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A letter to the editor is presented that discusses dermoscopy of drug-induced aquagenic wrinkling phenomenon.

Background: The introduction of targeted therapies for the treatment of BRAF-mutated metastatic melanoma was associated with different cutaneous adverse events (AEs)., Objectives: To describe the type, frequency and severity of cutaneous AEs related to vemurafenib; to understand the association between AEs and vemurafenib efficacy in terms of median overall survival (OS) and median progression-free survival (PFS); to identify molecular characteristics of long-term responders., Methods: This observational, retrospective, monocentric study included all consecutive patients with unresectable stage III or stage IV melanoma and BRAF V600E mutation that started treatment with vemurafenib between May 2012 and May 2014., Results: 62 patients with a median age of 56 years (range 26-82) were enrolled and received vemurafenib for a median period of 7.9 months (range 0.8-63.7). Among them, 45 patients presented at least one skin AE, 12 reduced the dosage due to cutaneous toxicity, and only one firstly reduced and after stopped the therapy. No specific molecular biomarkers were detected in long-term survivors., Conclusions: Among long-term survivors, skin AEs seem to be less frequent and less severe. Results on multivariable analysis revealed that the presence of at least one G2 toxicity is a protective factor considering PFS, but not in terms of OS.

Cystic echinococcosis (CE) is one of the most important zoonotic diseases. The primary treatment is surgery and chemical sterilization of the parasitic layers by injection of a scolicidal agent. Available scolicidals possess side effects, and may cause postoperative complications. Several studies reported the scolicidal properties of monoterpene phenols and alcohols such as carvacrol, thymol, and geraniol. The present study aimed to develop, characterize, and assess monoterpene loaded microemulsions as novel green scolicidals products. For this purpose, microemulsions composing 0.37%, 0.75%, and 1.5% of monoterpenoid(s), thymol, carvacrol, and geraniol, alone or in binary or ternary mixtures were formulated. Samples were analyzed by visual inspection, polarizing optical microscope, and dynamic light scattering (DLS). The stability of the samples was evaluated up to a 3-month storage. For the scolicidal bioassay, samples at different concentrations of 200, 100, 50, 25, and 10 μg/ml were added to wells containing 10 4 viable protoscoleces and mortality rates were recorded at 2, 5, 10, and 20 min after exposure. Results of the present study showed that microemulsions formulated with 0.75% of pure carvacrol or the binary mixture of thymol and carvacrol at 0.375% are promising scolicidal agents., (© 2021 Wiley Periodicals LLC.)

Background: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions., Objectives: To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders., Materials & Methods: Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases., Results: No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error., Conclusion: Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

The growing interest in the development of green pest management strategies is leading to the exploitation of essential oils (EOs) as promising botanical pesticides. In this respect, nanotechnology could efficiently support the use of EOs through their encapsulation into stable nanoformulations, such as nanoemulsions (NEs), to improve their stability and efficacy. This technology assures the improvement of the chemical stability, hydrophilicity, and environmental persistence of EOs, giving an added value for the fabrication of natural insecticides effective against a wide spectrum of insect vectors and pests of public and agronomical importance. Carlina acaulis (Asteraceae) root EO has been recently proposed as a promising ingredient of a new generation of botanical insecticides. In the present study, a highly stable C. acaulis -based NE was developed. Interestingly, such a nanosystem was able to encapsulate 6% ( w / w ) of C. acaulis EO, showing a mean diameter of around 140 nm and a SOR (surfactant-to-oil ratio) of 0.6. Its stability was evaluated in a storage period of six months and corroborated by an accelerated stability study. Therefore, the C. acaulis EO and C. acaulis -based NE were evaluated for their toxicity against 1st instar larvae of the European grapevine moth (EGVM), Lobesia botrana (Denis & Schiffermüller, 1775) (Lepidoptera: Tortricidae), a major vineyard pest. The chemical composition of C. acaulis EO was investigated by gas chromatography-mass spectrometry (GC-MS) revealing carlina oxide, a polyacetylene, as the main constituent. In toxicity assays, both the C. acaulis EO and the C. acaulis -based NE were highly toxic to L . botrana larvae, with LC 50 values of 7.299 and 9.044 µL/mL for C. acaulis EO and NE, respectively. The C. acaulis -based NE represents a promising option to develop highly stable botanical insecticides for pest management. To date, this study represents the first evidence about the insecticidal toxicity of EOs and EO-based NEs against this major grapevine pest.

