Search results for: endoscopic vacuum therapy

Authors: Shashank Patidar, Sumit Kumar, Atul Srivastava, Suneet Singh

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Present work is concerned with the numerical investigation of thermal response of biological tissues during laser-based photo-thermal therapy for destroying cancerous/abnormal cells with minimal damage to the surrounding normal cells. Light propagation through the biological sample is mathematically modelled by transient radiative transfer equation. In the present work, application of the Lattice Boltzmann Method is extended to analyze transport of short-pulse radiation in a participating medium.In order to determine the two-dimensional temperature distribution inside the tissue medium, the RTE has been coupled with Penne’s bio-heat transfer equation based on Fourier’s law by several researchers in last few years.

Keywords: lattice Boltzmann method, transient radiation transfer equation, dual phase lag model

Procedia PDF Downloads 352

Authors: Zhaoyang Liu

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It has been highly desired to develop a high-performance membrane for separating oil/water emulsions with the combined features of high water flux, high oil separation efficiency, and high mechanical stability. Here, we demonstrated a design for high-performance membranes constructed with ultra-long titanate nanofibers (over 30 µm in length)/cellulose microfibers. An integrated network membrane was achieved with these ultra-long nano/microfibers, contrast to the non-integrated membrane constructed with carbon nanotubes (5 µm in length)/cellulose microfibers. The morphological properties of the prepared membranes were characterized by A FEI Quanta 400 (Hillsboro, OR, United States) environmental scanning electron microscope (ESEM). The hydrophilicity, underwater oleophobicity and oil adhesion property of the membranes were examined using an advanced goniometer (Rame-hart model 500, Succasunna, NJ, USA). More specifically, the hydrophilicity of membranes was investigated by analyzing the spreading process of water into membranes. A filtration device (Nalgene 300-4050, Rochester, NY, USA) with an effective membrane area of 11.3 cm² was used for evaluating the separation properties of the fabricated membranes. The prepared oil-in-water emulsions were poured into the filtration device. The separation process was driven under vacuum with a constant pressure of 5 kPa. The filtrate was collected, and the oil content in water was detected by a Shimadzu total organic carbon (TOC) analyzer (Nakagyo-ku, Kyoto, Japan) to examine the separation efficiency. Water flux (J) of the membrane was calculated by measuring the time needed to collect some volume of permeate. This network membrane demonstrated good mechanical flexibility and robustness, which are critical for practical applications. This network membrane also showed high separation efficiency (99.9%) for oil/water emulsions with oil droplet size down to 3 µm, and meanwhile, has high water permeation flux (6.8 × 10³ L m⁻² h⁻¹ bar⁻¹) at low operation pressure. The high water flux is attributed to the interconnected scaffold-like structure throughout the whole membrane, while the high oil separation efficiency is attributed to the nanofiber-made nanoporous selective layer. Moreover, the economic materials and low-cost fabrication process of this membrane indicate its great potential for large-scale industrial applications.

Keywords: membrane, inorganic nanofibers, oil/water separation, emulsions

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Authors: Chamseddine Barki, Salam Labidi, Hanen Boussi Rahmouni

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In this article, we present the principle and suitable methodology for the design of a medical ontology that highlights the radiological and dosimetric knowledge, applied in diagnostic radiology and radiation-therapy. Our ontology, which we named «Onto.Rap», is the subject of radiation protection in medical and radiology centers by providing a standardized regulatory oversight. Thanks to its added values of knowledge-sharing, reuse and the ease of maintenance, this ontology tends to solve many problems. Of which we name the confusion between radiological procedures a practitioner might face while performing a patient radiological exam. Adding to it, the difficulties they might have in interpreting applicable patient radioprotection standards. Here, the ontology, thanks to its concepts simplification and expressiveness capabilities, can ensure an efficient classification of radiological procedures. It also provides an explicit representation of the relations between the different components of the studied concept. In fact, an ontology based-radioprotection expert system, when used in radiological center, could implement systematic radioprotection best practices during patient exam and a regulatory compliance service auditing afterwards.

Keywords: knowledge, ontology, radiation protection, radiology

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Authors: Shweta Shriwas, Sumeet Dwivedi

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Knowledge of use of traditional medicine is as old as human civilization in almost every system of medicine. Traditional practitioner viz., vaidhayas, ojha, hakim have their own herbal therapy in the treatment of infertility among women’s. Infertility is very common in developed and developing countries due to busy life style of women’s. The present study was initiated with an aim to identify medicinal plants resources from traditional practitioners of Malwa region of Madhya Pradesh to treat infertility. An ethnomedicinal study of Malwa region viz., Indore, Dewas, Ratlam, Ujjain, Dhar, Mandsour and Neemuch of Madhya Pradesh, India comprising fifty-seven study site was conducted during Jan-217 to June-2017. During the course of present investigation, the traditional use of medicinal plants for infertility in women was revealed by traditional practitioner. The botanical name, family, local name, part used, habit along with mode of their administration and dose duration were enumerated.

