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AIM: In this paper, inspiring Darwin’s theory, we propose a model which connects evolutions of neural circuits with evolutions of cosmos. In this model, in the beginning, there are some closed strings which decay into two groups of open strings. METHODS: First group couple to our universe from one side and produce matters like some genes of DNAs and couple to an anti-universe from another side with opposite sign and create anti-matters like some anti-genes of anti-DNAs. Second group couple to the star and planet’s cores like the earth’s core from one side and produce anti-matters like stringy black anti-DNA and couple to outer layers of stars and planets like the earth from other side and produce matters like some genes of DNAs on the earth. Each DNA or anti-DNA contains some genetic circuits which act like the circuits of receiver or sender of radio waves. To transfer waves of these circuits, some neurons emerge which some of them are related to genetic circuits of anti-DNAs in anti-universe, and some are related to genetic circuits of stringy black anti-DNA within the earth’s core. A collection of these neural circuits forms the little brain on the heart at first and main brain after some time. RESULTS: To examine the model, we remove effects of matters in outer layers of earth in the conditions of microgravity and consider radiated signals of neural circuits in a chick embryo. We observe that in microgravity, more signals are emitted by neural circuits respect to normal conditions. This is a signature of exchanged waves between neural circuits and structures within the earth’s core. CONCLUSION: These communications help some animals to predict the time and place of an earthquake.

To recover chick embryos damaged the brain, two methods are presented. In both of them, somatic cells of an embryo introduced into an egg cell and an embryo have emerged. In one method, injured a part of the brain in the head of an embryo is replaced with a healthy part of the brain. In the second method, the heart of brain embryo dead is transplanted with the embryo heart. In this mechanism, new blood cells are emerged in the bone marrow and transmit information of transplantation to subventricular zone (SVZ) of the brain through the circulatory system. Then, SVZ produces new neural stem cells by a subsequent dividing into neurons. These neurons produce new neural circuits within the brain and recover the injured brain. To examine the model, two hearts of two embryos are connected, and their effects on neural circuits are observed.

Vitiligo is an important skin disease of childhood. The authors briefly discuss the etiopathobiology, clinics and comorbidities of the disease.

BACKGROUND: Postmenopausal women experience undesired symptoms that adversely affect their quality of life. In the recent years, a specific 12 - week fractional CO2 laser treatment has been introduced, with highly significant relief of symptoms.AIM: The aim of this paper is the identification of the early modifications of structural components of atrophic vaginal mucosa induced by laser irradiation, which is responsible for the restorative processes.MATERIAL AND METHODS: We investigated by microscopical, ultrastructural and biochemical methods the modifications of the structural components of postmenopausal atrophic vaginal mucosa tissues after 1 hour following a single fractional laser CO2 application.RESULTS: In one hour, the mucosal epithelium thickens, with the maturation of epithelial cells and desquamation at the epithelial surface. In the connective tissue, new papillae indenting the epithelium with newly formed vessels penetrating them, new thin fibrils of collagen III are also formed in a renewed turnover of components due to the increase of metalloproteinase - 2. Specific features of fibroblasts support stimulation of their activity responsible of the renewal of the extracellular matrix, with an increase of mechanical support as connective tissue and stimulation of growth and maturation to epithelium thanks to new vessels and related factors delivered.CONCLUSION: We found the activation of regenerative mechanisms expressed both in the connective tissue - with the formation of new vessels, new papillae, and new collagen - and in the epithelium with the associated thickening and desquamation of cells at the mucosal surface.

Vitiligo is an acquired chronic hypopigmentary disorder, which usually stars in childhood. The Authors discuss a short review of the more innovative therapies for childhood vitiligo.

An overview of unconventional therapies for vitiligo is presented. Some herbal compounds may be considered as valid therapeutic tools for the treatment of vitiligo.

AIM: Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly characterized by painful, deep dermal abscesses and chronic draining sinus tracts. Recently, laser and light-based therapies have become more commonly used in the management of HS.MATERIAL AND METHODS: We report 20 HS patients treated with a 1064 nm wavelength, emitted from a diode laser, launched in an optical fibre through intracavitary modalities.RESULTS: Each patient underwent four laser sessions, one every two weeks. we recorded a significative reduction (31%) of Sartorius score from 28.55 ± 13.04 to 19.75 ± 12.29 after 4 laser sessions (p < 0.05). No one has had a worsening of the disease.CONCLUSION: Intralesional diode laser 1064 nm can be a good treatment option for patients with moderate and localized hidradenitis suppurativa, because it is minimally invasive, doesn’t have significant complications and provides a rapid post-treatment recovery.

The cutaneous dermatomycoses are among topical issues in all countries worldwide. They are registered in 20% of the world population. Dermatophyte infections incidence frequency varies depending on a season, region, effective anti-epidemic measures management, and effective treatment methods. In Kazakhstan in 2001, dermatophyte infections ranked second in the structure of dermatologic pathology in outpatients. According to the literature data, not so many research studies on dermatophyte infections have been carried out in our country within recent years. The importance of these issues suggests a need to conduct epidemiological, clinical, microbiological studies of dermatophytosis at the present stage. A cross-sectional study was conducted, in which 195 cases of dermatophytosis were collected and investigated in the regional hospital in Almaty for the period from the beginning of January 2014 to the end of December 2014. Dermatophytoses prevalence is observed in patients within the 1 - 39 age range.

Erythema ab igne is a localised, cutaneous condition consisting of reticulate hyperpigmentation, epidermal atrophy, and telangiectasias. It is caused by repetitive and prolonged exposure to moderate heat that is insufficient for producing burns. Currently, erythema ab igne is most commonly observed following repeated use of hot water bottles, infrared lamps and heating pads. If not properly treated, erythema ab igne can become chronic and even malignant. We report a case of erythema ab igne, successfully treated with systemic mesoglycan-based therapy, and local therapy with bioflavonoids.

