. Aim of this work was to explore a preliminary application of CNN in digitally stained ex vivo CLSM images of cutaneous squamous cell carcinoma (cSCC) for automated detection of tumor tissue. Thirty-four freshly excised tissue samples were prospectively collected and examined immediately after resection. After the histologically confirmed ex vivo CLSM diagnosis, the tumor tissue was annotated for segmentation by experts, in order to train the MobileNet CNN. The model was then trained and evaluated using cross validation. The overall sensitivity and specificity of the deep neural network for detecting cSCC and tumor free areas on ex vivo CLSM slides compared to expert evaluation were 0.76 and 0.91, respectively. The area under the ROC curve was equal to 0.90 and the area under the precision-recall curve was 0.85. The results demonstrate a high potential of deep learning models to detect cSCC regions on digitally stained ex vivo CLSM slides and to distinguish them from tumor-free skin.

Significance of validation for karst aquifers' vulnerability assessments: Antalya Travertine Plateau (Turkey) application.

Vulnerability maps were generated for Altinova Region within the Antalya Travertine Plateau based on DRASTIC, SINTACS, EPIK, COP and PI methods. Majority of the study area is covered by productive karstic aquifer, which is composed of travertine. Travertine includes typical karstic features such as dolines, springs and caves where groundwater of travertine aquifer is the sole source for irrigation. Areal extends of low, medium, high and very high vulnerability classes and their areal extends were determined for all methods and compared with each other. High and very high vulnerable areas covered >74% of the study area as investigated by all methods, except PI. Although PI is a specific method for karstic aquifers, this method could not generate a reasonable vulnerability map based on the assigned parameter definitions and scores. Only areal extents were not sufficient to decide about the proper vulnerability method for the study area. Therefore, NO3- concentration based validation method was performed for all generated vulnerability maps. Consequently, the areas which had NO3- concentrations higher than 30 mg/L were matched with high-very high vulnerable areas. According to this validation method, application of SINTACS with "karstic aquifer" weights could validate 95% of the area with NO3- concentrations higher than the selected threshold level of 30 mg/L for Altinova region. This study showed that simulation performance of vulnerability methods was highly related to the defined parameter definitions, score ranges and weights of each method. Similar parameters with variable score ranges could create considerably distinct vulnerability maps. Validation is the essential interpretation step for taking decision on the proper vulnerability method. Additionally, site-specific contaminant observations are critical for validation of vulnerability maps. Validated vulnerability maps could be used as a valuable water resources management tool.