Among the various innovative products obtainable from hemp ( Cannabis sativa L.) waste biomass originating from different industrial processes, the essential oil (EO) deserves special attention in order to understand its possible application in different fields, such as cosmetics, pharmaceuticals, and botanical insecticides. For the purpose, in the present work, we studied the chemical composition of EOs obtained from different hemp varieties, namely Felina 32 and Carmagnola Selezionata (CS) using monoecious, male, and female inflorescences, and we evaluated their mosquitocidal activities on larvae and pupae of two main malaria vectors, Anopheles gambiae and An. stephensi . Then, in order to evaluate the safe use of hemp EOs for operators, the potential pro- or anti-inflammatory effect of hemp EOs together with their toxicological profile were determined on dermal fibroblasts and keratinocytes. Given the promising results obtained by insecticidal and anti-inflammatory studies, a preliminary evaluation of EOs encapsulation into nanoemulsions (NEs) has been performed with the aim to develop a formulation able to improve their poor physicochemical stability. Felina 32 and CS inflorescences provided EOs with an interesting chemical profile, with monoterpene and sesquiterpene hydrocarbons as the major components. This study highlighted the potential application of male inflorescences, which are usually discharged during hemp product processing. These EOs could be exploited as potential sustainable and eco-friendly insecticides, given their capability to be toxic against mosquitoes and the possibility to use them to prepare stable and safe formulations. The LC 50 values found in this study (<80 ppm) are lower, on average, than those of many plant EOs, with the advantage of using an industrial waste product. From MTT assay and gene and protein expression analysis, EOs showed no cytotoxicity at the appropriate doses and exerted an anti-inflammatory effect on the human cell lines tested. These findings encourage further applied research on hemp EOs in order support their industrial exploitation.

The interest around essential oils is constantly increasing thanks to their biological properties exploitable in several fields, from pharmaceuticals to food and agriculture. However, their widespread use and marketing are still restricted due to their poor physico-chemical properties; i.e., high volatility, thermal decomposition, low water solubility, and stability issues. At the moment, the most suitable approach to overcome such limitations is based on the development of proper formulation strategies. One of the approaches suggested to achieve this goal is the so-called encapsulation process through the preparation of aqueous nano-dispersions. Among them, micro- and nanoemulsions are the most studied thanks to the ease of formulation, handling and to their manufacturing costs. In this direction, this review intends to offer an overview of the formulation, preparation and stability parameters of micro- and nanoemulsions. Specifically, recent literature has been examined in order to define the most common practices adopted (materials and fabrication methods), highlighting their suitability and effectiveness. Finally, relevant points related to formulations, such as optimization, characterization, stability and safety, not deeply studied or clarified yet, were discussed.

We report a case of a healthy 26-year-old male with multiple asymptomatic reddish papules and papule-nodules on the central area of the face, persisting from more than 2 months and gradually increasing in number. An incisional skin biopsy revealed a confluent dense granulomatous infiltrate centred by large areas of eosinophilic necrosis consistent with the diagnosis of lupus miliaris disseminatus faciei (LMDF). This is a rare dermatosis first described in 1878 by Fox, that often poses a clinical challenge as it is a disease process which is difficult to diagnose. In fact, in our case, a diagnosis of LMDF was made on skin biopsy. We think that collaboration among dermatologists and General Practitioners is very important for diagnosis of rare dermatosis and especially for management of it, in order to prevent the development of depressed scars.