Keywords: herbal medicine, infertility, traditional, Malwa, Madhya Pradesh

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Authors: Hassan Qandil

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Using a statistical algorithm incorporated in MATLAB, four types of non-imaging Fresnel lenses are designed; spot-flat, linear-flat, dome-shaped and semi-cylindrical-shaped. The optimization employs a statistical ray-tracing methodology of the incident light, mainly considering effects of chromatic aberration, varying focal lengths, solar inclination and azimuth angles, lens and receiver apertures, and the optimum number of prism grooves. While adopting an equal-groove-width assumption of the Poly-methyl-methacrylate (PMMA) prisms, the main target is to maximize the ray intensity on the receiver’s aperture and therefore achieving higher values of heat flux. The algorithm outputs prism angles and 2D sketches. 3D drawings are then generated via AutoCAD and linked to COMSOL Multiphysics software to simulate the lenses under solar ray conditions, which provides optical and thermal analysis at both the lens’ and the receiver’s apertures while setting conditions as per the Dallas-TX weather data. Once the lenses’ characterization is finalized, receivers are designed based on its optimized aperture size. Several cavity shapes; including triangular, arc-shaped and trapezoidal, are tested while coupled with a variety of receiver materials, working fluids, heat transfer mechanisms, and enclosure designs. A vacuum-reflective enclosure is also simulated for an enhanced thermal absorption efficiency. Each receiver type is simulated via COMSOL while coupled with the optimized lens. A lab-scale prototype for the optimum lens-receiver configuration is then fabricated for experimental evaluation. Application-based testing is also performed for the selected configuration, including that of a photovoltaic-thermal cogeneration system and solar furnace system. Finally, some future research work is pointed out, including the coupling of the collector-receiver system with an end-user power generator, and the use of a multi-layered genetic algorithm for comparative studies.

Keywords: COMSOL, concentrator, energy, fresnel, optics, renewable, solar

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Authors: I. Sinnarasa, Y. Thimont, L. Presmanes, A. Barnabé

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The thermoelectricity is a promising technique to overcome the issues in recovering waste heat to electricity without using moving parts. In fact, the thermoelectric (TE) effect defines as the conversion of a temperature gradient directly into electricity and vice versa. To optimize TE materials, the power factor (PF = σS² where σ is electrical conductivity and S is Seebeck coefficient) must be increased by adjusting the carrier concentration, and/or the lattice thermal conductivity Kₜₕ must be reduced by introducing scattering centers with point defects, interfaces, and nanostructuration. The PF does not show the advantages of the thin film because it does not take into account the thermal conductivity. In general, the thermal conductivity of the thin film is lower than the bulk material due to their microstructure and increasing scattering effects with decreasing thickness. Delafossite type oxides CuᴵMᴵᴵᴵO₂ received main attention for their optoelectronic properties as a p-type semiconductor they exhibit also interesting thermoelectric (TE) properties due to their high electrical conductivity and their stability in room atmosphere. As there are few proper studies on the TE properties of Mg-doped CuCrO₂ thin films, we have investigated, the influence of the annealing temperature on the electrical conductivity and the Seebeck coefficient of Mg-doped CuCrO₂ thin films and calculated the PF in the temperature range from 40 °C to 220 °C. For it, we have deposited Mg-doped CuCrO₂ thin films on fused silica substrates by RF magnetron sputtering. This study was carried out on 300 nm thin films. The as-deposited Mg doped CuCrO₂ thin films have been annealed at different temperatures (from 450 to 650 °C) under primary vacuum. Electrical conductivity and Seebeck coefficient of the thin films have been measured from 40 to 220 °C. The highest electrical conductivity of 0.60 S.cm⁻¹ with a Seebeck coefficient of +329 µV.K⁻¹ at 40 °C have been obtained for the sample annealed at 550 °C. The calculated power factor of optimized CuCrO₂:Mg thin film was 6 µW.m⁻¹K⁻² at 40 °C. Due to the constant Seebeck coefficient and the increasing electrical conductivity with temperature it reached 38 µW.m⁻¹K⁻² at 220 °C that was a quite good result for an oxide thin film. Moreover, the degenerate behavior and the hopping mechanism of CuCrO₂:Mg thin film were elucidated. Their high and constant Seebeck coefficient in temperature and their stability in room atmosphere could be a great advantage for an application of this material in a high accuracy temperature measurement devices.

