Search results for: antimicrobial agents

Authors: S. N. T. I. Sampath, J. M. S. Jayasinghe, A. P. Attanayake, V. Karunaratne

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Diabetes mellitus is one of the major public health posers throughout the world today that incidence and associated with increasing mortality. Insufficient regulation of the blood glucose level might be serious effects for health and its necessity to identify new therapeutics that have ability to reduce hyperglycaemic condition in the human body. Even though synthetic antidiabetic drugs are more effective to control diabetes mellitus, there are considerable side effects have been reported. Thus, there is an increasing demand for searching new natural products having high antidiabetic activity with lesser side effects. The purposes of the present study were to evaluate different physical parameters and in-vitro and in-vivo antidiabetic potential of the selected combined medicinal plant extracts mixture composed of leaves of Murraya koenigii, cloves of Allium sativum, fruits of Garcinia queasita and seeds of Piper nigrum. The selected plants parts were mixed and ground together and extracted sequentially into the hexane, ethyl acetate and methanol. Solvents were evaporated and they were further dried by freeze-drying to obtain a fine powder of each extract. Various physical parameters such as moisture, total ash, acid insoluble ash and water soluble ash were evaluated using standard test procedures. In-vitro antidiabetic activity of combined plant extracts mixture was screened using enzyme assays such as α-amylase inhibition assay and α-glucosidase inhibition assay. The acute anti-hyperglycaemic activity was performed using oral glucose tolerance test for the streptozotocin induced diabetic Wistar rats to find out in-vivo antidiabetic activity of combined plant extracts mixture and it was assessed through total oral glucose tolerance curve (TAUC) values. The percentage of moisture content, total ash content, acid insoluble ash content and water soluble ash content were ranged of 7.6-17.8, 8.1-11.78, 0.019-0.134 and 6.2-9.2 respectively for the plant extracts and those values were less than standard values except the methanol extract. The hexane and ethyl acetate extracts exhibited highest α-amylase (IC50 = 25.7 ±0.6; 27.1 ±1.2 ppm) and α-glucosidase (IC50 = 22.4 ±0.1; 33.7 ±0.2 ppm) inhibitory activities than methanol extract (IC50 = 360.2 ±0.6; 179.6 ±0.9 ppm) when compared with the acarbose positive control (IC50 = 5.7 ±0.4; 17.1 ±0.6 ppm). The TAUC values for hexane, ethyl acetate, and methanol extracts and glibenclamide (positive control) treated rats were 8.01 ±0.66; 8.05 ±1.07; 8.40±0.50; 5.87 ±0.93 mmol/L.h respectively, whereas in diabetic control rats the TAUC value was 13.22 ±1.07 mmol/L.h. Administration of plant extracts treated rats significantly suppressed (p<0.05) the rise in plasma blood glucose levels compared to control rats but less significant than glibenclamide. The obtained results from in-vivo and in-vitro antidiabetic study showed that the hexane and ethyl acetate extracts of selected combined plant mixture might be considered as a potential source to isolate natural antidiabetic agents and physical parameters of hexane and ethyl acetate extracts will helpful to develop antidiabetic drug with further standardize properties.

Keywords: diabetes mellitus, in-vitro antidiabetic assays, medicinal plants, standardization

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Authors: Mostafa Feiz, Hossein Hadizadeh, Mohammad Safari

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The Chalpo copper area is located in northeastern Iran, which is part of the structural zone of central Iran and the back-arc basin of Sabzevar. This sedimentary basin accumulated in destructive-Oligomiocene sediments is named the Nasr-Chalpo-Sangerd (NCS) basin. The sedimentary layers in this basin originated mainly from Upper Cretaceous ophiolitic rocks and intermediate to mafic-post ophiolitic volcanic rocks, deposited as a nonconformity. The mineralized sandstone layers in the Chalpo area include leached zones (with a thickness of 5 to 8 meters) and mineralized lenses with a thickness of 0.5 to 0.7 meters. Ore minerals include primary sulfide minerals, such as chalcocite, chalcopyrite, and pyrite, as well as secondary minerals, such as covellite, digenite, malachite, and azurite, formed in three stages that comprise primary, simultaneously, and supergene stage. The best agents that control the mineralization in this area include the permeability of host rocks, the presence of fault zones as the conduits for copper oxide solutions, and significant amounts of plant fossils, which create a reducing environment for the deposition of mineralized layers. Statistical studies on copper layers indicate that Ag, Cd, Mo, and S have the maximum positive correlation with Cu, whereas TiO₂, Fe₂O₃, Al₂O₃, Sc, Tm, Sn, and the REEs have a negative correlation. The calculations of mass changes on copper-bearing layers and primary sandstone layers indicate that Pb, As, Cd, Te, and Mo are enriched in the mineralized zones, whereas SiO₂, TiO₂, Fe₂O₃, V, Sr, and Ba are depleted. The combination of geological, stratigraphic, and geochemical studies suggests that the origin of copper may have been the underlying red strata that contained hornblende, plagioclase, biotite, alkaline feldspar, and labile minerals. Dehydration and hydrolysis of these minerals during the diagenetic process caused the leaching of copper and associated elements by circling fluids, which formed an oxidant-hydrothermal solution. Copper and silver in this oxidant solution might have moved upwards through the basin-fault zones and deposited in the reducing environments in the sandstone layers that have had abundant organic matters. Copper in these solutions probably was carried by chloride complexes. The collision of oxidant and reduced solutions caused the deposition of Cu and Ag, whereas some stable elements in oxidant environments (e.g., Fe₂O₃, TiO₂, SiO₂, REEs) become unstable in the reduced condition. Therefore, the copper-bearing sandstones in the study area are depleted from these elements resulting from the leaching process. The results indicate that during the mineralization stage, LREEs and MREEs were depleted, but Cu, Ag, and S were enriched. Based on field evidence, it seems that the circulation of connate fluids in the reb-bed strata, produced by diagenetic processes, encountered to reduced facies, which formed earlier by abundant fossil-plant debris in the sandstones, is the best model for precipitating sulfide-copper minerals.

Keywords: Chalpo, oligo-miocene red beds, sandstone-hosted copper mineralization, mass change, LREEs, MREEs

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Authors: Marie-Helena Docherty, Sion Edryd Williams

