Clinical Applications of System Regulation Medicine.

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.

A Black Hole at the Center of Earth Plays the Role of the Biggest System of Telecommunication for Connecting DNAs, Dark DNAs and Molecules of Water on 4+N- Dimensional Manifold.

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.

Recovery of Brain in Chick Embryos by Growing Second Heart and Brain.

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.

In Ovo Sexing of Chicken Eggs by Virus Spectroscopy.

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.

DNA Waves and Their Applications in Biology.

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.

Formation of Neural Circuits in an Expanded Version of Darwin's Theory: Effects of DNAs in Extra Dimensions and within the Earth's Core on Neural Networks.

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.

A Mathematical Model for the Signal of Death and Emergence of Mind Out of Brain in Izhikevich Neuron Model.

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.

Apitherapy as a New Approach in Treatment of Palmoplantar Psoriasis.

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 psoriasis. CONCLUSION: 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.

Is There a Place for Local Natural Treatment of Psoriasis?

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.

In Vitro Evaluation of the Biosafety of Hyaluronic Acid PEG Cross-Linked with Micromolecules of Calcium Hydroxyapatite in Low Concentration.

OBJECTIVE: Neauvia Stimulate is biocompatible, injectable hyaluronic acid (HA) filler (26 mg/ml) PEG cross-linked 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.

Early Regenerative Modifications of Human Postmenopausal Atrophic Vaginal Mucosa Following Fractional CO2 Laser Treatment.

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.

In Vitro Evaluation of the Sensitivity of a Hyaluronic Acid PEG Cross-Linked to Bovine Testes Hyaluronidase.

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.

Carbon Dioxide with a New Pulse Profile and Shape: A Perfect Tool to Perform Labiaplasty for Functional and Cosmetic Purpose.

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 Italy. MAIN OUTCOME MEASURES: Good Cosmetic results, functional and sexuality improvement. RESULTS: 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.

Intralesional Diode Laser 1064 nm for the Treatment of Hidradenitis Suppurativa: A Report of Twenty Patients.

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.

Automatic Artificial Hair Implant: Safety and Efficacy in Androgenetic Alopecia. A Prospective Study with a Highly Biocompatible Fiber.

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.

Successful Treatment with UVA 1 Laser of Non - Responder Vitiligo Patients.

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.

Micro - Focused Phototherapy Associated To Janus Kinase Inhibitor: A Promising Valid Therapeutic Option for Patients with Localized Vitiligo.

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 treatment. CONCLUSION: 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.

An Innovative Therapeutic Protocol for Vitiligo: Experience with the Use of Fraxel Herbium Laser, Topical Latanoprost and Successive Irradiation with UVA - 1 Laser.

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.

Neglected Under Lip Cancer.

The lip represents an anatomical area of the interface between the skin and oral mucosa. It is, therefore, not entirely surprising that SCC of the lip exhibits mixed features between cutaneous and oral mucosal SCC, namely regarding risk factors and biological behaviour. The main risk factors for lip SCC include ultraviolet radiation exposure, low phototype, tobacco and alcohol use, and immunosuppression. Lip SCC usually presents clinically as a nodule or a tumour with a keratotic surface that commonly ulcerates. There is often a background of actinic cheilitis. The particularly exuberant presentation of our case can most probably be explained by the long evolution of a tumour before the patient reached medical attention. Patients with regional lymph node metastasis are usually offered regional lymph node dissection (usually of the neck). Radiotherapy and/or chemotherapy may be used in advanced cases, particularly in unresectable tumours, tumours with high-risk features and metastatic disease. The large size of a tumour in our case, most probably due to its long evolution, highlights the importance of timely diagnosis to avoid such extreme presentations and the consequent need for more aggressive treatment.

Sweet's Syndrome (SS) in the Course of Acute Myeloid Leukaemia (AML).

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.