Keywords: thermoelectric, oxides, delafossite, thin film, power factor, degenerated semiconductor, hopping mode

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Authors: Gonzalo Reyes, Magdalena Walczak, Esteban Ramos-Moore, Jorge Ramos-Grez

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Metal additive manufacture technologies have gained strong support and acceptance as a promising and alternative method to manufacture high performance complex geometry products. The main purpose of the present work is to study the microstructure and phase transformation temperatures of Cu-Al-Ni shape memory alloys fabricated from a direct laser additive process using metallic powders as precursors. The potential application is to manufacture self-centering seismic dampers for earthquake protection of buildings out of a copper based alloy by an additive process. In this process, the Cu-Al-Ni alloy is melted, inside of a high temperature and vacuum chamber with the aid of a high power fiber laser under inert atmosphere. The laser provides the energy to melt the alloy powder layer. The process allows fabricating fully dense, oxygen-free Cu-Al-Ni specimens using different laser power levels, laser powder interaction times, furnace ambient temperatures, and cooling rates as well as modifying concentration of the alloying elements. Two sets of specimens were fabricated with a nominal composition of Cu-13Al-3Ni and Cu-13Al-4Ni in wt.%, however, semi-quantitative chemical analysis using EDX examination showed that the specimens’ resulting composition was closer to Cu-12Al-5Ni and Cu-11Al-8Ni, respectively. In spite of that fact, it is expected that the specimens should still possess shape memory behavior. To confirm this hypothesis, phase transformation temperatures will be measured using DSC technique, to look for martensitic and austenitic phase transformations at 150°C. So far, metallographic analysis of the specimens showed defined martensitic microstructures. Moreover, XRD technique revealed diffraction peaks corresponding to (0 0 18) and (1 2 8) planes, which are too associated with the presence of martensitic phase. We conclude that it would be possible to obtain fully dense Cu-Al-Ni alloys having shape memory effect behavior by direct laser fabrication process, and to advance into fabrication of self centering seismic dampers by a controllable metal additive manufacturing process.

Keywords: Cu-Al-Ni alloys, direct laser fabrication, shape memory alloy, self-centering seismic dampers

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Authors: Javier Sánchez, Laura Elena De León Prado, Dora Alicia Cortés Hernández

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Magnetic spinel ferrites are materials that possess size, magnetic properties and heating ability adequate for their potential use in biomedical applications. The Mn_0.5Ga_0.5Fe₂O₄ magnetic nanoparticles (MNPs) were synthesized by sol-gel method using citric acid as chelating agent of metallic precursors. The synthesized samples were identified by X-Ray Diffraction (XRD) as an inverse spinel structure with no secondary phases. Saturation magnetization (Ms) of crystalline powders was 45.9 emu/g, which was higher than those corresponding to GaFe₂O₄ (14.2 emu/g) and MnFe₂O₄ (40.2 emu/g) synthesized under similar conditions, while the coercivity field (Hc) was 27.9 Oe. The average particle size was 18 ± 7 nm. The heating ability of the MNPs was enough to increase the surrounding temperature up to 43.5 °C in 7 min when a quantity of 4.5 mg of MNPs per mL of liquid medium was tested. Cytotoxic effect (hemolysis assay) of MNPs was determined and the results showed hemolytic values below 1% in all tested cases. According to the results obtained, these synthesized nanoparticles can be potentially used as thermoseeds for hyperthermia therapy.

Keywords: manganese-gallium ferrite, magnetic hyperthermia, heating ability, cytotoxicity

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Authors: Oleg Sokolov

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Despite the fact that the epoch of the Crusades ended more than 700 years ago, its legacy still remains relevant both in the Middle East and in the West. There was made a comparison of the positions of the most prominent Western and Arab medievalists of XX-XXI centuries, using the example of their interpretations of the success of the First Crusade. The analyzed corpus consists of 70 works. In the modern Arab Historiography, it is often pointed out that the Seljuks' struggle against the crusaders of the First Crusade was seriously hampered by the raids of the Arab Bedouin tribes of Jazira. At the same time, it is emphasized that the Arab rulers of Northern Syria were ‘pleased’ with the defeats of the Turks and made peace with the Crusaders, refusing to fight them. At the same time it is usually underlined that the Fatimid aggression against the Turks led both the first and the second to defeat from the Crusaders and became one of the main reasons for the success of the First Crusade and the Muslims' loss of Jerusalem in 1099. The position of Western historians about the reasons for the success of the First Crusade differs significantly. First of all, in the Western Historiography, it is noted that the deaths of the Fatimid and Abbasid Caliphs and the Seljuk Sultan between 1092 and 1094 years created political vacuum just before the crusaders appeared in the Middle East political arena. In 1097-1099, when the Crusaders advanced through Asia Minor, Syria and Palestine to Jerusalem, there was an active internecine struggle between the parts of the Seljuq state that had broken up by that time, and the crusaders were not perceived as a general threat of all Muslims of this region at that time. It is also pointed out that the main goals of the Crusaders - Antioch, Edessa, and Jerusalem - were at that time periphery since the main struggle for power in the Middle East was at this time in Iran. Thus, Arab historians see the lack of support from Arabs of Syria and Jazira and the aggression from Egypt as a crucial factors preventing the Seljuks from defeating the Crusaders, while their Western counterparts consider the internal power struggle between the Seljuks as a more important reason for the success of the First Crusade. The reason for this divergence in the treatment of the events of the First Crusade is probably the prevailing in much of Arab historiography, the idea of the Franks as an enemy of all peoples and religions of the Middle East. At the same time, in contemporary Western Historiography, the crusaders are described only as one of the many military and political forces that operated in this region at the end of the eleventh century.