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The prevalence of diabetes mellitus is increasing worldwide. In Sub-Saharan Africa, type 2 diabetes represents over 90% of all types of diabetes with the number of diabetic patients expected to rise. This represents a huge economic burden in an area already contending with high rates of other significant diseases, including the highest worldwide prevalence of HIV. Diabetic complications considerably impact on morbidity and mortality. The epidemiological data for the region quotes high rates of retinopathy (7-63%), neuropathy (27-66%) and microalbuminuria (10-83%). It is therefore imperative that diabetic screening programmes are established. It is recognised that in many parts of the developing world the implementation and management of such programmes is limited by a lack of available resources. The International Diabetes Federation produced guidelines in 2012 taking these limitations into account suggesting that all diabetic patients should have access to basic screening. These guidelines are consistent with the national diabetic guidelines produced by the Lesotho Medical Council. However, diabetic care in Lesotho is delivered at the local level, with variable levels of quality. A cross sectional study was performed in the outpatient department of Maluti Hospital in Mapoteng, Lesotho, a busy rural hospital in the Berea district. Demographic data on gender, age and modality of treatment were collected over a six-week time period. Information regarding 3 basic screening parameters was obtained. These parameters included eye screening (defined as a documented ophthalmology review within the last 12 months), foot screening (defined as a documented foot health assessment by any health care professional within the last 12 months) and secondary prevention (defined as a documented blood pressure and lipid profile reading within the last 12 months). These parameters were selected on the basis of the absolute minimum level of resources in Maluti Hospital. Renal screening was excluded, as the hospital does not have access to reliable renal profile checks or urinalysis. There is however a fully functioning on-site ophthalmology department run by a senior ophthalmologist with the ability to provide retinal photography, retinal surgery and photocoagulation therapy. Data was collected on 183 type 2 diabetics. 112 patients were male and 71 were female. The average age was 43 years. 4 patients were diet controlled, 140 patients were on oral hypoglycaemic agents (metformin and/or glibenclamide), and 39 patients were on a combination of insulin and oral hypoglycaemics. In the preceding 12 months, 5 patients had undergone eye screening (3%), 24 patients had undergone foot screening (13%), and 31 patients had lipid profile testing (17%). All patients had a documented blood pressure reading (100%). Our results show that screening is poorly performed in the basic indicators suggested by the IDF and the Lesotho Medical Council. On the basis of these results, a screening programme was developed using the mnemonic SaFE; secondary prevention, foot and eye care. This is simple, memorable and transferable between healthcare professionals. In the future, the expectation would be to expand upon this current programme to include renal screening, and to further develop screening pertaining to secondary prevention.

Keywords: Africa, complications, rural, screening

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Authors: Nikolaus Wilke, Boaz Paz

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Museum staff, conservators, restorers, curators, registrars, art handlers but potentially also museum visitors are often exposed to the harmful effects of biocides, which have been applied to collections in the past for the protection and preservation of cultural heritage. Due to stable light, moisture, and temperature conditions, the biocidal active ingredients were preserved for much longer than originally assumed by chemists, pest controllers, and museum scientists. Given the requirements to minimize the use and handling of toxic substances and the obligations of employers regarding safe working environments for their employees, but also for visitors, the museum sector worldwide needs adequate decontamination solutions. Today there are millions of contaminated objects in museums. This paper introduces the results of a systematic investigation into the reduction rate of biocide contamination in various organic materials that were treated with the humidity and temperature controlled ICM (Integrated Contamination Management) method. In the past, collections were treated with a wide range, at times even with a combination of toxins, either preventively or to eliminate active insect or fungi infestations. It was only later that most of those toxins were recognized as CMR (cancerogenic mutagen reprotoxic) substances. Among them were numerous chemical substances that are banned today because of their toxicity. While the biocidal effect of inorganic salts such as arsenic (arsenic(III) oxide), sublimate (mercury(II) chloride), copper oxychloride (basic copper chloride) and zinc chloride was known very early on, organic tar distillates such as paradichlorobenzene, carbolineum, creosote and naphthalene were increasingly used from the 19th century onwards, especially as wood preservatives. With the rapid development of organic synthesis chemistry in the 20th century and the development of highly effective warfare agents, pesticides and fungicides, these substances were replaced by chlorogenic compounds (e.g. γ-hexachlorocyclohexane (lindane), dichlorodiphenyltrichloroethane (DDT), pentachlorophenol (PCP), hormone-like derivatives such as synthetic pyrethroids (e.g., permethrin, deltamethrin, cyfluthrin) and phosphoric acid esters (e.g., dichlorvos, chlorpyrifos). Today we know that textile artifacts (costumes, uniforms, carpets, tapestries), wooden objects, herbaria, libraries, archives and historical wall decorations made of fabric, paper and leather were also widely treated with toxic inorganic and organic substances. The migration (emission) of pollutants from the contaminated objects leads to continuous (secondary) contamination and accumulation in the indoor air and dust. It is important to note that many of mentioned toxic substances are also material-damaging; they cause discoloration and corrosion. Some, such as DDT, form crystals, which in turn can cause micro tectonic, destructive shifting, for example, in paint layers. Museums must integrate sustainable solutions to address the residual biocide problems already in the planning phase. Gas and dust phase measurements and analysis must become standard as well as methods of decontamination.

Keywords: biocides, decontamination, museum collections, toxic substances in museums

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Authors: Felix Darko-Amoah, Daniel Acquah

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In contemporary ecosystems for developing countries like Ghana, the need to explore innovative solutions for sustainable livelihoods of farmers is more important than ever. With Ghana’s population growing steadily and the demand for food, fiber and shelter increasing, it is imperative that the construction industry and agriculture come together to address the challenges faced by farmers in the country. In order to enhance the livelihoods of cocoa farmers in Ghana, this paper provides an innovative strategy that aims to integrate the areas of civil engineering and cash crop agriculture. This study focuses on cocoa cultivation in poorer nations, where farmers confront a variety of difficulties include restricted access to financing, subpar infrastructure, and insufficient support services. We seek to improve farmers' access to financing, improve infrastructure, and provide support services that are essential to their success by combining the fields of building engineering and cocoa production. The findings of the study are beneficial to cocoa producers, community extension agents, and construction engineers. In order to accomplish our objectives, we conducted 307 of field investigations in particular cocoa growing communities in the Western Region of Ghana. Several studies have shown that there is a lack of adequate infrastructure and financing, leading to low yields, subpar beans, and low farmer profitability in developing nations like Ghana. Our goal is to give farmers access to better infrastructure, better financing, and support services that are crucial to their success through the fusion of construction engineering and cocoa production. Based on data gathered from the field investigations, the results show that the employment of appropriate technology and methods for developing structures, roads, and other infrastructure in rural regions is one of the essential components of this strategy. For instance, we find that using affordable, environmentally friendly materials like bamboo, rammed earth, and mud bricks can assist to cut expenditures while also protecting the environment. By applying simple relational techniques to the data gathered, the results also show that construction engineers are crucial in planning and building infrastructure that is appropriate for the local environment and circumstances and resilient to natural disasters like floods. Thus, the convergence of construction engineering and cash crop cultivation is another crucial component of the agriculture-construction interplay. For instance, farmers can receive financial assistance to buy essential inputs, such as seeds, fertilizer, and tools, as well as training in proper farming methods. Moreover, extension services can be offered to assist farmers in marketing their crops and enhancing their livelihoods and revenue. In conclusion, our analysis of responses from the 307 participants depicts that the combination of construction engineering and cash crop agriculture offers an innovative approach to improving farmers' livelihoods in cocoa farming communities in Ghana. In conclusion, by inculcating the findings of this study into core decision-making, policymakers can help farmers build sustainable and profitable livelihoods by addressing challenges such as limited access to financing, poor infrastructure, and inadequate support services.

