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The main surgical treatment for melanoma consists in wide surgical excision of the primary lesion and the sentinel node but in recent times management of melanoma is rapidly evolving with the introduction of new systemic therapies, like BRAF inhibitors, MEK inhibitors and antibodies anti-PD-1 that show good results in controlling even advanced stages of the disease. This review aims to present data for the optimal surgical management of patients with malignant melanoma., (Copyright: © 2019 Jacopo Scala, Aleksandra Vojvodic, Petar Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica Peric-Hajzler, Dusica Matovic, Sanja Dimitrijevic, Jovana Vojvodic, Goran Sijan, Nenad Stepic, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Massimo Fioranelli, Torello Lotti.)

The P.N.E.I. (Psycho-Neuro-Endocrine-Immunology) approach is represented by the interdisciplinary concept of bidirectional cross-talk between the psycho-neuro-endocrine and immune systems, which can influence the immune response. The well-known Gut-Brain Axis and the Gut-Skin Axis can be merged in a bigger network- the Gut-Brain-Skin Axis, with complex regulation by cytokines, neuro-peptides, neuro-hormones and another messenger (signalling) molecules and maybe the most important modulator of the Gut-Brain-Skin Axis/ the gut microbiota. The role of gut bacterial homeostasis is very important, and the homeostatic imbalance of the immune response may be a relevant etiologic/pathophysiologic factor for extra-intestinal and intestinal inflammatory, allergic and autoimmune diseases. The Low Dose Cytokines Medicine (LDM) is an innovative therapeutic approach. It is based on the most advanced knowledge in molecular biology and low dose pharmacology with the primary outcome. The SKA (Sequential Kinetic Activation) technology, codified and standardised by GUNA S.p.a. -Italy- makes the low doses of signalling molecules able to be active even below the minimum dose classically considered as effective and the significative efficacy of orally administered low-dose signalling molecules is the most representative aspect of LDM. The Physiologic Nutraceuticals and the Low Dose Medicine are two of the most promising approaches for the treatment of skin diseases based on the rebalance of the immune response and the recovery of gut dysbiosis., (Copyright: © 2019 Aleksandra Vojvodic, Zorica Peric-Hajzler, Dusica Matovic, Petar Vojvodic, Tatjana Vlaskovic-Jovicevic, Goran Sijan, Sanja Dimitrijevic, Nenad Stepic, Uwe Wollina, Badr Abdulwahab E. Badr, Ashraf Badawi, Mohamad Goldust, Michael Tirant, Van Thuong Nguyen, Massimo Fioranelli, Torello Lotti.)

It is determined that 30% of patients with depression are resistant to antidepressant medication. The increased concentration of inflammation factors, such as C-reactive protein, and pro-inflammatory cytokines, have been detected in serum in these patients. It is necessary to establish new therapeutic possibilities and protocols that are created to overcome the difficulties caused by increased concentration of inflammatory biomarkers in depressive patients. The Selective Serotonin Reuptake Inhibitors (SSRIs) are considered to be the most powerful antidepressants, increasing the level of serotonin in endogenous depression, as well as in that caused by immunological mechanisms. It is believed that agents that influence cytokines, immunological signal pathways and cytokine syntheses, like the inhibitors of cyclooxygenase enzyme and other non-steroidal anti-inflammatory drugs (NSAIDs), are very important in the potential treatment of residual symptoms of depression. Treatment with cytokine antagonists is one of the potential adjuvant therapies, along with antidepressants. Signal pathways blockers, such as the inhibitors of cyclooxygenase and other NSAIDs, are in the phase of research, in terms of their antidepressant effects. Also, it has been shown that the inhibition of indolamin-2,3 deoxygenase (IDO) and kynurenine (KYN) signal pathways in the synthesis of neurotransmitters, by application of IDO antagonists, are leading to suppression of pro-inflammatory cytokine effects. Antidepressants may have anti-inflammatory effects, depending on dose and type, and they achieve this effect through the decrease of pro-inflammatory cytokine production and increase of anti-inflammatory cytokines. Also, antidepressants modulate the humoral and cellular immune system. This work aims to summarise certain neurobiological and neuroimmunological specificities that have been observed in patients with depression, antidepressants and immunomodulation agents. The understanding of complex and heterogenic pathophysiology of depression through the prism of the altered immune system, is of major importance, in terms of better optimisation of pharmacotherapy, and options for a personalised approach in depressive disorder treatment., (Copyright: © 2019 Jovana Vojvodic, Goran Mihajlovic, Petar Vojvodic, Dusan Radomirovic, Aleksandra Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica Peric-Hajzler, Dusica Matovic, Sanja Dimitrijevic, Goran Sijan, Maria Grazia Roccia, Massimo Fioranelli, Torello Lotti.)