Keywords: Arabs, Crusades, historiography, Turks

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Authors: Juliette Begin, Juliano Colapelle, Andrea Taratanu, Daniel Thirion, Amelie Marsot, Bryan A. Ross

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Chronic obstructive pulmonary disease (COPD), a leading cause of death globally, is characterized by chronic airflow obstruction and acute exacerbations (AECOPDs) that are often triggered by respiratory infections. Pseudomonas aeruginosa (P. aeruginosa), a potentially serious bacterial cause of AECOPDs, is treated with targeted anti-pseudomonal antibiotics. These select few antimicrobials are often used as first-line therapy in patients who are clinically unwell and/or in those suspected of P. aeruginosa-related infection prior to confirmation, potentially contributing to antimicrobial resistance. The present study evaluates prescribing practices in patients with a confirmed sputum history of P. aeruginosa admitted for AECOPD at the McGill University Health Centre (MUHC) and treated with anti-pseudomonal antibiotics. Serum antibiotic concentrations were measured from the same-day peak, trough, and mid-dose blood sampling intervals after reaching steady-state (on or after day 3) and were quantified using ultra-high-performance liquid chromatography (UHPLC). Demographic, clinical, and treatment outcomes were extracted from patient medical charts. Treatment failure was defined by respiratory-related death or mechanical ventilation after ≥3 days of antibiotics; antibiotic therapy extended beyond 2 weeks or a new antibiotic regimen started; or urgent care readmission within 30 days for AECOPD. To date, 9 of 30 planned participants have completed testing: seven received ciprofloxacin, one received meropenem, and one received piperacillin-tazobactam. Due to serum sample batching requirements, the serum ciprofloxacin concentration results for the first 2/8 participants are presented at the time of writing. The first participant had serum levels of 5.45mg/L (T₀), 4.74mg/L (T₅₀), and 4.49mg/L (T₁₀₀), while the second had serum levels of 5mg/L (T₀), 2.6mg/L (T₅₀), and 2.51mg/L (T₁₀₀). Pharmacokinetic parameters Cmax (5.18±0.43mg/L), T₁/₂ (23.56±18.94hours), and AUC (181.9±155.95mg*h/l) were higher than reported monograph values and met target AUC-to-MIC ratio of >125. The patients treated with meropenem and with piperacillin-tazobactam experienced treatment failure. Preliminary results suggest that standard ciprofloxacin dosing in patients experiencing an AECOPD and colonized with P. aeruginosa appears to achieve effective serum concentrations. Final cohort results will inform the pharmacokinetic appropriateness and clinical sufficiency of current AECOPD antimicrobial strategies in P. aeruginosa-colonized patients. This study will guide clinicians in determining the appropriate dosing for AECOPD treatment to achieve therapeutic levels, optimizing outcomes, and minimizing adverse effects. It could also highlight the value of routine antibiotic level monitoring in patients with treatment failure to ensure optimal serum concentrations.

Keywords: acute exacerbation, antimicrobial resistance, chronic obstructive pulmonary disease, pharmacokinetics/pharmacodynamics, Pseudomonas aeruginosa