BACKGROUND: Apitherapy is the medical use of honey bee products, "honey, propolis, royal jelly, bee wax, and bee venom to relieve human ailments. Propolis is one of the most well-documented products derived from the honeybee and has always played an important role in traditional folk medicine.AIM: The aim was to justify the consideration of Aloe Vera as an effective remedy for the treatment of psoriasis.METHODS: The study follows (857) patients (354 females, 503 males) with a mean age range from (9 - 62) years, affected with moderate to severe psoriasis in palms and foot soles treated by a combination mixture of propolis and Aloe in the form of an ointment (Aloreed) and Beauty reed cream. The treatment duration was for 12 weeks. Results were evaluated by using clinical, histological and statistical parameters.RESULTS: After the 12 - week treatment, we observed an 86% overall response rate from which 62% showed excellent results and 24% showed good results, therefore proving the efficiency in the use of the mixture of propolis 50% and aloe vera 3% as topically applied ointment in the treatment of mild to moderate psoriasisCONCLUSION: Patients who have palmoplantar psoriasis, who were treated with a topically applied mixture of propolis (50%) and aloe vera (3%), have shown noteworthy improvement thus proving the efficiency of propolis and aloe vera in the treatment of mild to moderate psoriasis.

The Authors discuss their experience in treating non-responder vitiligo patients with a UVA-1 laser. Laser Alba 355® is an innovative device of target UVA - 1 phototherapy. The present report suggests that UVA1 laser could be an applicable therapeutic option in patients with vitiligo, also for the ones who did not respond to the more conventional phototherapies.

Curcumin is a polyphenol derived from the golden spice turmeric, which is widely used for different purposes, such as culinary spice and alimentary addictive, make - up and, finally, as a natural product for the treatment of different diseases, especially for the chronic inflammatory ones. Recently, curcumin has been proposed as a valid and safe therapeutic option for psoriasis.

Firstly described by Robert Douglas Sweet in 1964, febrile neutrophilic dermatosis is a disabling, not only cutaneous disorder, clinically characterised by fever and painful erythematous nodules, with a typical background of neutrophilia. Sweet’s syndrome (SS) is a chronic inflammatory reactive disorder of unknown cause and incompletely established pathogenesis, although an interplay between genetic and environmental factors, including infections, is likely to occur. A significant part of cases has been demonstrated to be linked with malignancies, especially in the hematologic setting. Because of the underlying disease and related therapeutic measures, SS may present atypical clinical course, whereas the response to treatment is strictly dependent on the concurrent hematologic disease. Herein we describe a case of a lady who had a refractory form of SS, resulted in a paraneoplastic cutaneous disease, and AML. Surprisingly, clinical remission of SS followed cytotoxic chemotherapy while hematologic disorder obtained a further complete response.

Recently, some scientists from NASA have claimed that there may be a black hole like structure at the centre of the earth. We show that the existence of life on the earth may be a reason that this black hole like object is a black brane that has been formed from biological materials like DNA. Size of this DNA black brane is 109 times longer than the size of the earth's core and compacted interior it. By compacting this long object, a curved space-time emerges, and some properties of black holes emerge. This structure is the main cause of the emergence of the large temperature of the core, magnetic field around the earth and gravitational field for moving around the sun. Also, this structure produces some waves which act like topoisomerase in biology and read the information on DNAs. However, on the four-dimensional manifold, DNAs are contracted at least four times around various axis's and waves of earth couldn't read their information. While, by adding extra dimensions on 4 +n-dimensional manifold, the separation distance between particles increases and all of the information could be recovered by waves. For this reason, each DNA has two parts which one can be seen on the four-dimensional universe, and another one has existed in extra dimensions, and only it's e_ects is observed. This dark part of DNA called as a dark DNA in an extra dimension. These dark DNAs not only exchange information with DNAs but also are connected with some of the molecules of water and helps them to store information and have memory. Thus, the earth is the biggest system of telecommunication which connects DNAs, dark DNAs and molecules of water.

BACKGROUND: Recently, some new methods for sexing of chicken eggs by fluorescence and Raman spectroscopy through the shell membrane have been proposed. On the other hand, in another investigation, a new virus medical imaging has been suggested. AIM: In this research, summing over these considerations, a new technique for sexing of chicken eggs by virus spectroscopy through the shell membrane is proposed. METHODS: (Please, add text …) RESULTS: (Please, add text …) CONCLUSION: It is shown that viruses outside the shell of egg can communicate with materials inside it and determine the gender of chick embryo and its evolutions.

AIM: In this paper, using a mathematical model, we will show that for special exchanged photons, the Hamiltonian of a collection of neurons tends to a constant number and all activities is stopped. These photons could be called as the dead photons. To this aim, we use concepts of Bio-BIon in Izhikevich Neuron model. METHODS: In a neuron, there is a page of Dendrite, a page of axon's terminals and a tube of Schwann cells, axon and Myelin Sheath that connects them. These two pages and tube form a Bio-Bion. In a Bio-Bion, exchanging photons and some charged particles between terminals of dendrite and terminals of axon leads to the oscillation of neurons and transferring information. This Bion produces the Hamiltonian, wave equation and action potential of Izhikevich Neuron model. Also, this Bion determines the type of dependency of parameters of Izhikevich model on temperature and frequency and obtains the exact shape of membrane capacitance, resting membrane potential and instantaneous threshold potential. RESULTS: Under some conditions, waves of neurons in this BIon join to each other and potential shrinks to a delta function. Consequently, total Hamiltonian of the system tends to a constant number and system of neuron act like a dead system. Finally, this model indicates that all neurons have the ability to produce similar waves and signals like waves of the mind. CONCLUSION: Generalizing this to biology, we can claim that neurons out of the brain can produce signals of minding and imaging and thus mind isn’t confined to the brain.