Keywords: cocoa agriculture, construction engineering, farm buildings and equipment, improved livelihoods of farmers

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Francesca Gullo, Paola Palmero, Massimo Messori

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Transparent wood is considered a promising structural material for the development of environmentally friendly, energy-efficient engineered components. To obtain transparent wood from natural wood materials two approaches can be used: i) bottom-up and ii) top-down. Through the second method, the color of natural wood samples is lightened through a chemical bleaching process that acts on chromophore groups of lignin, such as the benzene ring, quinonoid, vinyl, phenolics, and carbonyl groups. These chromophoric units form complex conjugate systems responsible for the brown color of wood. There are two strategies to remove color and increase the whiteness of wood: i) lignin removal and ii) lignin bleaching. In the lignin removal strategy, strong chemicals containing chlorine (chlorine, hypochlorite, and chlorine dioxide) and oxidizers (oxygen, ozone, and peroxide) are used to completely destroy and dissolve the lignin. In lignin bleaching methods, a moderate reductive (hydrosulfite) or oxidative (hydrogen peroxide) is commonly used to alter or remove the groups and chromophore systems of lignin, selectively discoloring the lignin while keeping the macrostructure intact. It is, therefore, essential to manipulate nanostructured wood by precisely controlling the nanopores in the cell walls by monitoring both chemical treatments and process conditions, for instance, the treatment time, the concentration of chemical solutions, the pH value, and the temperature. The elimination of wood light scattering is the second step in the fabrication of transparent wood materials, which can be achieved through two-step approaches: i) the polymer impregnation method and ii) the densification method. For the polymer impregnation method, the wood scaffold is treated with polymers having a corresponding refractive index (e.g., PMMA and epoxy resins) under vacuum to obtain the transparent composite material, which can finally be pressed to align the cellulose fibers and reduce interfacial defects in order to have a finished product with high transmittance (>90%) and excellent light-guiding. However, both the solution-based bleaching and the impregnation processes used to produce transparent wood generally consume large amounts of energy and chemicals, including some toxic or pollutant agents, and are difficult to scale up industrially. Here, we report a method to produce optically transparent wood by modifying the lignin structure with a chemical reaction at room temperature using small amounts of hydrogen peroxide in an alkaline environment. This method preserves the lignin, which results only deconjugated and acts as a binder, providing both a strong wood scaffold and suitable porosity for infiltration of biobased polymers while reducing chemical consumption, the toxicity of the reagents used, polluting waste, petroleum by-products, energy and processing time. The resulting transparent wood demonstrates high transmittance and low thermal conductivity. Through the combination of process efficiency and scalability, the obtained materials are promising candidates for application in the field of construction for modern energy-efficient buildings.

Keywords: bleached wood, energy-efficient components, hydrogen peroxide, transparent wood, wood composites

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Authors: Jiri Nepereny, Vladimir Vrzal

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Staphylococcus intermedius/pseudintermedius bacteria are commonly found on the skin of healthy dogs and can cause pruritic skin diseases under certain circumstances (trauma, allergy, immunodeficiency, ectoparasitosis, endocrinological diseases, glucocorticoid therapy, etc.). These can develop into complicated superficial or deep pyoderma, which represent a large group of problematic skin diseases in dogs. These are predominantly inflammations of a secondary nature, associated with the occurrence of coagulase-positive Staphylococcus spp. A major problem is increased itching, which greatly complicates the healing process. The aim of this work is to verify the efficacy of the developed preparation Bacteriophage SI (Staphylococcus intermedius). The tested preparation contains a lysate of bacterial cells of S. intermedius host culture including culture medium and live virions of specific phage. Sodium Merthiolate is added as a preservative in a safe concentration. Validation of the efficacy of the product was demonstrated by monitoring the therapeutic effect after application to indicated cases from clinical practice. The indication for inclusion of the patient into the trial was an adequate history and clinical examination accompanied by sample collection for bacteriological examination and isolation of the specific causative agent. Isolate identification was performed by API BioMérieux identification system (API ID 32 STAPH) and rep-PCR typing. The suitability of therapy for a specific case was confirmed by in vitro testing of the lytic ability of the bacteriophage to lyse the specific isolate = formation of specific plaques on the culture isolate on the surface of the solid culture medium. So far, a total of 32 dogs of different sexes, ages and breed affiliations with different symptoms of staphylococcal dermatitis have been included in the testing. Their previous therapy consisted of more or less successful systemic or local application of broad-spectrum antibiotics. The presence of S. intermedius/pseudintermedius has been demonstrated in 26 cases. The isolates were identified as a S. pseudintermedius, in all cases. Contaminant bacterial microflora was always present in the examined samples. The test product was applied subcutaneously in gradually increasing doses over a period of 1 month. After improvement in health status, maintenance therapy was followed by application of the product once a week for 3 months. Adverse effects associated with the administration of the product (swelling at the site of application) occurred in only 2 cases. In all cases, there was a significant reduction in clinical signs (healing of skin lesions and reduction of inflammation) after therapy and an improvement in the well-being of the treated animals. A major problem in the treatment of pyoderma is the frequent resistance of the causative agents to antibiotics, especially the increasing frequency of multidrug-resistant and methicillin-resistant S. pseudintermedius (MRSP) strains. Specific phagolysate using for the therapy of these diseases could solve this problem and to some extent replace or reduce the use of antibiotics, whose frequent and widespread application often leads to the emergence of resistance. The advantage of the therapeutic use of bacteriophages is their bactericidal effect, high specificity and safety. This work was supported by Project FV40213 from Ministry of Industry and Trade, Czech Republic.

Keywords: bacteriophage, pyoderma, staphylococcus spp, therapy

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Authors: Md. Nuru Miah, A. F. M. Akhter Uddin

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Medicinal plants are grown naturally in a tropical environment in Bangladesh and used as drug and therapeutic agents in the health care system. According to Bangladesh Agricultural Research Institute (BARI), there are 722 species of medicinal plants in the country. Of them, 255 plants are utilized by the manufacturers of Ayurvedic and Unani medicines. Medicinal plants like Aloevera, Ashwagonda, shotomul,Tulsi, Vuikumra, Misridana are extensively cultivated in some selected areas as well; where Aloevera scored the highest position in production. In the early 1980, Ayurvedic and Unani companies procured 80 percent of medicinal plants from natural forests, and the rest 20 percent was imported. Now the scenario has changed; 80 percent is imported, and the rest 20 percent is collected from local products(Source: Astudy on sectorbased need assessment of Business promotion council-Herbal products and medicinal plants, page-4). Uttara Development Program Society, a leading Non- Government development organization in Bangladesh, has been implementing a value chain development project under promoting Agricultural commercialization and Enterprises of Pally Karma Sahayak Foundation (PKSF) funded by the International Fund for Agricultural Development (IFAD) in Natore Sadar Upazila from April 2017 to sustainably develop the technological interventions for products and market development. The ultimate goal of the project is to increase income, generate employment and develop this sector as a sustainable business enterprise. Altogether 10,000 farmers (Nursery owners, growers, input supplier, processors, whole sellers, and retailers) are engaged in different activities of the project. The entrepreneurs engaged in medicinal plant cultivation did not know and follow environmental and good agricultural practices. They used to adopt traditional methodology in production and processing. Locally the farmers didn’t have any positive initiative to expand their business as well as developvalue added products. A lot of diversified products could be possible to develop and marketed with the introduction of post-harvest processing technology and market linkage with the local and global buyer. Training is imparted to the nursery owners and herbal growers on production technologies, sowing method, use of organic fertilizers/compost/pesticides, harvesting procedures, and storage facilities. Different types of herbal tea like Rosella, Moringa, Tulshi, and Basak are being produced and packed locally with a good scope of its marketing in different cities of the country. The project has been able to achieve a significant impact in the development of production technologies, but still, there is room for further improvement in processing, packaging, and marketing level. The core intervention of the current project to develop some entrepreneurs for branding, packaging, promotion, and marketing while considering environment friendly practices. The present strategies will strengthen the knowledge and skills of the entrepreneurs for the production and marketing of their products, maintaining worldwide accepted compliance system for easy access to the global market.