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Mathilde Pavis

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From Schumann to Van Gogh, Frida Kahlo, and Ray Charles, the stories narrating the careers of artists with physical or mental disabilities are becoming increasingly popular. From the emergence of ‘pathography’ at the end of 18th century to cinematographic portrayals, the work and lives of differently-abled creative individuals continue to fascinate readers, spectators and researchers. The achievements of those artists form the tip of the iceberg composed of complex politico-cultural movements which continue to advocate for wider recognition of disabled artists’ contribution to western culture. This paper envisages copyright law as a potential tool to such end. It investigates the array of rights available to artists with intellectual disabilities to assert their position as authors of their artwork in the twenty-first-century looking at international and national copyright laws (UK and US). Put simply, this paper questions whether an artist’s intellectual disability could be a barrier to assert their intellectual property rights over their creation. From a legal perspective, basic principles of non-discrimination would contradict the representation of artists’ disability as an obstacle to authorship as granted by intellectual property laws. Yet empirical studies reveal that artists with intellectual disabilities are often denied the opportunity to exercise their intellectual property rights or any form of agency over their work. In practice, it appears that, unlike other non-disabled artists, the prospect for differently-abled creators to make use of their right is contingent to the context in which the creative process takes place. Often will the management of such rights rest with the institution, art therapist or mediator involved in the artists’ work as the latter will have necessitated greater support than their non-disabled peers for a variety of reasons, either medical or practical. Moreover, the financial setbacks suffered by medical institutions and private therapy practices have renewed administrators’ and physicians’ interest in monetising the artworks produced under their supervision. Adding to those economic incentives, the rise of criminal and civil litigation in psychiatric cases has also encouraged the retention of patients’ work by therapists who feel compelled to keep comprehensive medical records to shield themselves from liability in the event of a lawsuit. Unspoken transactions, contracts, implied agreements and consent forms have thus progressively made their way into the relationship between those artists and their therapists or assistants, disregarding any notions of copyright. The question of artists’ authorship finds itself caught in an unusually multi-faceted web of issues formed by tightening purse strings, ethical concerns and the fear of civil or criminal liability. Whilst those issues are playing out behind closed doors, the popularity of what was once called the ‘Art of the Insane’ continues to grow and open new commercial avenues. This socio-economic context exacerbates the need to devise a legal framework able to help practitioners, artists and their advocates navigate through those issues in such a way that neither this minority nor our cultural heritage suffers from the fragmentation of the legal protection available to them.

Keywords: authorship, copyright law, intellectual disabilities, art therapy and mediation

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Authors: A. N. Sharma

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A traditional medicine comprises a knowledge system, practices related to the cure of various ailments that developed over generations by indigenous people or populations. The indigenous populations developed a unique understanding with wild plants, herbs, etc., and earned specialized knowledge of disease pattern and curative therapy-though hard experiences, common sense, trial, and error methods. Here, an attempt has been made to study the possible aspects of traditional medicines for the enhancement of male sexual performance among the indigenous populations of Madhya Pradesh, India. Madhya Pradesh state is situated more or less in the central part of India. The data have been collected from the 305 Bharias of Patalkot, traditional health service providers of Sagar district, and other indigenous populations of Madhya Pradesh. It may be concluded that sizable traditional medicines exist in Madhya Pradesh, India, for the enhancement of male sexual performance, which still awaits for scientific exploration and intensive pharmaceutical investigations.

Keywords: Bharias, indigenous, Madhya Pradesh, sexual performance, traditional medicine

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Authors: David Parmenter, Brian Millar

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Obstructive sleep apnoea is a common condition which is generally under-diagnosed. Poorly managed obstructive sleep apnoea carries serious health risks and can greatly impact on the sufferer's quality of life. This publication covers the aetiology, symptoms, and treatment of sleep apnoea. The treatment of Obstructive Sleep Apnoea is an emerging field, and the useful role of the Dental Team is relatively unknown, therefor this paper will highlight the role of the dental team in its treatment. The concept of mandibular advancement appliances, along with the clinical and laboratory stages for constructing them, are documented. It is the hope of the author that this publication will educate healthcare professionals on the role of dental practitioners in the multidisciplinary team for treating sleep apnoea. Objective: Individuals should be more aware of the demographic of patients at risk of sleep apnoea, how it is diagnosed and which group of sleep apnoea patients are suitable to refer for mandibular appliance therapy. Individuals should also be aware of what a mandibular advancement appliance is and how it helps treat obstructive sleep apnoea.

Keywords: sleep apnoea, snoring, sleep appliances, mandibular advancement appliance

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Authors: Nautiyal Ruchira, Nautiyal Hemant, Chaudhury Devnanda, Bhargava Surbhi, Chauhan Nidhi