Increasing incidence and poor outcome of chronic non-communicable diseases in western population would require a paradigm shift in the treatments. Guidelines-based medical approaches continue to be the standard rule in clinical practice, although only less than 15% of them are based on high-quality research. For each person who benefits from the 10 best-selling drugs in the USA, a number between 4 and 25 has no one beneficial effect. The reductionist linear medicine method does not offer solutions in the non-manifest preclinical stage of the disease when it would still be possible to reverse the pathological progression and the axiom "a drug, a target, a symptom" are still inconclusive. Needs additional tools to address these challenges. System Medicine considers the disease as a dysregulation of the biological networks that changes throughout the evolution of the pathological process and with the comorbidities development. The strength of the networks indicates their ability to withstand dysregulations during the perturbation phases, returning to the state of stability. The treatment of dysregulated networks before the symptomatological manifestation emerges offers the possibility of treating and preventing pathologies in the preclinical phase and potentially reversing the pathological process, stopping it or preventing comorbidities. Furthermore, treating shared networks instead of individual phenotypic symptoms can reduce drug use, offering a solution to the problem of ineffective drug use.

The first aids to burned patients are fundamental for the evolution of the disease and the success of the next medical care in a Burns Center. In our 30-years experience, we can reassume that they must be provided to limit the cause of thermal damage, to evaluate and correct eventual respiratory or cardiovascular disorders, to find out the possible damage to different organs and the primary care on cutaneous lesions.

Dermatosurgery and dermatooncology are an integral part of dermatology as a speciality, and this postulate is strictly respected in a high percentage of European dermatological units. Due to the fact that a number of other specialties interweave with the subject of therapy - the surgical treatment of the patient with skin tumors, the positioning of dermatosurgery as part of dermatology is generally controversial (according to some), and at the same time is often the subject of a number of debates and conflicts. These include maxillofacial surgeons, plastic surgeons, regenerative and reconstructive surgeons, surgical and medical oncologist, etc. The advantages of these specialities are mainly based on good medical practice and good surgical techniques that are applied. In contrast, their disadvantages are based on the lack of good awareness of the initial surgical approach as well as the need for time-adjusted and accurately performed additional surgical interventions which should befurthermore careful scheduled with the relevant oncology units. Losing this thread, in practice, it turns out that we are losing the patients themselves or, looking laconically, we are working with reduced efficiency and effectiveness. Although for the last 15 years the positions of these sub-sectors in Bulgaria had been underdeveloped, a certain ascent has been observed nowadays or from a couple of years ago. This advance is undoubtedly due to the influence of the German Dermatological School, presented by Prof. Dr. Uwe Wollina, Head of Department of Dermatology, Venereology and Allergology in Dresden, Germany, as well as due to other respected representative of the Italian Dermatological School - in the face of Prof. Dr. Torello Lotti, Head of the Dermatology Unit at G Marconi University of Rome, Italy.

BACKGROUND: Apitherapy is the medical use of honey bee products (honey, propolis, royal jelly, bee wax, and bee venom) to relieve human ailments, propolis in particularly, rich in essential oils such as flavonoid. Propolis is derived from tree buds and plants. It is considered as one of the most well-documented products from the honeybee and has always played an important role in traditional folk medicine. Another renowned plant is Aloe vera appertaining to the Liliaceae family. Its mucilaginous gel has been extensively used in many cultures for its apparent effectiveness in treating wounds, burns, itchiness and hair loss.AIM: The aim was to assess the efficacy of a mixture in an ointment form of propolis (50%) and aloe vera (3%), in the treatment of mild to moderate psoriasis.METHODS: In this double-blind control study, 2248 patients with both mild to moderate cases of psoriasis were evaluated from 2012 to 2015.RESULTS: In Group 1 the overall response at the end of 12 weeks was as follows: Cleared in 64.4% (excellent response), good response in 22.2%, and weak response in 5.6% and no response in 7.7%. In Group 2 (placebo group) no significant improvement was observed after 12 weeks of treatment. Also, histology also demonstrated a marked reduction in hyperkeratosis and acanthosis.CONCLUSION: In comparison with Group 2 (placebo group) patients in Group 1, treated with a mixture of propolis (50%) and aloe vera (3%), in the form of an ointment have shown noteworthy improvement thus substantiating the therapeutic value of propolis and aloe vera in the treatment of mild to moderate psoriasis.

Vitiligo is an important skin disease of childhood, which may lead to deep psychological trauma, resulting in a poor quality of life and low self-esteem. The Authors discuss a short review of the more conventional therapies available for the treatment of vitiligo in children.

Neauvia Intense is biocompatible, injectable hyaluronic acid (HA) filler PEG cross-linked for facial soft-tissue augmentation that provides volume to tissues. The aim of the present study is to evaluate the sensitivity of Neauvia Intense in hyaluronidase from bovine testes in a time-course analysis. The test is based on the colourimetric determination of the N-acetyl – D - glucosamine (NAG) released by the hyaluronidase in standardised conditions. The in vitro conditions involve the treatment of Neauvia Intense with a known concentration of the enzyme (6080U/ml). The NAG content was determined at different times to assess the kinetics of the degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h); the Ehrlich’s reagent was used for the colourimetric quantification, by the method described by Reissing and colleagues. The intensity of the violet colour developed after the chemical reaction was proportional to the NAG present in each sample. A microplate reader at 585 nm read the absorbance. The amount of NAG released by the product was proportional to the time of incubation with bovine hyaluronidase, reaching a plateau after 168 hours.