Keywords: aloe vera, herbs and shrubs, market, interventions

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Authors: Mary Katherine Hoth

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Despite racial and ethnic disparities in American psychiatry being well-documented, there remains an apathetic attitude among nurses and providers within the field to engage in active antiracism and provide equitable, recovery-oriented care. It is insufficient to be a “colorblind” nurse or provider and state that call care provided is identical for every patient. Maintaining an attitude of “colorblindness” perpetuates the racism prevalent throughout healthcare and leads to negative patient outcomes. The purpose of this literature review is to highlight the how the historical beginnings of psychiatry have evolved into the disparities seen in today’s practice, as well as to provide some insight on methods that providers and nurses can employ to actively participate in challenging these racial disparities. Background The application of psychiatric medicine to White people versus Black, Indigenous, and other People of Color has been distinctly different as a direct result of chattel slavery and the development of pseudoscience “diagnoses” in the 19th century. This weaponization of the mental health of Black people continues to this day. Population The populations discussed are Black, Indigenous, and other People of Color, with a primary focus on Black people’s experiences with their mental health and the field of psychiatry. Methods A literature review was conducted using CINAHL, EBSCO, MEDLINE, and PubMed databases with the following terms: psychiatry, mental health, racism, substance use, suicide, trauma-informed care, disparities and recovery-oriented care. Articles were further filtered based on meeting the criteria of peer-reviewed, full-text availability, written in English, and published between 2018 and 2023. Findings Black patients are more likely to be diagnosed with psychotic disorders and prescribed antipsychotic medications compared to White patients who were more often diagnosed with mood disorders and prescribed antidepressants. This same disparity is also seen in children and adolescents, where Black children are more likely to be diagnosed with behavior problems such as Oppositional Defiant Disorder (ODD) and White children with the same presentation are more likely to be diagnosed with Attention Hyperactivity Disorder. Medications advertisements for antipsychotics like Haldol as recent as 1974 portrayed a Black man, labeled as “agitated” and “aggressive”, a trope we still see today in police violence cases. The majority of nursing and medical school programs do not provide education on racism and how to actively combat it in practice, leaving many healthcare professionals acutely uneducated and unaware of their own biases and racism, as well as structural and institutional racism. Conclusions Racism will continue to grow wherever it is given time, space, and energy. Providers and nurses have an ethical obligation to educate themselves, actively deconstruct their personal racism and bias, and continuously engage in active antiracism by dismantling racism wherever it is encountered, be it structural, institutional, or scientific racism. Agents of change at the patient care level not only improve the outcomes of Black patients, but it will also lead the way in ensuring Black, Indigenous, and other People of Color are included in research of methods and medications in psychiatry in the future.

Keywords: disparities, psychiatry, racism, recovery-oriented care, trauma-informed care

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Authors: Adam J. Bowen

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Abstract— Should robots have rights or legal protections. Often debates concerning whether robots and AI should be afforded rights focus on conditions of personhood and the possibility of future advanced forms of AI satisfying particular intrinsic cognitive and moral attributes of rights-holding persons. Such discussions raise compelling questions about machine consciousness, autonomy, and value alignment with human interests. Although these are important theoretical concerns, especially from a future design perspective, they provide limited guidance for addressing the moral and legal standing of current and near-term AI that operate well below the cognitive and moral agency of human persons. Robots and AI are already being pressed into service in a wide range of roles, especially in healthcare and biomedical contexts. The design and large-scale implementation of robots in the context of core societal institutions like healthcare systems continues to rapidly develop. For example, we bring them into our homes, hospitals, and other care facilities to assist in care for the sick, disabled, elderly, children, or otherwise vulnerable persons. We enlist surgical robotic systems in precision tasks, albeit still human-in-the-loop technology controlled by surgeons. We also entrust them with social roles involving companionship and even assisting in intimate caregiving tasks (e.g., bathing, feeding, turning, medicine administration, monitoring, transporting). There have been advances to enable severely disabled persons to use robots to feed themselves or pilot robot avatars to work in service industries. As the applications for near-term AI increase and the roles of robots in restructuring our biomedical practices expand, we face pressing questions about the normative implications of human-robot interactions and collaborations in our collective worldmaking, as well as the moral and legal status of robots. This paper argues that robots operating in public and private spaces be afforded some protections as either moral patients or legal agents to establish prohibitions on robot abuse, misuse, and mistreatment. We already implement robots and embed them in our practices and institutions, which generates a host of human-to-machine and machine-to-machine relationships. As we interact with machines, whether in service contexts, medical assistance, or home health companions, these robots are first encountered in relationship to us and our respective roles in the encounter (e.g., surgeon, physical or occupational therapist, recipient of care, patient’s family, healthcare professional, stakeholder). This proposal aims to outline a framework for establishing limiting factors and determining the extent of moral or legal protections for robots. In doing so, it advocates for a relational approach that emphasizes the priority of mapping the complex contextually sensitive roles played and the relations in which humans and robots stand to guide policy determinations by relevant institutions and authorities. The relational approach must also be technically informed by the intended uses of the biomedical technologies in question, Design History Files, extensive risk assessments and hazard analyses, as well as use case social impact assessments.

Keywords: biomedical robots, robot ethics, robot laws, human-robot interaction

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Authors: Roland F. Karthaus, Rachel S. O'Brien

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Over the past decade, the authors have undertaken applied research aimed at enabling transformation within the prison service to improve conditions and outcomes for those living, working and visiting in prisons in the UK and the communities they serve. The research has taken place against a context of reducing resources and public discontent at increasing levels of violence, deteriorating conditions and persistently high levels of re-offending. Top-down governmental policies have mainly been ineffectual and in some cases counter-productive. The prison service is characterised by hierarchical organisation, and the research has applied design thinking at multiple levels to challenge and precipitate change: top-down, middle-out and bottom-up. The research employs three distinct but related approaches, system design (top-down): working at the national policy level to analyse the changing policy context, identifying opportunities and challenges; engaging with the Ministry of Justice commissioners and sector organisations to facilitate debate, introducing new evidence and provoking creative thinking, place-based design (middle-out): working with individual prison establishments as pilots to illustrate and test the potential for local empowerment, creative change, and improved architecture within place-specific contexts and organisational hierarchies, everyday design (bottom-up): working with individuals in the system to explore the potential for localised, significant, demonstrator changes; including collaborative design, capacity building and empowerment in skills, employment, communication, training, and other activities. The research spans a series of projects, through which the methodological approach has developed responsively. The projects include a place-based model for the re-purposing of Ministry of Justice land assets for the purposes of rehabilitation; an evidence-based guide to improve prison design for health and well-being; capacity-based employment, skills and self-build project as a template for future open prisons. The overarching research has enabled knowledge to be developed and disseminated through policy and academic networks. Whilst the research remains live and continuing; key findings are emerging as a basis for a new methodological approach to effecting change in the UK prison service. An interdisciplinary approach is necessary to overcome the barriers between distinct areas of the prison service. Sometimes referred to as total environments, prisons encompass entire social and physical environments which themselves are orchestrated by institutional arms of government, resulting in complex systems that cannot be meaningfully engaged through narrow disciplinary lenses. A scalar approach is necessary to connect strategic policies with individual experiences and potential, through the medium of individual prison establishments, operating as discrete entities within the system. A reflexive process is necessary to connect research with action in a responsive mode, learning to adapt as the system itself is changing. The role of individuals in the system, their latent knowledge and experience and their ability to engage and become agents of change are essential. Whilst the specific characteristics of the UK prison system are unique, the approach is internationally applicable.