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. In this research, summing over these considerations, a new technique for sexing of chicken eggs by virus spectroscopy through the shell membrane is proposed. It is shown that viruses outside the shell of egg can communicate with materials inside it and determine the gender of chick embryo and it's evolutions., (Copyright: © 2019 Massimo Fioranelli, Alireza Sepehri, Maria Grazia Roccia, Chiara Rossi, Petar Vojvodic, Jacopo Lotti, Victoria Barygina, Aleksandra Vojvodic, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Sanja Dimitrijevic, Goran Sijan, Zorica Peric-Hajzler, Dusica Matovic, Tatjana Vlaskovic-Jovicevic, Torello Lotti.)

Aim: In this research, we show that DNA waves have many applications in biology. DNA is formed by the joining of quantum particles like electrons and charged atoms. DNA has different motions during transcription, translation, and replication, in which the charged particles move, accelerate, and emit waves. Thus, DNA could emit quantum waves., Methods: Two methods are proposed to observe the effect of DNA waves. The first proposed method measures DNA waves emitted by bacteria suspended in the milk. The vessel of milk is placed in the interior of an inductor. One side of the vessel is connected to a generator and another side to a scope. By sending a current to the inductor, an input electromagnetic field is produced. Bacteria interact with the input field, change it and produce new output signals. Using the scope, the output signals are observed and compared with the input signals. The number of DNA waves produced also depends on temperature., Results: At lower temperatures, bacterial replication is less, and fewer DNA waves are produced. Conversely, more bacteria are generated at higher temperatures, and more DNA waves are produced. The second proposed method acquires and images of DNA signals of chick embryos. In this method, a circuit is constructed that consists of a graphene or metal tube, generator, inductor, scope, DNA in the interior of eggs and DNA exterior to the eggs. Magnetic waves pass the interior and exterior DNA as well as the graphene. The DNA is excited and the exciting interior/exterior DNA exchanges waves. Some of these waves interact with electrons in the graphene tube, and a current is generated. Properties of the chick embryo DNA can be explored by analysing changes in the waves that emerge from the eggs., Conclusion: It is concluded that DNA waves could be used extensively in imaging and provide for us the exact information about evolutions of DNAs interior of biological systems., (Copyright: © 2019 Massimo Fioranelli, Alireza Sepehri, Maria Grazia Roccia, Chiara Rossi, Jacopo Lotti, Petar Vojvodic, Victoria Barygina, Aleksandra Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica Peric-Hajzler, Dusica Matovic, Jovana Vojvodic, Sanja Dimitrijevic, Goran Sijan, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Torello Lotti.)

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., (Copyright: © 2019 Massimo Fioranelli, Alireza Sepehri, Maria Grazia Roccia, Chiara Rossi, Jacopo Lotti, Victoria Barygina, Petar Vojvodic, Aleksandra Vojvodic, Tatjana Vlaskovic-Jovicevic, Jovana Vojvodic, Sanja Dimitrijevic, Zorica Peric-Hajzler, Dusica Matovic, Goran Sijan, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Torello Lotti.)