Despite the continuous introduction of innovative therapies for vitiligo, today none of them provide constant and excellent results in term of repigmentation. The authors report their experience in treating a localised form of vitiligo with a new protocol consisting in the use of a Fraxel Herbium laser, and in the following application of topical Latanoprost solution and, one day after, in lesional irradiation with UVA1 laser.

AIM: A multi - centre two years the long prospective open clinical study was conducted in five countries located in four different continents from May 2015 to evaluate the clinical safety and efficacy of Automatic Biofibre hair implant in male and female androgenetic alopecia. Biofibre®is a CE/TGA certified medical grade polyamide fibre suitable for implantation.MATERIAL AND METHODS: A total of 213 patients were enrolled in the study. Patients were assessed pre -operatively by Hamilton scale grading and the percentage of scalp covered by hair. All the patients underwent Biofibre hair implantation by a standardised surgical technique followed by adequate post-operative care. Efficacy of the implant was evaluated by surgeons and patients bimonthly for the first year and trimonthly during the second year. Any adverse effects were recorded during these visits.RESULTS: At the completion of the study period, a total of 194 patients concluded the trial and the results were statistically evaluated. Both Hamilton scale grading and covered area percent improved at the end of the study, and subjective and objective evaluations revealed satisfactory results. Side effects were reported in only 18 cases (9.27%) which were easily controlled by either topical or systemic treatment in 8 to 10 days.CONCLUSION: Overall a successful result was noticed in 97.94% of patients with great psychological satisfaction.

Health is a fundamental human right. The World Health Organization defines it as a "state of complete physical, psychological and social well - being and not merely the absence of disease or infirmity". The health of individuals, however, is also linked to the environment in which they live and especially to their ability to adapt and integrate into their life context. The relationship with the environment is extremely important because it is that interaction that outlines the concept of normality compared to pathology. Such normality needs to be contextualised by gender, geographical origin and by the individuals’ living conditions: as a matter of fact, what is normal for a young person may differ from what is normal for a senior one. That is to say, the concept of health is indeed relative and it is the result of an interesting evolution of the concept of illness. From the first approaches - dealing with the mere treatment of the symptoms - to the promise of a free-from-pain society, science and economics have played a significant role in redefining the dualism health/ illness. The article reflects on these two concepts, health and illness, in history and nowadays, and discusses the future of the medical science.

OBJECTIVE: Neauvia Stimulate is biocompatible, injectable hyaluronic acid (HA) filler (26 mg/ml) PEG crosslinked with 1% of calcium hydroxyapatite (CaHA) for facial soft-tissue augmentation that provides volume to tissues, followed by process of neocollagenesis for improving skin quality. AIM: The aim of the present study is to evaluate the biosafety of the product (Lot. 160517-26-1/2 PEG) on human keratinocytes cultured in vitro. MATERIAL AND METHODS: The experimental model proposed, despite being an in vitro system, allows the derivation of useful information to predict the possible activity of the product in further in vivo application. Human keratinocytes (HaCaT cells) were treated with the product for 24h at increasing concentrations of product respect to control (untreated cells). RESULTS: The biosafety of the product to be tested has been evaluated performing different methods: MTT test, NRU test, Kenacid Blue assay. Moreover, any possible effect on the structure, morphology, and viability of cells has been evaluated. CONCLUSION: In conclusion, the results obtained by the different methods show that the product Neauvia Stimulate® does not cause any cytotoxic effect and does not affect the correct structure and morphology of cells cultures. OBJECTIVE: Neauvia Stimulate is biocompatible, injectable hyaluronic acid (HA) filler (26 mg/ml) PEG crosslinked with 1% of calcium hydroxyapatite (CaHA) for facial soft-tissue augmentation that provides volume to tissues, followed by process of neocollagenesis for improving skin quality. AIM: The aim of the present study is to evaluate the biosafety of the product (Lot. 160517-26-1/2 PEG) on human keratinocytes cultured in vitro. MATERIAL AND METHODS: The experimental model proposed, despite being an in vitro system, allows the derivation of useful information to predict the possible activity of the product in further in vivo application. Human keratinocytes (HaCaT cells) were treated with the product for 24h at increasing concentrations of product respect to control (untreated cells). RESULTS: The biosafety of the product to be tested has been evaluated performing different methods: MTT test, NRU test, Kenacid Blue assay. Moreover, any possible effect on the structure, morphology, and viability of cells has been evaluated. CONCLUSION: In conclusion, the results obtained by the different methods show that the product Neauvia Stimulate® does not cause any cytotoxic effect and does not affect the correct structure and morphology of cells cultures.

OBJECTIVE: To describe the benefits and safety of using Carbon Dioxide Laser in multi-pulse modalities when performing labiaplasty and anatomical variants approach for functional and cosmetic indications.DESIGN: This is a prospective, descriptive case series study.SETTING: Private Practice Quirofano Calculaser Megacentro Pinares Pereira Colombia.POPULATION: One Hundred and twelve women seeking labia minora labiaplasty for functional and cosmetic reasons were enrolled in the study protocol from June 2013 to June 2016. Labia minora labioplasty and anatomical variants approach were performed with Carbon Dioxide laser Multi-pulse modalities DEKA M.EL.A Florence ItalyMAIN OUTCOME MEASURES: Good Cosmetic results, functional and sexuality improvementRESULTS: Dramatic changes in the VAS and VSQ were detected after the surgical procedure. All the participants reported a high degree of satisfaction, felt more confident with their partners during sexual encounters, and the procedure was well tolerated.CONCLUSION: Laser Carbon Dioxide Laser with a new pulse profile and shape seems to be a safe and precise surgical tool to perform this type of procedures, optimal biophysical and bio stimulative laser-tissue interactions allow delicate vulvar tissues to shorten downtime.