Keywords: architecture, design, policy, prison, system, transformation

Procedia PDF Downloads 102

Authors: Mohammed S. Razali, Kamel Khimeche, Dahah Hichem, Ammar Boudjellal, Djamel E. Kaderi, Nourddine Ramdani

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The use of additive manufacturing technologies has revolutionized various aspects of our daily lives. In particular, 3D printing has greatly advanced biomedical applications. While fused filament fabrication (FFF) technologies have made it easy to produce or prototype various medical devices, it is crucial to minimize the risk of contamination. New materials with antibacterial properties, such as those containing compounded silver nanoparticles, have emerged on the market. In a previous study, we prepared a newly sintered seashell filler (SSh) from bio-based seashells found along the Mediterranean coast using a suitable heat treatment process. We then prepared a series of polylactic acid (PLA) and polybutylene succinate (PBS) biocomposites filled with these SSh particles using a melt mixing technique with a twin-screw extruder to use them as feedstock filaments for 3D printing. The study consisted of two parts: evaluating the antibacterial activity of newly prepared biocomposites made of PLA and PBS reinforced with a sintered seashell in the first part and experimental and modeling analysis of the non-isothermal crystallization kinetics of these biocomposites in the second part. In the first part, the bactericidal activity of the biocomposites against three different bacteria, including Gram-negative bacteria such as (E. coli and Pseudomonas aeruginosa), as well as Gram-positive bacteria such as (Staphylococcus aureus), was examined. The PLA-based biocomposite containing 20 wt.% of SSh particles exhibited an inhibition zone with radial diameters of 8mm and 6mm against E. coli and Pseudo. Au, respectively, while no bacterial activity was observed against Staphylococcus aureus. In the second part, the focus was on investigating the effect of the sintered seashell filler particles on the non-isothermal crystallization kinetics of PLA and PBS 3D-printing composite materials. The objective was to understand the impact of the filler particles on the crystallization mechanism of both PLA and PBS during the cooling process of a melt-extruded filament in (FFF) to manage the dimensional accuracy and mechanical properties of the final printed part. We conducted a non-isothermal melt crystallization kinetic study of a series of PLA-SS and PBS-SS composites using differential scanning calorimetry at various cooling rates. We analyzed the obtained kinetic data using different crystallization kinetic models such as modified Avrami, Ozawa, and Mo's methods. Dynamic mode describes the relative crystallinity as a function of temperature; it found that time half crystallinity (t1/2) of neat PLA decreased from 17 min to 7.3 min for PLA+5 SSh and the (t1/2) of virgin PBS was reduced from 3.5 min to 2.8 min for the composite containing 5wt.% of SSh. We found that the coated SS particles with stearic acid acted as nucleating agents and had a nucleation activity, as observed through polarized optical microscopy. Moreover, we evaluated the effective energy barrier of the non-isothermal crystallization process using the Iso conversional methods of Flynn-Wall-Ozawa (F-W-O) and Kissinger-Akahira-Sunose (K-A-S). The study provides significant insights into the crystallization behavior of PLA and PBS biocomposites.

Keywords: avrami model, bio-based reinforcement, dsc, gram-negative bacteria, gram-positive bacteria, isoconversional methods, non-isothermal crystallization kinetics, poly(butylene succinate), poly(lactic acid), antbactirial activity

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Authors: Alison C. Essary, Victor Trastek

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Introduction: The current state of the health care system in the U.S. is characterized by an unprecedented number of people living with multiple chronic conditions, unsustainable rise in health care costs, inadequate access to care, and wide variation in health outcomes throughout the country. An estimated two-thirds of Americans are living with two or more chronic conditions, contributing to 75% of all health care spending. In 2013, the School for the Science of Health Care Delivery (SHCD) was charged with redesigning the health care system through education and research. Faculty in business, law, and public policy, and thought leaders in health care delivery, administration, public health and health IT created undergraduate, graduate, and executive academic programs to address this pressing need. Faculty and students work across disciplines, and with community partners and employers to improve care delivery and increase value for patients. Methods: Curricula apply content in health care administration and operations within the clinical context. Graduate modules are team-taught by faculty across academic units to model team-based practice. Seminars, team-based assignments, faculty mentoring, and applied projects are integral to student success. Cohort-driven models enhance networking and collaboration. This observational study evaluated two years of admissions data, and one year of graduate data to assess program outcomes and inform the current graduate-level curricula. Descriptive statistics includes means, percentages. Results: Fall 2013, the program received 51 applications. The mean GPA of the entering class of 37 students was 3.38. Ninety-seven percent of the fall 2013 cohort successfully completed the program (n=35). Sixty-six percent are currently employed in the health care industry (n=23). Of the remaining 12 graduates, two successfully matriculated to medical school; one works in the original field of study; four await results on the MCAT or DAT, and five were lost to follow up. Attrition of one student was attributed to non-academic reasons. Fall 2014, the program expanded to include both on-ground and online cohorts. Applications were evenly distributed between on-ground (n=70) and online (n=68). Thirty-eight students enrolled in the on-ground program. The mean GPA was 3.95. Ninety-five percent of students successfully completed the program (n=36). Thirty-six students enrolled in the online program. The mean GPA was 3.85. Graduate outcomes are pending. Discussion: Challenges include demographic variability between online and on-ground students; yet, both profiles are similar in that students intend to become change agents in the health care system. In the past two years, on-ground applications increased by 31%, persistence to graduation is > 95%, mean GPA is 3.67, graduates report admission to six U.S. medical schools, the Mayo Medical School integrates SHCD content within their curricula, and there is national interest in collaborating on industry and academic partnerships. This places SHCD at the forefront of developing innovative curricula in order to improve high-value, patient-centered care.

Keywords: delivery science, education, health care delivery, high-value care, innovation in education, patient-centered