Subcutaneous adipose tissue was defined as the "perfect filler" as is soft and malleable and is usually enough present in the body for correcting volume defects and small remodelling purposes. The first attempts to implant autologous adipose tissue dates back to the end of the twentieth century, and with the refinement of harvesting, processing and replanting techniques today a uniform and predictable amount of survival rate were achieved. Those improvements have led to wider use of autologous fat grafts in many medical specialities not only in aesthetic or reconstructive treatments., (Copyright: © 2019 Jacopo Scala, Aleksandra Vojvodic, Petar Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica Peric-Hajzler, Dusica Matovic, Sanja Dimitrijevic, Jovana Vojvodic, Goran Sijan, Nenad Stepic, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Massimo Fioranelli, Torello Lotti.)

Insomnia means difficulty in falling asleep and/or stays asleep. Insomnia commonly leads to daytime sleepiness, lethargy, and a general feeling of being unwell. The most common treatment of insomnia includes GABAA receptor positive allosteric modulators or Melatonin agonists. Our study aimed to evaluate the efficacy of Magnesium- melatonin-vitamin B complex supplement in the treatment of insomnia. The study included 60 patients diagnosed with insomnia. The patients were randomly divided into study group (N = 30), and control group (N = 30), and study group was treated with Magnesium-melatonin-vitamin B complex (one dose contains 175 mg liposomal magnesium oxide, 10 mg Vit B6, 16 μg vit B12, melatonin 1 mg, Extrafolate-S 600 μg) once a day 1 hour before sleep, during the 3 months. The severity of insomnia symptoms was measured by self-reported Athens insomnia scale (AIS), with a cut-off score by Soldatos (AIS score ≥ 6). Mean AIS score at zero points was 14.93 ± 3.778 in the study group and 14.37 ± 4.081 in the control group (p = 0.476), indicating the compatibility of the groups, and both scores correspond to mild to moderate insomnia. Mean AIS score after 3 months of the Magnesium- melatonin- vitamin B complex supplementation was 10.50 ± 4.21 corresponding to mild insomnia, while median AIS score in the control group was 15.13 ± 3.76 which is referred to moderate insomnia, and difference among groups was significant (p = 0.000). Our founding's indicating that 3 months of the Magnesium- melatonin-vitamin B complex supplementation has a beneficial effect in the treatment of insomnia regardless of cause., (Copyright: © 2019 Gorica Djokic, Petar Vojvodić, Davor Korcok, Anita Agic, Anica Rankovic, Vladan Djordjevic, Aleksandra Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica Peric-Hajzler, Dusica Matovic, Jovana Vojvodic, Goran Sijan, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Massimo Fioranelli, Torello Lotti.)

Botulinum toxin (BTX) is a neurotoxin derived from the Clostridium botulinum bacterium that inhibits the release of acetylcholine at the neuromuscular junction level whose effects has been used for many years to treat a variety of muscular/neuromuscular conditions and more recently also for cosmetic use. BTX has experimented in some dermatological conditions, which include Rosacea and facial flushing treatment with good results. The complex mechanism underlying those results is not completely understood but was proposed a release inhibition of acetylcholine from peripheral autonomic nerves of the cutaneous vasodilatory system combined with the blockade substance P and calcitonin gene-related peptide (CGRP) thus modulating blood vessel dilatation. We analysed the published data on BTX off label applications rosacea and flushing retrieved from PubMed., (Copyright: © 2019 Jacopo Scala, Aleksandra Vojvodic, Petar Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica Peric-Hajzler, Dusica Matovic, Sanja Dimitrijevic, Jovana Vojvodic, Goran Sijan, Nenad Stepic, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Massimo Fioranelli, Torello Lotti.)

There are numerous cases reports and studies confirming the enhanced incidence of melanoma among patients with mastocytosis, especially with systemic mastocytosis. These two diseases are arising from two different types of cells; melanoma arises from neural crest cells and mastocytosis from hematopoietic stem cells. But there are a lot of similarities between the two diseases. The most important and significant is the dependence of the growth factor receptor c-KIT and c-KIT ligand (stem cell factor) for their growth and development. Also, expression of the STAT3 (signal transducer and activator of transcription 3) and transcription factors MITF (microphthalmia-associated transcription factor) make the connection between melanoma and mastocytosis., (Copyright: © 2019 Aleksandra Vojvodic, Tatjana Vlaskovic Jovicevic, Petar Vojvodic, Jovana Vojvodic, Mohamad Goldust, Zorica Peric Hajzler, Dusica Matovic, Goran Sijan, Nenad Stepic, Uwe Wollina, Massimo Fioranelli, Michael Tirant, Van Thuong Nguyen, Torello Lotti.)