BACKGROUND: Postmenopausal women experience undesired symptoms that adversely affect their quality of life. In the recent years, a specific 12 - week fractional CO2 laser treatment has been introduced, with highly significant relief of symptoms. AIM: The aim of this paper is the identification of the early modifications of structural components of atrophic vaginal mucosa induced by laser irradiation, which is responsible for the restorative processes. MATERIAL AND METHODS: We investigated by microscopical, ultrastructural and biochemical methods the modifications of the structural components of postmenopausal atrophic vaginal mucosa tissues after 1 hour following a single fractional laser CO2 application. RESULTS: In one hour, the mucosal epithelium thickens, with the maturation of epithelial cells and desquamation at the epithelial surface. In the connective tissue, new papillae indenting the epithelium with newly formed vessels penetrating them, new thin fibrils of collagen III are also formed in a renewed turnover of components due to the increase of metalloproteinase - 2. Specific features of fibroblasts support stimulation of their activity responsible of the renewal of the extracellular matrix, with an increase of mechanical support as connective tissue and stimulation of growth and maturation to epithelium thanks to new vessels and related factors delivered. CONCLUSION: We found the activation of regenerative mechanisms expressed both in the connective tissue - with the formation of new vessels, new papillae, and new collagen - and in the epithelium with the associated thickening and desquamation of cells at the mucosal surface.

The authors show a brief overview of the vitiligo’s unconventional therapies. A part for well-documented effectiveness of L-phenylalanine, PGE2 and antioxidant agents in the treatment of vitiligo, for the other therapeutical approaches more investigations are needed.

BACKGROUND: Vitiligo is an acquired pigmentary cutaneous disease, characterised by the progressive loss of melanocytes, resulting in hypopigmented skin areas which progressively become amelanotic. Classically, vitiligo treatments are unsatisfactory and challenging. Despite the continuous introduction of new therapies, phototherapy is still the mainstay for vitiligo repigmentation.AIM: The aim of this multicenter observational retrospective study was to evaluate the efficacy and safety of the nb - UVB micro - phototherapy (BIOSKIN EVOLUTION®), used alone or in associations with an oral Janus kinase inhibitor (Tofacitinib citrate), in the treatment of stable or active forms of localised vitiligo.MATERIAL AND METHODS: Fifty eight patients had been treated with n-UVB micro-photootherapy (Group A); 9 patients had been treated with phototherapy plus Tofacitinb citrate (Group B).RESULTS: Among Group A, 42 patients (72%) obtained a re-pigmentation rate higher than 75%, with a medium value of 77%. 11 patients (19%) achieved a marked improvement of the clinical findings with a repigmentation rate between 50-75%; 4 patients (8%) showed a moderate response with a lesional repigmentation of 25-50%. Only one patient (1%) had a poor response to the phototherapeutic treatmentCONCLUSION: Nb - UVB micro-focused phototherapy is one of the most effective therapeutic options for vitiligo treatment. The association of micro-focused phototherapy to Tofacitinib citrate seems to provide better clinical results in term of repigmentation rate.

We present a 35-year-old male patient with Bureau-Barrière syndrome. Bureau-Barrière syndrome is an ulcero-mutilating acropathy almost invariably associated with excessive alcohol intake. It presents with a triad of trophic skin changes with recurrent ulcerations, bone lesions and nerve damage. The clinical presentation includes chronic painless plantar ulcerations with periulcerous hyperkeratosis, hyperhidrosis, livedoid skin colour, nail dystrophy, widening and infiltration of the toes and common interdigital mycoses. Other non-specific skin changes related to the alcohol consumption are commonly observed as well. The condition affects mainly middle-aged men suffering from alcoholism. Often a bilateral location at the lower limb of male alcoholics has been described, as in our patient. Successful treatment of the Bureau-Barrière syndrome requires an interdisciplinary approach. Cessation of alcohol intake and smoking is of paramount importance.

A 48 years old female patient had been suffering from the lesions presented for four years. They have started as small, pruritic patches which had been mechanically irritated and grew up in time. The patient had no associated comorbidities or allergies, and she was not under any medication. On physical examination, she presented one erythematous, exudative plaque, with dimensions of 2.5/4 cm, located on the proximal phalanx and interphalangeal articulation of the left thumb. All histopathological features were consistent with the diagnosis of lichen simplex chronicus. Some lesions of lichen simplex chronicus exhibit signs of pseudocarcinomatous, infundibular and sometimes eccrine ductal proliferation of keratinocytes. Although the pseudoinfiltrative aspect of the epithelial proliferation and its pronounced degree might mimic a well-differentiated lesion of squamous cell carcinoma, a lack of cellular atypia and atypical mitotic figures are features that do not support this diagnosis. On the other hand, long lasting lesions of lichen simplex chronicus may lead to alterations in the processes of keratinocyte proliferation and differentiation and eventually give rise to malignant transformation. The best treatment management is a psychodermatological approach, a combination of skin care with psychotherapy, in order to prevent relapses.