Procedia PDF Downloads 255

Authors: Marcial Blondet, Malena Serrano, Álvaro Rubiños, Elin Mattsson

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In Peru, there are more than two million houses made of adobe (sun dried mud bricks) or rammed earth (35% of the total houses), in which almost 9 million people live, mainly because they cannot afford to purchase industrialized construction materials. Although adobe houses are cheap to build and thermally comfortable, their seismic performance is very poor, and they usually suffer significant damage or collapse with tragic loss of life. Therefore, over the years, researchers at the Pontifical Catholic University of Peru and other institutions have developed many reinforcement techniques as an effort to improve the structural safety of earthen houses located in seismic areas. However, most rural communities live under unacceptable seismic risk conditions because these techniques have not been adopted massively, mainly due to high cost and lack of diffusion. The nylon rope mesh reinforcement technique is simple and low-cost, and two technological transference tools have been developed to diffuse it among rural communities: 1) Scale seismic simulations using a portable shaking table have been designed to prove its effectiveness to protect adobe houses; 2) A step-by-step illustrated construction manual has been developed to guide the complete building process of a nylon rope mesh reinforced adobe house. As a study case, it was selected the district of Pullo: a small rural community in the Peruvian Andes where more than 80% of its inhabitants live in adobe houses and more than 60% are considered to live in poverty or extreme poverty conditions. The research team carried out a one-day workshop in May 2015 and a two-day workshop in September 2015. Results were positive: First, the nylon rope mesh reinforcement procedure was proven simple enough to be replicated by adults, both young and seniors, and participants handled ropes and knots easily as they use them for daily livestock activity. In addition, nylon ropes were proven highly available in the study area as they were found at two local stores in variety of color and size.. Second, the portable shaking table demonstration successfully showed the effectiveness of the nylon rope mesh reinforcement and generated interest on learning about it. On the first workshop, more than 70% of the participants were willing to formally subscribe and sign up for practical training lessons. On the second workshop, more than 80% of the participants returned the second day to receive introductory practical training. Third, community members found illustrations on the construction manual simple and friendly but the roof system illustrations led to misinterpretation so they were improved. The technological transfer tools developed in this project can be used to train rural dwellers on earthquake-resistant self-construction with adobe, which is still very common in the Peruvian Andes. This approach would allow community members to develop skills and capacities to improve safety of their households on their own, thus, mitigating their high seismic risk and preventing tragic losses. Furthermore, proper training in earthquake-resistant self-construction with adobe would prevent rural dwellers from depending on external aid after an earthquake and become agents of their own development.

Keywords: adobe, Peruvian Andes, safe housing, technological transference

Procedia PDF Downloads 266

Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

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Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

Procedia PDF Downloads 147

Authors: Mohammad Shajid Rahman, Tarik Kaya, Edgar Matida

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Electronic cigarettes, also known as e-cigarettes, may have become a tool to improve smoking cessation due to their ability to provide nicotine at a selected rate. Unlike traditional cigarettes, which produce toxic elements from tobacco combustion, e-cigarettes generate aerosols by heating a liquid solution (commonly a mixture of propylene glycol, vegetable glycerin, nicotine and some flavoring agents). However, caution still needs to be taken when using e-cigarettes due to the presence of addictive nicotine and some harmful substances produced from the heating process. Particle size distribution (PSD) and associated velocities generated by e-cigarettes have significant influence on aerosol deposition in different regions of human respiratory tracts. On another note, low actuation power is beneficial in aerosol generating devices since it exhibits a reduced emission of toxic chemicals. In case of e-cigarettes, lower heating powers can be considered as powers lower than 10 W compared to a wide range of powers (0.6 to 70.0 W) studied in literature. Due to the importance regarding inhalation risk reduction, deeper understanding of particle size characteristics of e-cigarettes demands thorough investigation. However, comprehensive study on PSD and velocities of e-cigarettes with a standard testing condition at relatively low heating powers is still lacking. The present study aims to measure particle number count and size distribution of undiluted aerosols of a latest fourth-generation e-cigarette at low powers, within 6.5 W using real-time particle counter (time-of-flight method). Also, temporal and spatial evolution of particle size and velocity distribution of aerosol jets are examined using phase Doppler anemometry (PDA) technique. To the authors’ best knowledge, application of PDA in e-cigarette aerosol measurement is rarely reported. In the present study, preliminary results about particle number count of undiluted aerosols measured by time-of-flight method depicted that an increase of heating power from 3.5 W to 6.5 W resulted in an enhanced asymmetricity in PSD, deviating from log-normal distribution. This can be considered as an artifact of rapid vaporization, condensation and coagulation processes on aerosols caused by higher heating power. A novel mathematical expression, combining exponential, Gaussian and polynomial (EGP) distributions, was proposed to describe asymmetric PSD successfully. The value of count median aerodynamic diameter and geometric standard deviation laid within a range of about 0.67 μm to 0.73 μm, and 1.32 to 1.43, respectively while the power varied from 3.5 W to 6.5 W. Laser Doppler velocimetry (LDV) and PDA measurement suggested a typical centerline streamwise mean velocity decay of aerosol jet along with a reduction of particle sizes. In the final submission, a thorough literature review, detailed description of experimental procedure and discussion of the results will be provided. Particle size and turbulent characteristics of aerosol jets will be further examined, analyzing arithmetic mean diameter, volumetric mean diameter, volume-based mean diameter, streamwise mean velocity and turbulence intensity. The present study has potential implications in PSD simulation and validation of aerosol dosimetry model, leading to improving related aerosol generating devices.

Keywords: E-cigarette aerosol, laser doppler velocimetry, particle size distribution, particle velocity, phase Doppler anemometry

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Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

Procedia PDF Downloads 237

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

Procedia PDF Downloads 90

Authors: Zeyu Zhou, Ziyu Zhao, Xiaochen Yang, Ling AI, Heng Zhai, Stuart Holmes

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As a promising sustainable alternative to traditional fossil fuels, fuel cell technology is highly favoured due to its enhanced working efficiency and reduced emissions. In the context of high-temperature fuel cells (operating above 100 °C), the most commonly used proton exchange membrane (PEM) is the Polybenzimidazole (PBI) doped phosphoric acid (PA) membrane. Grafting is a promising strategy to advance PA-doped PBI PEM technology. The existing grafting modification on PBI PEMs mainly focuses on grafting phosphate-containing or alkaline groups onto the PBI molecular chains. However, quaternary ammonium-based grafting approaches face a common challenge. To initiate the N-alkylation reaction, deacidifying agents such as NaH, NaOH, KOH, K2CO3, etc., can lead to ionic crosslinking between the quaternary ammonium group and PBI. Polyvinylpyrrolidone (PVP) is another widely used polymer, the N-heterocycle groups within PVP endow it with a significant ability to absorb PA. Recently, PVP has attracted substantial attention in the field of fuel cells due to its reduced environmental impact and impressive fuel cell performance. However, due to the the poor compatibility of PVP in PBI, few research apply PVP in PA-doped PBI PEMs. This work introduces an innovative strategy to graft PVP onto PBI to form a network-like polymer. Due to the absence of quaternary ammonium groups, PVP does not pose issues related to crosslinking with PBI. Moreover, the nitrogen-containing functional groups on PVP provide PBI with a robust phosphoric acid retention ability. The nuclear magnetic resonance (NMR) hydrogen spectrum analysis results indicate the successful completion of the grafting reaction where N-alkylation reactions happen on both sides of the grafting agent 1,4-bis(chloromethyl)benzene. On one side, the reaction takes place with the hydrogen atoms on the imidazole groups of PBI, while on the other side, it reacts with the terminal amino group of PVP. The XPS results provide additional evidence from the perspective of the element. On synthesized PBI-g-PVP surfaces, there is an absence of chlorine (chlorine in grafting agent 1,4-bis(chloromethyl)benzene is substituted) element but a presence of sulfur element (sulfur element in terminal amino PVP appears in PBI), which demonstrates the occurrence of the grafting reaction and PVP is successfully grafted onto PBI. Prepare these modified membranes into MEA. It was found that during the fuel cell operation, all the grafted membranes showed substantial improvement in maximum current density and peak power density compared to unmodified one. For PBI-g-PVP 30, with a grafting degree of 22.4%, the peak power density reaches 1312 mW cm⁻², marking a 59.6% enhancement compared to the pristine PBI membrane. The improvement is caused by the improved PA binding ability of the membrane after grafting. The AST test result shows that the grafting membranes have better long-term durability and performance than unmodified membranes attributed to the presence of added PA binding sites, which can effectively prevent the PA leaching caused by proton migration. In conclusion, the test results indicate that grafting PVP onto PBI is a promising strategy which can effectively improve the fuel cell performance.