The management of parasites, insect pests and vectors requests development of novel, effective and eco-friendly tools. The development of resistance towards many drugs and pesticides pushed scientists to look for novel bioactive compounds endowed with multiple modes of action, and with no risk to human health and environment. Several natural products are used as alternative/complementary approaches to manage parasites, insect pests and vectors due to their high efficacy and often limited non-target toxicity. Their encapsulation into nanosystems helps overcome some hurdles related to their physicochemical properties, for instance limited stability and handling, enhancing the overall efficacy. Among different nanosystems, micro- and nanoemulsions are easy-to-use systems in terms of preparation and industrial scale-up. Different reports support their efficacy against parasites of medical importance, including Leishmania , Plasmodium and Trypanosoma as well as agricultural and stored product insect pests and vectors of human diseases, such as Aedes and Culex mosquitoes. Overall, micro- and nanoemulsions are valid options for developing promising eco-friendly tools in pest and vector management, pending proper field validation. Future research on the improvement of technical aspects as well as chronic toxicity experiments on non-target species is needed.

Hydrocolloids have been intensively investigated due to their ability to modify the rheology of the system where they are employed. They find application as thickening and gelling agents in many food, cosmetic, and pharmaceutical preparations, due to their biocompatibility and biodegradability. The present study aims to provide an exhaustive and comprehensive viscoelastic characterization of a series of hydrocolloid formulations, as function of concentration, pH, and temperature. Glucomannan, xanthan gum, tara gum, guar gum, konjac gum, and gellan gum have been analyzed at two concentrations (0.5% w/w and 1.5% w/w), using three different pH conditions (pH 1.2, 5.5, and 6.8). Their viscoelastic properties have been monitored measuring the main rheological parameters, namely, storage modulus G' and loss modulus G'' as function of frequency, time, and temperature. The results obtained show a clear dependence of the linear viscoelastic properties of the systems on concentration and pH, while the temperature was not a critical factor. Glucomannan, xanthan gum, tara gum, and guar gum samples prepared in phosphate buffer (pH 6.8) at the final concentration of 1.5% (w/w) have been selected as the most promising systems for further investigations, exploring the possibility of combinations to improve the rheological properties. PRACTICAL APPLICATION: Glucomannan, xanthan gum, tara gum, guar gum, konjac gum, and gellan gum have been chosen among the most common thickening agents derived from plants to perform a systematic investigation of the influence of pH, concentration, and temperature on the rheological properties of their water dispersions. The data obtained may be useful for further application of these hydrogels in the nutraceutical field as thickeners, texture modifiers, emulsifiers, stabilizers, and gelling agents., (© 2018 Institute of Food Technologists®.)

Tablets disintegration is often the result of a size expansion of the tablets. In this study, we quantified the extent and direction of size expansion of tablets during disintegration, using readily available techniques, that is, a digital camera and public domain image analysis software. After validating the method, the influence of disintegrants concentration and diluents type on kinetics and mechanisms of disintegration were studied. Tablets containing diluent, disintegrant (sodium starch glycolate, crospovidone, or croscarmellose sodium), and lubricant were prepared by direct compression. Projected area and aspect ratio of the tablets were monitored using image analysis techniques. The developed method could describe the kinetics and mechanisms of disintegration qualitatively and quantitatively. Sodium starch glycolate and crospovidone acted purely by swelling and shape recovery mechanisms. Instead, croscarmellose sodium worked by a combination of both mechanisms, the extent of which changed depending on its concentration and the diluent type. We anticipate that the method described here could provide a framework for the routine screening of tablets disintegration using readily available equipment., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Among older patients, melanoma in general presents biological features related to a more aggressive biology, such as more locally advanced tumor. Management of melanoma in elderly may be difficult, mainly due to comorbidities. We report the experience of the Melanoma Unit of ASST Spedali Civili in Brescia, Italy., Methods: Study subjects were drawn from 3444 patients with histological confirmed melanoma. Data were extracted from electronic database of the Melanoma Unit of ASST Spedali Civili in Brescia, Italy. Patients who received diagnosis of cutaneous melanoma at age of 65 years or older were retrospectively evaluated. For each diagnosed melanoma, histological characteristics, treatment, and outcomes were evaluated., Results: Of the 805 patients described in this study, 444 were males and 361 females. Statistically significant differences were found between patients aged 65-80 years and those aged >80 years considering melanoma prognostic factors, such as Breslow thickness, number of mitoses/mm2 and ulceration., Conclusions: Older age is recognized as an independent poor prognostic factor in melanoma patients, and melanoma in older patients have a distinct natural history. It was found that management of cancer in old person represents a major challenge to medical practice. We believe that the choice of therapy should be individualized and based upon the individual's overall health and that, particularly in these cases, management often requires interdisciplinary cooperation between dermatologist, surgical specialist, oncologist and geriatrician.