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Introduction: South East Asian region contributes 2.5 million cases of malaria each year to the global burden of 300 to 500 million of which 76% is reported from India. Government of India launched a national program almost half a century ago, still malaria remains a major public health challenge. Pregnant women are more susceptible to severe malaria and its fetomaternal complications. Inadequate surveillance and under-reporting underestimates the problem. Aim: Present study aimed to analyze the clinical course and pattern of malaria during pregnancy and to study the feto-maternal outcome. Methodology: This is a prospective observational study carried out at Himalayan Institute of Medical Sciences – a tertiary care center in the sub-Himalayan state of Uttarakhand, Northern India. All the pregnant women with malaria and its complications were recruited in the study during 2009 to 2014 which included referred cases from the state of western Uttar Pradesh. A thorough history and clinical examination were carried out to assess maternal and fetal condition. Relevant investigations including haemogram, platelet count, LFT, RFT, and USG was done. Blood slides and rapid diagnostic tests were done to diagnose the type of malaria.The primary outcomes measured were the type of malaria infection, maternal complications associated with malaria, outcome of pregnancy and effect on the fetus. Results: 67 antenatal cases with malaria infection were studied. 71% patients were diagnosed with plasmodium vivax infection, 25% cases were plasmodium falciparum positive and in 3% cases mixed infection was found. 38(56%) patients were primigravida and 29(43%) were multiparous. Most of the patients had already received some treatment from their local doctors and presented with severe malaria with the complications. Thrombocytopenia was the commonest manifestation seen in 35(52%) patients, jaundice in 28%, severe anemia in 18%, and severe oligohydramnios in 10% and renal failure in 6% cases. Regarding pregnancy outcome there were 44 % preterm deliveries, 22% had IUFD and abortions in 6% cases.20% of newborn were low birth weight and 6% were IUGR. There was only one maternal death which occurred due to ARDS in falciparum malaria. Although Plasmodium vivax was the main parasite considering the severity of clinical presentation, all the patients received intensive care. As most of the patients had received chloroquine therapy hence they were treated with IV artesunate followed by oral artemesinin combination therapy. Other therapies in the form of packed RBC’s and platelet transfusions, dialysis and ventilator support were provided when required. Conclusion: Even in areas with annual parasite index (API) less than 2 like ours, malaria in pregnancy could be an alarming problem. Vivax malaria cannot be considered benign in pregnancy because of high incidence of morbidity. Prompt diagnosis and aggressive treatment can reduce morbidity and mortality significantly. Increased community level research, integrating ANC checkups with the distribution of insecticide-treated nets in areas of high endemicity, imparting education and awareness will strengthen the existing control strategies.

Keywords: severe malaria, pregnancy, plasmodium vivax, plasmodium falciparum

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Authors: Ammal Mokhtar Metwally, Amal Elsaied, Ghada A. Abdel-Latef, Ebtissam M. Salah El-Din, Hanaa R. M. Attia

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The link between various diet therapies and autism is controversial and limited. Nutritional interventions aim to increase antioxidant levels suggesting a positive effect on the improvement of autism severity. In this study, the effectiveness of a 90-day Dates fruits consumption fruits (a non-pharmacological and risk-free option) on alleviating autism severity symptoms in individuals with ASD was investigated. The study examined also whether the baseline or improvements of some of the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake on the severity of ASD symptoms. Methodology: This study involved a randomized controlled, double-blind 3-month dates fruits intake. 131 Egyptian children aged 3-12 years with confirmed ASD were enrolled in the study. cases were randomized in one of the three groups as follows; 1st regimen: Group I on 3 dates’ fruits/day (47 cases), 2nd regimen: Group II on 5 dates’ fruits/day (42 cases), and 3rd regimen: group III; nondates group (42 cases). ASD severity was assessed using both the Diagnostic and statistical manual of mental disorders, 5th ed. (DSM-V) criteria and the Childhood Autism Rating Scale (CARS) analysis. The following measures were assessed before and after the regimens: blood levels of three oxidative markers; Malondialdehyde (MDA), glutathione peroxidase (GPX1), and superoxide dismutase (SOD), nutritional, dietary assessment & anthropometric measurements Results: A significant reduction in the mean score of autism was detected based on CARS scores for those on dates’ regimens compared to those on non-dates (p < 0.01). Participants on 5 dates’ fruits/day for three months showed the highest improvement for autism severity based on both CARS and DSM5 compared to those in 3 dates’ fruits/day and non-dates groups. Responders to dates fruits intake as reflected on the Improvement of autism severity based on CARS diagnosis was detected among 78.7 % and 62.9 % based on CARS and DSM5 diagnosis, respectively. Responders had significant improvement in BMI z score and in the ratio levels of both MDA/SOD and MDA/GPX. Conclusion: The positive results of this study suggest that palm dates fruits could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms Objective: Investigate the effectiveness of a 90-day Dates fruits consumption fruits on alleviating autism severity symptoms in individuals with ASD and explore the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake. Methodology: The study was a randomized controlled, double-blind for 3-month. 131 autistic Egyptian children aged 3-12 years were enrolled in one of the three groups; 1st: on 3 dates’ fruits/day (47 cases), 2nd: Group II on 5 dates’ fruits/day (42 cases), and 3rd: group III; nondates group (42 cases). Conclusion: The positive results of this study suggest that palm dates fruit (a non-pharmacological and risk-free option) could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms.