Incidence of melanoma is increasing every year. A few years ago, we could not speak about long term survivors with melanoma. Chemotherapy did not give a good effect in the past. Metastasis occurred very rapidly, and the progression of melanoma was very fast. But now, with new forms of therapy, especially immunotherapy and target therapy, for the first time, we have long-time survivors. For the prognosis of melanoma, the most important is the stage in which melanoma is detected. For all dermatologists, it is very important to be aware of the psychological impact of melanoma on patients. Dermatologists should recognise psychological disorders. Several different scales can be used for the detection of depression and anxiety - some of them are completed by researchers, some of them are completed by patients, and also, we have combined scales. The need for adequate social and family support as well as psychological help to achieve better coping with illness is necessary. Learning techniques to overcome fear and stress would help in better functioning of all affected, regardless of the stage of the disease. The most severe cases of anxiety and depression, in addition to psychotherapeutic interventions, should also be considered medication therapy., (Copyright: © 2019 Aleksandra Vojvodic, Tatjana Vlaskovic-Jovicevic, Petar Vojvodic, Jovana Vojvodic, Mohamad Goldust, Zorica Peric-Hajzler, Dusica Matovic, Goran Sijan, Nenad Stepic, Van Thuong Nguyen, Michael Tirant, Uwe Wollina, Torello Lotti, Massimo Fioranelli.)

Understanding the mechanisms of cancer immune-tolerance is one of the most important challenges. Several studies have demonstrated the potential anticarcinogenic effects of beta-blockers, in patients with prostate cancer, breast cancer, and melanoma. At the other side variety of dermatoses may be caused or aggravated by β-blockers-psoriasis, lichen planus-like drug eruptions (LDE), acrocyanosis, alopecia etc. Beta-blockers have been shown to improve the prognosis of melanoma patients significantly. Propranolol inhibits melanoma by downregulating the tumour angiogenesis but also tumour cell proliferation, invasiveness and local immune suppression. Studies showed that only β3-but, not β2-adrenoceptors, were up-regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub-populations including Treg, MDSC, and NK. They increased NK and CD8 number and cytotoxicity. Catecholamines may retard melanoma progression and that β-blockers may have unrecognised potential as a therapeutic intervention for melanoma, in the prevention of the growth of melanoma in all stages and as adjuvant therapy with other targeted and immune therapies for melanoma., (Copyright: © 2019 Aleksandra Vojvodic, Petar Vojvodic, Tatjana Vlaskovic-Jovicevic, Goran Sijan, Sanja Dimitrijevic, Zorica Peric-Hajzler, Dusica Matovic, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Massimo Fioranelli, Torello Lotti.)

Botulinum toxin (BTX) is a neurotoxin protein derived from the Clostridium botulinum bacterium that inhibits the release of acetylcholine at the neuromuscular junction level whose effects has been used for many years to treat a variety of muscular/neuromuscular conditions and more recently also for cosmetic use. BTX has experimented in some dermatological conditions which include scar prevention and treatment with good results The complex mechanism underlying those results is not completely understood but several mechanisms were proposed release inhibition of different substances like (TGF)-β, substance P, calcitonin gene-related peptide (CGRP) and glutamate thus modulating cutaneous inflammation and wound healing. We analysed the published data on BTX off label applications on scars and keloids retrieved from PubMed., (Copyright: © 2019 Jacopo Scala, Aleksandra Vojvodic, Petar Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica Peric-Hajzler, Dusica Matovic, Sanja Dimitrijevic, Jovana Vojvodic, Goran Sijan, Nenad Stepic, Uwe Wollina, Michael Tirant, Nguyen Van Thuong, Massimo Fioranelli, Torello Lotti.)