Keywords: fuel cell, grafting modification, PA doping ability, PVP

Procedia PDF Downloads 35

Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

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Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

Procedia PDF Downloads 286

Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

Procedia PDF Downloads 241

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Tianfang Zhang, Luxi He, Zhengbin He, Songlin Yi

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Moso bamboo is a common non-wood forest resource in Asia that is widely used in construction, furniture, and other fields. Influenced by the heterogeneous structure and various hygroscopic groups of bamboo, the deformation occurs as moisture absorption and desorption when the environment temperature and humidity conditions change. Thermal modification is a well-established commercial technology for improving the dimensional stability of bamboo. However, the higher energy consumption and carbon emissions limit its further development. Previous studies have indicated that inorganic salt-assisted thermal modification could lead to significant reductions in moisture absorption and energy consumption. Represented by metal chlorides, it could show Lewis acid properties when dissolved in water, generating metal ion ligand complexes. In addition, ultrasonic treatment, as an efficient and environmentally friendly physical treatment method, improved the accessibility of pretreatment chemical impregnation agents and intensified mass and heat transfer during reactions. To save energy and reduce deformation, this study elucidates the influence of zinc chloride-ultrasonic treatment on the physicochemical properties of heat-treated bamboo, and the details of the bamboo deformation mechanism with Lewis acid are explained. Three sets of parameters (inorganic salt concentration, ultrasonic frequency and heat treatment temperature) were designed, and an optimized process was proposed to clarify this scientific question, that is: 5% (w/w) zinc chloride solution, 40 kHz ultrasonic waves and heat treatment at 160 °C. The samples were characterized by different means to analyze changes in their macroscopic features, pore structure, chemical structure and chemical composition. The results suggested that the maximum weight loss rate was reduced by at least 19.75%. The maximum thermal degradation peak of hemicellulose was significantly shifted forward. The hygroscopicity was reduced by 10.15%, the relative crystallinity was increased by 4.4%, the surface contact angle was increased by 25.2%, and the color change was increased by 23.60 in the optimal condition. From the electron microscope observation, the treated surface became rougher, and cracks appeared in some weaker areas, accelerating starch loss and removing granular attachments around the pits. By ion diffusion, zinc ions diffused into hemicellulose and a partial amorphous region of cellulose. Parts of the cell wall structure were subjected to swelling and degradation, leading to the broken state of parenchyma cells. From the Raman spectrum, compared to conventional thermal modifications, hemicellulose thermal degradation and lignin migration is promoted by Lewis acid under dilute acid-thermal condition. As shown in this work, the combined Lewis acid and ultrasonic pretreatment as an environmentally friendly, safe, and efficient physic-chemical combined pretreatment method improved the dimensional stability of Moso bamboo and lowered the thermal degradation conditions. This method has great potential for development in the field of bamboo heat treatment, and it might provide some guidance for making dark bamboo flooring.

Keywords: Moso bamboo, Lewis acid, ultrasound, heat treatment

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Authors: Bidzina Matsaberidze, Anna Sikharulidze, Gia Sirbiladze, Bezhan Ghvaberidze

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In the modern world emergency management decision support systems are actively used by state organizations, which are interested in extreme and abnormal processes and provide optimal and safe management of supply needed for the civil and military facilities in geographical areas, affected by disasters, earthquakes, fires and other accidents, weapons of mass destruction, terrorist attacks, etc. Obviously, these kinds of extreme events cause significant losses and damages to the infrastructure. In such cases, usage of intelligent support technologies is very important for quick and optimal location-transportation of emergency service in order to avoid new losses caused by these events. Timely servicing from emergency service centers to the affected disaster regions (response phase) is a key task of the emergency management system. Scientific research of this field takes the important place in decision-making problems. Our goal was to create an expert knowledge-based intelligent support system, which will serve as an assistant tool to provide optimal solutions for the above-mentioned problem. The inputs to the mathematical model of the system are objective data, as well as expert evaluations. The outputs of the system are solutions for Fuzzy Multi-Objective Emergency Location-Transportation Problem (FMOELTP) for disasters’ regions. The development and testing of the Intelligent Support System were done on the example of an experimental disaster region (for some geographical zone of Georgia) which was generated using a simulation modeling. Four objectives are considered in our model. The first objective is to minimize an expectation of total transportation duration of needed products. The second objective is to minimize the total selection unreliability index of opened humanitarian aid distribution centers (HADCs). The third objective minimizes the number of agents needed to operate the opened HADCs. The fourth objective minimizes the non-covered demand for all demand points. Possibility chance constraints and objective constraints were constructed based on objective-subjective data. The FMOELTP was constructed in a static and fuzzy environment since the decisions to be made are taken immediately after the disaster (during few hours) with the information available at that moment. It is assumed that the requests for products are estimated by homeland security organizations, or their experts, based upon their experience and their evaluation of the disaster’s seriousness. Estimated transportation times are considered to take into account routing access difficulty of the region and the infrastructure conditions. We propose an epsilon-constraint method for finding the exact solutions for the problem. It is proved that this approach generates the exact Pareto front of the multi-objective location-transportation problem addressed. Sometimes for large dimensions of the problem, the exact method requires long computing times. Thus, we propose an approximate method that imposes a number of stopping criteria on the exact method. For large dimensions of the FMOELTP the Estimation of Distribution Algorithm’s (EDA) approach is developed.

Keywords: epsilon-constraint method, estimation of distribution algorithm, fuzzy multi-objective combinatorial programming problem, fuzzy multi-objective emergency location/transportation problem

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Authors: Muhammed Jamiu Mustapha, Jamiu Folarin, Stephen Obiri Agyei, Rasheed Ademola Adebiyi, Mutiu Iyanda Lasisi

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The role of information in societal development and growth cannot be over-emphasized. It has remained an age-long strategy to adopt the information flow to make an egalitarian society. The same has become a tool for throwing society into chaos and anarchy. It has been adopted as a weapon of war and a veritable instrument of psychological warfare with a variety of uses. That is why some scholars posit that information could be deployed as a weapon to wreak “Mass Destruction" or promote “Mass Development". When used as a tool for destruction, the effect on society is like an atomic bomb which when it is released, pollutes the air and suffocates the people. Technological advancement has further exposed the latent power of information and many societies seem to be overwhelmed by its negative effect. While information remains one of the bedrock of democracy, the information ecosystem across the world is currently facing a more difficult battle than ever before due to information pluralism and technological advancement. The more the agents involved try to combat its menace, the difficult and complex it is proving to be curbed. In a region like Africa with dangling democracy enfolds with complexities of multi-religion, multi-cultures, inter-tribes, ongoing issues that are yet to be resolved, it is important to pay critical attention to the case of information disorder and find appropriate ways to curb or mitigate its effects. The media, being the middleman in the distribution of information, needs to build capacities and capabilities to separate the whiff of misinformation and disinformation from the grains of truthful data. From quasi-statistical senses, it has been observed that the efforts aimed at fighting information pollution have not considered the built resilience of media organisations against this disorder. Apparently, the efforts, resources and technologies adopted for the conception, production and spread of information pollution are much more sophisticated than approaches to suppress and even reduce its effects on society. Thus, this study seeks to interrogate the phenomenon of information pollution and the capabilities of select media organisations in Sub-Saharan Africa. In doing this, the following questions are probed; what are the media actions to curb the menace of information pollution? Which of these actions are working and how effective are they? And which of the actions are not working and why they are not working? Adopting quantitative and qualitative approaches and anchored on the Dynamic Capability Theory, the study aims at digging up insights to further understand the complexities of information pollution, media capabilities and strategic resources for managing misinformation and disinformation in the region. The quantitative approach involves surveys and the use of questionnaires to get data from journalists on their understanding of misinformation/disinformation and their capabilities to gate-keep. Case Analysis of select media and content analysis of their strategic resources to manage misinformation and disinformation is adopted in the study while the qualitative approach will involve an In-depth Interview to have a more robust analysis is also considered. The study is critical in the fight against information pollution for a number of reasons. One, it is a novel attempt to document the level of media capabilities to fight the phenomenon of information disorder. Two, the study will enable the region to have a clear understanding of the capabilities of existing media organizations to combat misinformation and disinformation in the countries that make up the region. Recommendations emanating from the study could be used to initiate, intensify or review existing approaches to combat the menace of information pollution in the region.