Keywords: autism spectrum disorders, palm dates fruits, CARS, DSM5, oxidative markers

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Authors: P. S. Jagadeesh Kumar, Tracy Lin Huan, S. Meenakshi Sundaram

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Alzheimer’s disease is one of the prevalent kind of ailment, expected for impudent reconciliation or an effectual therapy is to be accredited hitherto. Probable detonation of patients in the upcoming years, and consequently an enormous deal of apprehension in early discovery of the disorder, this will conceivably chaperon to enhanced healing outcomes. Complex impetuosity of the brain is an observant symbolic of the disease and a unique recognition of genetic sign of the disease. Machine learning alongside deep learning and decision tree reinforces the aptitude to absorb characteristics from multi-dimensional data’s and thus simplifies automatic classification of Alzheimer’s disease. Susceptible testing was prophesied and realized in training the prospect of Alzheimer’s disease classification built on machine learning advances. It was shrewd that the decision trees trained with deep neural network fashioned the excellent results parallel to related pattern classification.

Keywords: Alzheimer's diagnosis, decision trees, deep neural network, machine learning, pattern classification

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Authors: Athanasia Kouroupa, Karen Irvine, Sivana Mengoni, Shivani Sharma

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Exploring parents’ preferences towards technology-based interventions for children on the autism spectrum can inform future research and support technology design. The study aimed to provide a comprehensive description of parents’ knowledge and preferences about innovative technology to support children on the autism spectrum. Survey data were collected from parents (n = 267) internationally. The survey included information about the use of conventional (e.g., smartphone, iPod, tablets) and non-conventional (e.g., virtual reality, robot) technologies. Parents appeared to prefer conventional technologies such as tablets and dislike non-conventional ones. They highlighted the positive contribution technology brought to the children’s lives during the pandemic. A few parents were equally concerned that the compulsory introduction of technology during the pandemic was associated with elongated time on devices. The data suggested that technology-based interventions are not widely known, need to be financially approachable and achieve a high standard of design to engage users.

Keywords: autism, intervention, preferences, technology

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Authors: Vinesh Janarthanan, Mohammad H. Rahman

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There are numerous neurological conditions that may result in a loss of motor function. Such conditions may include cerebral palsy, Parkinson’s disease, stroke or multiple sclerosis. Due to impaired motor function, specifically in the hand and arm, living independently becomes tremendously more difficult. Rehabilitation programs are the main method to treat these kinds of disabled individuals. However, these programs require longtime commitment from the clinicians/therapists, demand person to person caring, and typically the treatment duration is usually very long. Aside from the treatment received from the therapist, the continuation of neuroplasticity at home is essential to maximizing development and restoring the biological function. To contribute in this area, we have researched and developed a portable and comfortable hand glove for fine motor skills rehabilitation. The glove provides interactive home-based therapy to engage the patient with simple games. The key to this treatment is the repetition of moving the hand and being capable of positioning the hand in various ways.

Keywords: home based, wearable sensors, glove, rehabilitation, motor function, video games

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Authors: Kira Merigan

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BACKGROUND- Fertility preservation (FP) measures are increasingly recognised as an important consideration for children and adolescents planned to undergo potentially damaging gonadotoxic therapy. Worldwide, there are very few documented cases of FP in young females by way of ovarian stimulation and oocyte cryopreservation.AIM – To report a case series of mature oocyte cryopreservation in 5post-pubertal adolescents aged 14-17 years old, with varied medical conditions requiring gonadotoxic treatment. SETTING-These cases took place via a multidisciplinary team approach at The Royal Children’s Hospital, a large tertiary centre in Melbourne, Australia. INTERVENTION– Ovarian stimulation and oocyte collection was performed as detailed in each case. RESULTS –Across the 5 patients, 3-28 oocytes were retrieved. We report pre-treatment workup, complications, and delays to treatment. CONCLUSION- Oocyte cryopreservation may be a safe alternative to ovarian tissue cryopreservation (OTC) in the adolescent population

Keywords: fertility preservation, adolescent, ovarian stimulation, oocyte cryopreservation

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Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: Aref Lashin

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Saudi Arabia vision of 2030 calls for the diversification of energy sources in the Kingdom. Accordingly, Saudi Arabia has launched a promising plan aims to gradually power the major industrial activities in country by renewable and low carbon energy sources. The geothermal sources are among the promising renewable sources that can support the achievement of the country vision and energy mix plan. Saudi Arabia is enriched with several geothermal resources especially in the western and southwestern regions along the Red Sea region. This paper will give an overview on the different geothermal resources (Hydrothermal, Harrats volcanic eruptions and hot dry rocks) of Saudi Arabia, their categories and classifications as well as the different exploration (Geophysical, geological, geochemical, etc) and drilling enhanced during the last few decades. The economic viability and the possible contribution of geothermal resources in the future of renewable energy of Saudi Arabia is discussed. Some case studies from Jizan, Al-Lith, Harrats and Midyan areas are demonstrated. Scenarios of different low and high geothermal applications for possible power generations, as well as other low-grade utilizations, e.g. direct use, district heating & cooling, medical therapy, etc., are presented.