Genetic susceptibility to primary cutaneous melanoma (PCM) may account for up to 12% of PCMs, presenting as the familial atypical mole/multiple melanoma syndrome (FAMMM), an autosomal dominant condition with incomplete penetrance and variable expressivity, characterized by PCM in at least two relatives and/or more than one PCMs in the same patient. To identify individuals at high genetic risk of PCM, from 1 January 2012 to 31 December 2015, we offered genetic counselling and molecular analysis of the two high-penetrance FAMMM susceptibility genes, cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase 4 (CDK4), to 92 consecutive, unrelated patients with FAMMM. Age at diagnosis and number of PCMs were obtained from medical records; the number of PCMs and affected relatives were recorded for each family. The diagnostic work-up consisted of genetic counselling and cascade genetic testing in patients and further extension to relatives of those identified as mutation carriers. All exons and exon/intron boundaries of CDKN2A and CDK4 genes were screened by direct bidirectional sequencing. We identified CDKN2A mutations in 19 of the 92 unrelated patients (20.6%) and in 14 additional, clinically healthy relatives. Eleven of these latter subsequently underwent excision of dysplastic nevi, but none developed PCM during a median follow-up of 37.3 months. In three patients from unrelated families, the novel CDKN2A p.D84V (c.251A>T) mutation was observed, associated with PCM in each pedigree. Genetic screening of FAMMM patients and their relatives can contribute towards specific primary and secondary prevention programmes for individuals at high genetic risk of PCM. The novel CDKN2A p.D84V (c.251A>T) mutation adds to the known mutations associated with FAMMM.

Aim: Skin self-examination is usually recommended for early melanoma diagnosis. Given the current lack of a standardized Skin Self-Examination method, we raised the issue about the suitable approach to explain to patients what can be considered a suspicious lesion. Hereinafter, we report the results of a pilot-study carried out at the Melanoma Centre, University Hospital Spedali Civili Brescia, Italy., Methods: A consecutive sample of 200 melanoma patients entered into the Melanoma Prevention Project. A detailed survey revealed who had the first suspicion of the melanoma lesion. When melanoma was Self- or Relative-detected, we investigated the signs/symptoms that had alerted patients with reference to the ABCDE rule. The study included also socio-demographic variables, family history of melanoma, skin type, number and type of nevi, and melanoma features., Results: Eighty-seven melanoma had been Self-Detected and 44 Relative-Detected. Patients report most commonly signs/symptoms such as dark colour (58%) and changing in size (47%). Seventy-nine percent of these patients have less than ten nevi and 92% have small and regular moles., Conclusion: Sometimes the signs of melanoma seem to be easy to identify. Our patients say that they recognized melanoma on the base of the Colour and the Change in size. Therefore, we propose the short "CC" acronym that could facilitate the melanoma self-diagnosis. The aim is to give a short and effective message that leads patients to have the doubt of a suspicious lesion of melanoma so that they seek medical attention.