Basal cell carcinoma (BCC) is the most common human malignancy, accounting for the majority of all non-melanoma skin cancers (NMSC). In the past several decades the worldwide incidence of BCC has constantly been increasing. Even though it is a slow growing tumour that, left untreated, rarely metastasizes, it has a distinctive invasive growth pattern, posing a considerable risk for local invasion and destruction of underlying tissues, such as muscle, cartilage, bone or vital structures. Advanced BCCs include such locally invasive or metastatic tumours. Complete surgical excision is the standard therapy for most uncomplicated BCC cases with good prognosis and cure rates. Treatment of advanced forms of BCCs poses significant therapeutic challenges, most often requiring complicated surgery, radiotherapy, and/or targeted therapies directed towards the sonic hedgehog signalling pathway (SHH). We present two cases of large BCCs located on the scalp and posterior thorax, which underwent surgical excision with clear margins, followed by reconstruction of the defect after extensive undermining of the skin.

A 16 years old female patient, affected by atopic dermatitis and rhinoconjunctivitis allergica since childhood, requested a dermatologic consultation for lesions which had appeared after 3 months of local treatment with clobethasole propionate. The histological analysis confirmed the diagnosis of dyshidrotic eczema and the microbiological smears demonstrated a significant infection with Staphylococcus aureus. The risk of developing corticosteroids’ side-effects depends on the potency of the product, extended period of use and the volume of product applied. Clobetasol propionate is a group I- highly potent corticosteroid, which should be used for a maximum period of 2 weeks. Several authors have found that this agent has cumulative depot effect, persisting in the epidermis for 4 days after only one application. Taking together these observations, sustained by the clinical case presented above, we can conclude that the infectious risks associated with topical corticosteroid treatment must not be neglected, particularly since treated patients are fragile, and frequently have multiple well-known risk factors.

A 60-year-old male patient presented with complaints of persistent red to a brown-colored plaque on his scrotum, with duration of approximately three years. The patient had been treated with oral and topical antifungals for inguinal tinea for several months and after that with topical corticosteroids for eczema for several more months. None of the regimens achieved any therapeutic effect. The histopathological evaluation revealed the presence of atypical keratinocytes in all layers of the epidermis with the altered epidermal pattern, spread parabasal mitotic activity, without secondary satellites, multiple dyskeratotic cells and multinucleated cells. The diagnosis of an intraepithelial non-invasive squamous cell carcinoma, associated with koilocytic dysplasia and hyperplasia was made, meeting the criteria for Bowen disease. An elliptic surgical excision of the lesion was made, while the defect was closed with single stitches, with excellent therapeutic and aesthetic result. First described by John T. Bowen in 1912, Bowen disease (BD) represents a squamous cell carcinoma (SCC) in situ with the potential for significant lateral spread. Treatment options include the application of topical 5-flurorouracil cream – useful in non-hairy areas, imiquimod cream or destructive methods such as radiation, curettage, cryotherapy, laser ablation and photodynamic therapy, especially useful in nail bed involvement. Despite the early lesions, surgical excision is the preferred treatment option, regarding the potential malignant transformation risk.

We report a patient with a verrucous keratotic variant of melanoma visiting the policlinic of Medical Institute of Ministry of Interior (MVR-Sofia), Department of Dermatology and Dermatologic surgery, with a keratotic verrucous lesion, located on the right thigh, partially deeply pigmented at upper right quadrant. The lesion had appeared three years ago before her presentation in the policlinic, and it had gradually enlarged and become darker in the last twelve months. The surface of the lesion was covered with thick hyperkeratotic lobules. The histologic evaluation revealed verrucous melanoma with a tumour thickness of 3 mm and Clark Level IV and focal ulceration. The tumour was staged as stage IIB (T3bN0M0). Sentinel lymph node biopsy was planned. Verrucous-keratotic forms of malignant melanoma occur more commonly in women and favour the extremities, but may be found on any anatomic site. Seventy-one percent of this melanoma type are situated on the upper and lower extremities. Although two-thirds of these neoplasms can be can be histologically graded according to the classification of Clark, one-third of these melanomas with marked verrucous hyperplasia and hyperkeratosis of the epidermis do not fit into his classification. Histological classification of patients with a verrucous keratotic type of melanoma may sometimes be extremely difficult. The marked papilliferous architecture of these lesions made an assessment of Breslow depth difficult. The presented case highlights the clinical existence and features of such benign-looking melanomas. It is therefore important for surgical pathologists to recognise this unusual variant of malignant melanoma, as it may be confused both clinically and pathologically with benign lesions.

We report the case of a 42 years old male patient suffering from skin changes , which appeared in the last 7-8 years. Two biopsies were performed during the evolution of the lesion. Both showed similar findings that consisted in a busy dermis with interstitial, superficial and deep infiltrates of lymphocytes and histiocytes dispersed among collagen bundles, with variable numbers of neutrophils scattered throughout. Some histiocytes were clustered in poorly formed granuloma that included rare giant cells, with discrete Palisades and piecemeal collagen degeneration, but without mucin deposition or frank necrobiosis of collagen. The clinical and histologic findings were supportive for interstitial granulomatous dermatitis. Interstitial granulomatous dermatitis (IGD) is a poorly understood entity that was regarded by many as belonging to the same spectrum of disease or even synonym with palisaded and neutrophilic granulomatous dermatitis (PNGD). Although IGD and PNGD were usually related to connective tissue disease, mostly rheumatoid arthritis, some patients with typical histologic findings of IGD never develop autoimmune disorders, but they have different underlying conditions, such as metabolic diseases, lymphoproliferative disorders or other malignant tumours. These observations indicate that IGD and PNGD are different disorders with similar manifestations.