Keywords: KSA vison 2023, energy mix, geothermal resources, applications, Saudi Arabia

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Authors: Alireza Moghtaderi, Negin Khakpour

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Disc Herniation is a common complication in the society and it is one of the main reasons for referring to physical medicine and rehabilitation clinics. Despite of various methods proposed for treatingthis disease, still there is disagreement on success of these methods especially in non-surgical methods, and thus current study aims at determining effect of laser beam and magnet on treatment of Intervertebral Disc Herniation. During a clinical trial study, 80 patients with Intervertebral Disc Herniation underwent a combined package of treatment including magnet, laser beam, PRP and Prolotherapy during 6 months. Average age of patients was 51.25 ± 10.7 with range of 25 – 71 years. 30 men (37.5%) and 50 women (62.5%) took part in the study. average weight of patients was 64.3 ± 7.2 with range of 49 – 79 kg. highest level of Disc Herniation was L5 – S1 with frequency of 17 cases (21.3%). Disc Herniation was severe in 30 cases before treatment, but it reduced to 3 casesafter treatment. This study indicates effect of combined treatment using non-invasive laser beam and magnet therapy on disco genic diseases and mechanical pains of spine is highly effective.

Keywords: hallux, valgus, botulinum toxin a, pain

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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Authors: Tanveer Beg, Yasir H. Siddique, Gulshan Ara, Asfar S. Azmi, Mohammad Afzal

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Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protective mechanism of action and genistein from soy is recognized as an anti-oxidant with similar properties. Therefore, the present study investigates the effect of genistein against the genotoxic doses of doxorubicin by assessing chromosomal aberrations, sister chromatid exchanges, cell cycle kinetics, cell viability, apoptosis, and DNA damage markers in cultured human lymphocytes. Our results reveal that genistein treatment significantly suppresses genotoxic damage induced by doxorubicin. It is concluded that genistein has the potential to reduce the genotoxicity induced by anti-cancer drugs, thereby reducing the chances of developing secondary tumors during the therapy.

Keywords: apoptosis, DNA damage markers, doxorubicin, genistein, genotoxicity, human lymphocyte culture

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Authors: S. Zolghadri, M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani

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In this study, the absorbed dose of human organs after injection of ¹⁷⁷Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, ¹⁷⁷Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: ¹⁷⁷Lu, breast cancer, compartmental modeling, dosimetry

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Authors: Benedikt Munzar, Jagraj Singh, Alice Mei, David Musheyev, Sandeep Gandhi

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Clostridium is a gram-positive, anaerobic, spore-forming rod that is not commonly identified as a primary human pathogen. Here is presented a case of a 60-year-old patient with a history of opioid use disorder who underwent a number of abdominal surgeries for small bowel obstruction. His hospital course was complicated by Clostridium glycolicum infection, resulting in an acute abdomen. The patient clinically improved with antibiotic therapy. A thorough review of the National Institute of Health database revealed that only a small number of cases have been reported since 2007, with the last postsurgical cases documented in 2009 and the last clinical case documented in 2012. Clostridium glycolicum infections have been noted in patients with immunosuppressive conditions or those undergoing medical treatments that compromise immune function. This case was unusual due to the patient being immunocompetent. We suggest that a case of an acute abdomen should consider this organism as an etiological agent.

Keywords: acute abdomen, bacterial infection, clostridium glycolicum, Meckel’s diverticulum, pneumoperitoneum, small bowel obstruction

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Authors: Karim Mohamed Fawzy Ghuiba, Alaa Aldeen Abd Al Hakeem Balbaa, Shams Elbaz

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Objectives: To compare between the effects continuous and pulsed ultrasound on pain and function in patient with knee osteoarthritis. Design: Randomized-Single blinded Study. Participants: 6 patients with knee osteoarthritis with mean age 53.66±3.61years, Altman Grade II or III. Interventions: Subjects were randomly assigned into two groups; Group A received continuous ultrasound and Group B received pulsed ultrasound. Outcome measures: Effects of pulsed and continuous ultrasound were evaluated by pain threshold assessed by visual analogue scale (VAS) scores and function assessed by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores. Results: There was no significant decrease in VAS and WOMAC scores in patients treated with pulsed or continuous ultrasound; and there were no significant differences between both groups. Conclusion: there is no difference between the effects of pulsed and continuous ultrasound in pain relief or functional outcome in patients with knee osteoarthritis.

Keywords: knee osteoarthritis, pulsed ultrasound, ultrasound therapy, continuous ultrasound

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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