Keywords: disinformation, information pollution, misinformation, media capabilities, sub-Saharan Africa

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Authors: Martin Cvek, Miroslav Mrlik, Michal Sedlacik, Tomas Plachy

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Magnetorheological elastomers (MREs) are multi-phase composite materials containing micron-sized ferromagnetic particles dispersed in an elastomeric matrix. Their properties such as modulus, damping, magneto-striction, and electrical conductivity can be controlled by an external magnetic field and/or pressure. These features of the MREs are used in the development of damping devices, shock attenuators, artificial muscles, sensors or active elements of electric circuits. However, imperfections on the particle/matrix interfaces result in the lower performance of the MREs when compared with theoretical values. Moreover, magnetic particles are susceptible to corrosion agents such as acid rains or sea humidity. Therefore, the modification of particles is an effective tool for the improvement of MRE performance due to enhanced compatibility between particles and matrix as well as improvements of their thermo-oxidation and chemical stability. In this study, the carbonyl iron (CI) particles were controllably modified with poly(trimethylsilyloxyethyl methacrylate) (PHEMATMS) nano-grafts to develop magnetic core–shell structures exhibiting proper wetting with various elastomeric matrices resulting in improved performance within a frame of rheological, magneto-piezoresistance, pressure-piezoresistance, or radio-absorbing properties. The desired molecular weight of PHEMATMS nano-grafts was precisely tailored using surface-initiated atom transfer radical polymerization (ATRP). The CI particles were firstly functionalized using a 3-aminopropyltriethoxysilane agent, followed by esterification reaction with α-bromoisobutyryl bromide. The ATRP was performed in the anisole medium using ethyl α-bromoisobutyrate as a macroinitiator, N, N´, N´´, N´´-pentamethyldiethylenetriamine as a ligand, and copper bromide as an initiator. To explore the effect PHEMATMS molecular weights on final properties, two variants of core-shell structures with different nano-graft lengths were synthesized, while the reaction kinetics were designed through proper reactant feed ratios and polymerization times. The PHEMATMS nano-grafts were characterized by nuclear magnetic resonance and gel permeation chromatography proving information to their monomer conversions, molecular chain lengths, and low polydispersity indexes (1.28 and 1.35) as the results of the executed ATRP. The successful modifications were confirmed via Fourier transform infrared- and energy-dispersive spectroscopies while expected wavenumber outputs and element presences, respectively, of constituted PHEMATMS nano-grafts, were occurring in the spectra. The surface morphology of bare CI and their PHEMATMS-grafted analogues was further studied by scanning electron microscopy, and the thicknesses of grafted polymeric layers were directly observed by transmission electron microscopy. The contact angles as a measure of particle/matrix compatibility were investigated employing the static sessile drop method. The PHEMATMS nano-grafts enhanced compatibility of hydrophilic CI with low-surface-energy hydrophobic polymer matrix in terms of their wettability and dispersibility in an elastomeric matrix. Thus, the presence of possible defects at the particle/matrix interface is reduced, and higher performance of modified MREs is expected.

Keywords: atom transfer radical polymerization, core-shell, particle modification, wettability

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Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

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Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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Authors: Elena Parmentier, Henrik Endeman

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Introduction: Large mediastinal masses often present with diagnostic and clinical challenges due to compression of the respiratory and hemodynamic system. We present a case of a mediastinal mass with symptomatic mechanical compression of the trachea, resulting in challenging airway management. Methods: We present a case of 66-year-old male, complaining of progressive dysphagia. Initial esophagogastroscopy revealed a stenosis secondary to external compression, biopsies were inconclusive. Additional CT scan showed a large mediastinal mass of unknown origin, situated between the vertebrae and esophagus. Symptoms progressed and patient developed dyspnea and stridor. A new CT showed quick growth of the mass with compression of the trachea, subglottic to just above the carina. A tracheal covered stent was successfully placed. Endobronchial ultrasound revealed a large irregular mass without tracheal invasion, biopsies were taken. 4 days after stent placement, the patients’ condition deteriorated with worsening of stridor, dyspnea and desaturation. Migration of the tracheal stent into the right main bronchus was seen on chest X ray, with obstruction of the left main bronchus and secondary atelectasis. Different methods have been described in the literature for tracheobronchial stent removal (surgical, endoscopic, fluoroscopyguided), our first choice in this case was flexible bronchoscopy. However, this revealed tracheal compression above the migrated stent and passage of the scope occurred impossible. Patient was admitted to the ICU, high-flow nasal oxygen therapy was started and the situation stabilized, giving time for extensive assessment and preparation of the airway management approach. Close cooperation between the intensivist, pulmonologist, anesthesiologist and otorhinolaryngologist was essential. Results: In case of sudden deterioration, a protocol for emergency situations was made. Given the increased risk of additional tracheal compression after administration of neuromuscular blocking agents, an approach with awake fiberoptic intubation maintaining spontaneous ventilation was proposed. However, intubation without retrieval of the tracheal stent was found undesirable due to expected massive shunting over the left atelectatic lung. As rescue option, assistance of extracorporeal circulation was considered and perfusionist was kept on standby. The patient stayed stable and was transferred to the operating theatre. High frequency jet ventilation under general anesthesia resulted in desaturations up to 50%, making rigid bronchoscopy impossible. Subsequently an endotracheal tube size 8 could be placed successfully and the stent could be retrieved via bronchoscopy over (and with) the tube, after which the patient was reintubated. Finally, a tracheostomy (Shiley™ Tracheostomy Tube With Cuff, size 8) was placed, fiberoptic control showed a patent airway. Patient was readmitted to the ICU and could be quickly weaned of the ventilator. Pathology was positive for rhabdomyosarcoma, without indication for systemic therapy. Extensive surgery (laryngectomy, esophagectomy) was suggested, but patient refused and palliative care was started. Conclusion: Due to meticulous planning in an interdisciplinary team, we showed a successful airway management approach in this complicated case of critical airway compression secondary to a rare rhabdomyosarcoma, complicated by tracheal stent migration. Besides presenting our thoughts and considerations, we support exploring other possible approaches of this specific clinical problem.

Keywords: airway management, rhabdomyosarcoma, stent displacement, tracheal stenosis

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