A 61-year-old woman, with a lifelong history of a giant congenital melanocytic nevus in the occipital region with secondary development of giant melanoma is presented. Surgical excision was performed, and the histopathological evaluation confirmed the diagnosis of Giant Malignant Melanoma (GMM) with a maximum tumour thickness of 16 mm. Nowadays, there is tremendous uncertainty regarding how giant congenital melanocytic nevi (GCMN) should be treated. The standard approach to patients with late onset giant congenital melanocytic nevi (GCMN is based on two main considerations: (1) obtain an acceptable cosmetic results with the purpose to decrease the psychosocial inconvenience to each patient, and (2) to attempt to minimise the risk of development of malignant transformation. Unfortunately complete surgical removal of the GCMN is usually difficult and very often impossible without subsequent functional or cosmetic mutilations.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequently encountered neoplasm worldwide. While nodular BCC is the most frequent clinical subtype, other forms of BCC, such as superficial, cystic, morpheiform, infiltrative, and pigmented may also be encountered.CASE PRESENTATION: We present the case of a 67-year-old male with a relatively well-defined infiltrative, pigmented plaque with multiple colours and peripheral growth situated in the right axillary region. The histopathologic examination performed after complete surgical excision of the tumour revealed a complex pigmented BCC with macronodular, fibroepithelioma-like, cystic, focally infiltrative and basosquamous features.CONCLUSION: Uncommon locations of BCCs in sun-protected areas such as the axillary region require a higher degree of suspicion for diagnosis. The complex histology of the presented case, including subtypes with differing biologic attributes, emphasises the importance of histopathological examination in the diagnosis and therapeutic management of BCC.

The main objective in dermatologic surgery is complete excision of the tumour while achieving the best possible functional and cosmetic outcome. Also we must take into account age, sex, and tumour size and site. We should also consider the patient's expectations, the preservation of the different cosmetic units, and the final cosmetic outcome. Various reconstructive methods ranging from secondary healing to free flap applications are usedfor the reconstruction of perinasal or facial defects caused by trauma or tumour surgery. Herein, we describe the nasal infraorbital island skin flap for the reconstruction in a patient with basal cell carcinoma. No complications were observed in operation field. The infraorbital island skin flap which we describe for the perinasal area reconstruction is a safe, easily performed and versatile flap. The multidimensional use of this flap together with a relatively easy reconstruction plan and surgical procedure would be effective in flap choice.

The plasma membrane of cardiac myocytes presents complex invaginations known as the transverse-axial tubular system (TATS). Despite TATS's crucial role in excitation-contraction coupling and morphological alterations found in pathological settings, TATS's electrical activity has never been directly investigated in remodeled tubular networks. Here we develop an ultrafast random access multiphoton microscope that, in combination with a customly synthesized voltage-sensitive dye, is used to simultaneously measure action potentials (APs) at multiple sites within the sarcolemma with submillisecond temporal and submicrometer spatial resolution in real time. We find that the tight electrical coupling between different sarcolemmal domains is guaranteed only within an intact tubular system. In fact, acute detachment by osmotic shock of most tubules from the surface sarcolemma prevents AP propagation not only in the disconnected tubules, but also in some of the tubules that remain connected with the surface. This indicates that a structural disorganization of the tubular system worsens the electrical coupling between the TATS and the surface. The pathological implications of this finding are investigated in failing hearts. We find that AP propagation into the pathologically remodeled TATS frequently fails and may be followed by local spontaneous electrical activity. Our findings provide insight on the relationship between abnormal TATS and asynchronous calcium release, a major determinant of cardiac contractile dysfunction and arrhythmias.

A 63-year-old Caucasian female patient presented with redness of the both foot and lower legs, as well as edema of the left lower leg, accompanied by subjective complaints of burning. Fever was not reported. Well-circumscribed oval shaped tumor formation was revealed also on the abdominal wall, with hyperpigmented and depigmented areas on its ulcerated surface, measuring approximately 10/10cm in diameter, with soft-elastic texture on palpation. The lesion occurred in 2011, according to the patient’s history. No subjective complaints were reported in association. The performed ultrasonography revealed intestinal loops in the hernial sac, without incarceration. The diagnosis of ventral abdominal hernia without mechanical ileus was made. The patient was referred for planned surgical procedure, because of her refusal on this stage.The clinical manifestation of the tumor formation on the abdominal wall, required wide spectrum of differential diagnosis, including aneurysm of the abdominal aorta, abdominal tumor, subcutaneous tumor or metastasis or hernia. In the presented cases, the abdominal wall mass was a sporadic clinical finding in the framework of the total-body skin examination in patient with erysipelas. The lack of subjective symptoms, as well as the reported history for hysterectomy and previously abscessus were not enough indicative symptoms for the correct diagnosis. The diagnosis of non-complicated hernia was made via ultrasonography, while the clinical differentiation between hernia and other life-threatening conditions as aneurysms or tumor was not possible.

We present a 68-year-old patient with multiple primary infiltrative BCCs in the scalp area, initially treated 14 years ago with superficial contact X-ray therapy, end dose 60 greys, followed by electrocautery (x2) several years later. He presented in the dermatologic policlinic for diagnosis and therapy of two additional, newly-formed pigmented lesions, and because of an uncomfortable, itchy, burning sensation in the area where lesions had been treated years before. Screening cranial computer-tomography (CT) examination revealed two deformities in the form of tumor-mediated osteolysis, affecting the diploe of the tabula externa on the left parietal and parasagittal areas. Complete excision with removal of periosteum and partial removal of the tabula externa was planned with neurosurgeons at a later stage. BCC is one of the most common malignant skin tumours of the head and neck region (about 90% of cases) and is characterised by a significant potential for local infiltration and destructive growth. Recurrent, invasive BCC of the scalp and calvarium is a difficult problem for which universally accepted treatment protocols had not been established. The primary treatment of aggressive BCCs is surgical, with a thorough examination of excision margins to ensure complete resection. Procedural-based options include standard excision, curettage, curettage with electrodessication, and Mohs micrographic surgery (MMS), with MMS being the gold standard for the definitive treatment of BCC. Improper removal or electrocautery (as in our case) of the several aggressive forms of BCC seems to be a particular problem, and not only for dermatologic surgeons. The risk of subsequent invasion and destruction of the cranium, underlying dura, and cranial nerves by basal cell carcinoma (BCC) is extremely low, with an estimated incidence of 0.03%, but is a potential complication over time. Computed tomography is the modality of choice for detecting tumour invasion into bone, which commonly appears as irregular demineralization or osteolysis.