Background: The relationship between the occurrence of skin diseases and skin tattoos remains unclear. Dermatologic disorders have been reported to occur in about 2% of cases. In addition, tattoo pigment can migrate to the regional lymph nodes through the lymphatic vessels and subsequently mimic metastatic disease from melanoma., Methods: A 23-year-old Caucasian man presented with a pigmented lesion on the left scapular region, which had slowly enlarged over time. The patient exhibited an extensive tattoo on the left upper arm, left shoulder, and part of the upper back. His medical history was unremarkable. The pigmented lesion was excised. Histology confirmed malignant melanoma. Ultrasound examination of the abdomen, neck, and inguinal and axillary lymph nodes and a total body computed tomography scan showed no sign of disease. A re-excision with 2-cm margins and sentinel lymph node biopsy (SLNB) were performed. Two grossly enlarged, black sentinel lymph nodes (SLNs) highly suggestive of melanoma metastases were removed., Results: No evidence of melanoma metastasis was found in any of the sampled tissues. Large amounts of pigment were present within the subcapsular space and sinusoid areas of the two clinically suspicious lymph nodes. Immunohistochemical analysis was negative., Conclusions: Sentinel lymph node biopsy is widely performed in cutaneous melanoma. Histologic confirmation of any enlarged, pigmented SLN is essential prior to radical surgery, especially when pigmented SLNs are found near a tattoo. Tattoo pigments may deposit in the regional lymph nodes and may clinically mimic metastatic disease. A history of tattooing should be considered in all melanoma patients eligible for SLNB. In a finding of darkly pigmented nodes during SLNB, radical lymphadenectomy should be withheld until immunohistologic confirmation of metastasis in the SLN is obtained., (© 2013 The International Society of Dermatology.)

Classically, dermatofibrosarcoma protuberans (DFSP) is a disease of adults. The world literature revision shows that several pediatric cases have been reported so far; this might suggest that the number of infants with the condition might be larger than that estimated previously. Here, we report the 183rd case of histologically confirmed DFSP in young age. A 14-year-old white male patient came under our care for a slowly growing, pale brownish lesion on the neck skin. A biopsy specimen showed a DFSP. Subsequently, a wide surgery excision with 3 cm of resection margins including the underlying fascia was performed. To date, the patient has been in follow-up for 6 years without evidence of recurrent disease. The clinical features and treatment of DFSP diagnosed in childhood and adolescence reported in the published literature are reviewed to provide new insights about this rare entity. The aim is to emphasize the importance of biopsy for histologic evaluation in the cases that show a persistent or a large cutaneous plaque or nodule without pathognomonic clinical features that permit a clinical diagnosis. An accurate knowledge of the disease is the prerequisite for a wider recognition and appropriate treatment.

Aim: A giant congenital nevus is a melanocytic nevus present at birth with wide extent on the skin surface. The management of this nevus remains controversial and needs to be personalized for each patient., Methods: A retrospective multicenter study was carried out in the Dermatological Departments of Brescia, Padua, and Pavia, Italy. The inclusion criterion was the diagnosis of a giant congenital melanocytic nevus on the basis of clinical observation., Results: Nine patients with giant congenital nevus are reported. None developed melanoma, whereas giant congenital nevi have been slowly fading in pigmentation., Conclusion: Having regard to the doubts on treatment that persist in the literature, we should consider that decisional management of giant congenital melanocytic nevi can be really complex, because of the size and depth of lesions. Indeed, the ablative surgery or other treatments might cause significant troubles and complete excision of deeper layers of the lesion is almost impossible to achieve. Moreover, the treatment does not reduce the risk of melanoma and might lead to a greater difficulty in clinical and dermoscopic observation due to the scarring occurrence after therapy. In our retrospective study, the pigmentation of giant congenital melanocytic nevi slowly faded on its own and until now none developed melanoma. Therefore, we suggest a close regular follow-up which should be focused on the exclusion of possible complications. Perhaps, it would be better "to wait and see" since other procedures do not decrease the risk of melanoma, but rather might lead the patient to underestimate it.