A 73-year-old male patient was admitted with symptoms of decompensated cardiac and pulmonary insufficiency with long-lasting history. A tumor-like formation was observed within the clinical examination, covering the whole skin of the nose, paranasal region of the left part of the face, as well as the upper and lower left eyelids. The lesion was with yellow to brownish surface and dark-reddish to violet discolored peripheral area, composed of nodular formations, smooth central surface and firm texture on palpation. The histopathological examination verified the diagnosis of hemangioma, which had been congenital, regarding the patient’s history, treated surgically about 50 years ago, with signs of recurrence. The presented patient had been treated surgically at the age of 20, without medical evidence of the type of the performed excision. The recurrence occurs almost 50 years later, at the age of 78. To the best of our knowledge, this is the first reported recurrence of infantile hemangioma, treated surgically almost 50 years ago.

We combined the advantage of an ultrafast random access microscope with novel labelling technologies to study the intra- and inter-cellular action potential propagation in neurons and cardiac myocytes with sub-millisecond time resolution. The random accesses microscopy was used in combination with a new fluorinated voltage sensitive dye with improved photostability to record membrane potential from multiple Purkinje cells with near simultaneous sampling. The RAMP system rapidly scanned between lines drawn in the membranes of neurons to perform multiplex measurements of the TPF signal. This recording was achieved by rapidly positioning the laser excitation with the AOD to sample a patch of membrane from each cell in

Understanding brain structure and function, and the complex relationships between them, is one of the grand challenges of contemporary sciences. Thanks to their flexibility, optical techniques could be the key to explore this complex network. In this manuscript, we briefly review recent advancements in optical methods applied to three main issues: anatomy, plasticity and functionality. We describe novel implementations of light-sheet microscopy to resolve neuronal anatomy in whole fixed brains with cellular resolution. Moving to living samples, we show how real-time dynamics of brain rewiring can be visualized through two-photon microscopy with the spatial resolution of single synaptic contacts. The plasticity of the injured brain can also be dissected through cutting-edge optical methods that specifically ablate single neuronal processes. Finally, we report how nonlinear microscopy in combination with novel voltage sensitive dyes allow optical registrations of action potential across a population of neurons opening promising prospective in understanding brain functionality. The knowledge acquired from these complementary optical methods may provide a deeper comprehension of the brain and of its unique features.

Optical recording of membrane potential permits spatially resolved measurement of electrical activity in subcellular regions of single cells, which would be inaccessible to electrodes, and imaging of spatiotemporal patterns of action potential propagation in excitable tissues, such as the brain or heart. However, the available voltage-sensitive dyes (VSDs) are not always spectrally compatible with newly available optical technologies for sensing or manipulating the physiological state of a system. Here, we describe a series of 19 fluorinated VSDs based on the hemicyanine class of chromophores. Strategic placement of the fluorine atoms on the chromophores can result in either blue or red shifts in the absorbance and emission spectra. The range of one-photon excitation wavelengths afforded by these new VSDs spans 440–670 nm; the two-photon excitation range is 900–1,340 nm. The emission of each VSD is shifted by at least 100 nm to the red of its one-photon excitation spectrum. The set of VSDs, thus, affords an extended toolkit for optical recording to match a broad range of experimental requirements. We show the sensitivity to voltage and the photostability of the new VSDs in a series of experimental preparations ranging in scale from single dendritic spines to whole heart. Among the advances shown in these applications are simultaneous recording of voltage and calcium in single dendritic spines and optical electrophysiology recordings using two-photon excitation above 1,100 nm.

In combination with fluorescent protein (XFP) expression techniques, two-photon microscopy has become an indispensable tool to image cortical plasticity in living mice. In parallel to its application in imaging, multi-photon absorption has also been used as a tool for the dissection of single neurites with submicrometric precision without causing any visible collateral damage to the surrounding neuronal structures. In this work, multi-photon nanosurgery is applied to dissect single climbing fibers expressing GFP in the cerebellar cortex. The morphological consequences are then characterized with time lapse 3-dimensional two-photon imaging over a period of minutes to days after the procedure. Preliminary investigations show that the laser induced fiber dissection recalls a regenerative process in the fiber itself over a period of days. These results show the possibility of this innovative technique to investigate regenerative processes in adult brain. In parallel with imaging and manipulation technique, non-linear microscopy offers the opportunity to optically record electrical activity in intact neuronal networks. In this work, we combined the advantages of second-harmonic generation (SHG) with a random access (RA) excitation scheme to realize a new microscope (RASH) capable of optically recording fast membrane potential events occurring in a wide-field of view. The RASH microscope, in combination with bulk loading of tissue with FM4-64 dye, was used to simultaneously record electrical activity from clusters of Purkinje cells in acute cerebellar slices. Complex spikes, both synchronous and asynchronous, were optically recorded simultaneously across a given population of neurons. Spontaneous electrical activity was also monitored simultaneously in pairs of neurons, where action potentials were recorded without averaging across trials. These results show the strength of this technique in describing the temporal dynamics of neuronal assemblies, opening promising perspectives in understanding the computations of neuronal networks.