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Authors: Marielle Leijten, Catherine Meulemans, Sven De Maeyer, Luuk Van Waes

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For the diagnosis of Alzheimer's disease (AD), a large variety of neuropsychological tests are available. In some of these tests, linguistic processing - both oral and written - is an important factor. Language disturbances might serve as a strong indicator for an underlying neurodegenerative disorder like AD. However, the current diagnostic instruments for language assessment mainly focus on product measures, such as text length or number of errors, ignoring the importance of the process that leads to written or spoken language production. In this study, it is our aim to describe and test differences between cognitive and impaired elderly on the basis of a selection of writing process variables (inter- and intrapersonal characteristics). These process variables are mainly related to pause times, because the number, length, and location of pauses have proven to be an important indicator of the cognitive complexity of a process. Method: Participants that were enrolled in our research were chosen on the basis of a number of basic criteria necessary to collect reliable writing process data. Furthermore, we opted to match the thirteen cognitively impaired patients (8 MCI and 5 AD) with thirteen cognitively healthy elderly. At the start of the experiment, participants were each given a number of tests, such as the Mini-Mental State Examination test (MMSE), the Geriatric Depression Scale (GDS), the forward and backward digit span and the Edinburgh Handedness Inventory (EHI). Also, a questionnaire was used to collect socio-demographic information (age, gender, eduction) of the subjects as well as more details on their level of computer literacy. The tests and questionnaire were followed by two typing tasks and two picture description tasks. For the typing tasks participants had to copy (type) characters, words and sentences from a screen, whereas the picture description tasks each consisted of an image they had to describe in a few sentences. Both the typing and the picture description tasks were logged with Inputlog, a keystroke logging tool that allows us to log and time stamp keystroke activity to reconstruct and describe text production processes. The main rationale behind keystroke logging is that writing fluency and flow reveal traces of the underlying cognitive processes. This explains the analytical focus on pause (length, number, distribution, location, etc.) and revision (number, type, operation, embeddedness, location, etc.) characteristics. As in speech, pause times are seen as indexical of cognitive effort. Results. Preliminary analysis already showed some promising results concerning pause times before, within and after words. For all variables, mixed effects models were used that included participants as a random effect and MMSE scores, GDS scores and word categories (such as determiners and nouns) as a fixed effect. For pause times before and after words cognitively impaired patients paused longer than healthy elderly. These variables did not show an interaction effect between the group participants (cognitively impaired or healthy elderly) belonged to and word categories. However, pause times within words did show an interaction effect, which indicates pause times within certain word categories differ significantly between patients and healthy elderly.

Keywords: Alzheimer's disease, keystroke logging, matching, writing process

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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: Justine Salam

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As a federal state, Canada’s constitutional arrangements regarding the management of natural resources is unique because it gives complete ownership and control of natural resources to the provinces (subnational level). However, the province of Alberta—home to the third largest oil reserves in the world—lags behind comparable jurisdictions in levying royalties on oil corporations, especially oil sands royalties. While Albertans own the oil sands, scholars have argued that natural resource exploitation in Alberta benefits corporations and industry more than it does Albertans. This study provides a systematic understanding of the causal factors affecting royalties in Alberta to map dynamics of power and how they manifest themselves during policy-making. Mounting domestic and global public pressure led Alberta to review its oil sands royalties twice in less than a decade through public-commissioned Royalty Review Panels, first in 2007 and again in 2015. The Panels’ task was to research best practices and to provide policy recommendations to the Government through public consultations with Albertans, industry, non-governmental organizations, and First Nations peoples. Both times, the Panels recommended a relative increase to oil sands royalties. However, irrespective of the Reviews’ recommendations, neither the right-wing 2007 Progressive Conservative Party (PC) nor the left-wing 2015 New Democratic Party (NDP) government—both committed to increase oil sands royalties—increased royalty intake. Why did two consecutive political parties at opposite ends of the political spectrum fail to account for the recommendations put forward by the Panel? Through a qualitative case-study analysis, this study assesses domestic and global causal factors for Alberta’s inability to raise oil sands royalties significantly after the two Reviews through an institutions, interests, and ideas framework. Indeed, causal factors can be global (e.g. market and price fluctuation) or domestic (e.g. oil companies’ influence on the Alberta government). The institutions, interests, and ideas framework is at the intersection of public policy, comparative studies, and political economy literatures, and therefore draws multi-faceted insights into the analysis. To account for institutions, the study proposes to review international trade agreements documents such as the North American Free Trade Agreement (NAFTA) because they have embedded Alberta’s oil sands into American energy security policy and tied Canadian and Albertan oil policy in legal international nods. To account for interests, such as how the oil lobby or the environment lobby can penetrate governmental decision-making spheres, the study draws on the Oil Sands Oral History project, a database of interviews from government officials and oil industry leaders at a pivotal time in Alberta’s oil industry, 2011-2013. Finally, to account for ideas, such as how narratives of Canada as a global ‘energy superpower’ and the importance of ‘energy security’ have dominated and polarized public discourse, the study relies on content analysis of Alberta-based pro-industry newspapers to trace the prevalence of these narratives. By mapping systematically the nods and dynamics of power at play in Alberta, the study sheds light on the factors that influence royalty policy-making in one of the largest industries in Canada.

Keywords: Alberta Canada, natural resources governance, oil sands, political economy

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Authors: Ivana Cabarkapa, Zorica Tomicic, Olivera Duragic

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Antimicrobial resistance represents one of the major challenges facing humanity in the last decades. Increasing antibiotic-resistant pathogens indicates the need for the development of alternative antibacterial drugs and new treatment strategies. One of the innovative emerging treatments in overcoming multidrug-resistant pathogens certainly represents the inhibition anti-quorum sensing system. For most of the food-borne pathogens, the expression of the virulence depends on their capability communication with other members of the population by means of quorum sensing (QS). QS represents a specific way of bacterial intercellular communication, which enabled owing to their ability to detect and to respond to cell population density by gene regulation. QS mechanisms are responsible for controls the pathogenesis, virulence luminescence, motility, sporulation and biofilm formation of many organisms by regulating gene expression. Therefore, research in this field is being an attractive target for the development of new natural antibacterial agents. Anti-QS compounds are known to have the ability to prohibit bacterial pathogenicity. Considering the importance of quorum sensing during bacterial pathogenesis, this research has been focused on evaluation anti - QS properties of four essential oils (EOs) Origanum heracleoticum, Origanum vulgare, Thymus vulgare, and Thymus serpyllum, using biomonitor strain of Chromobacterium violaceum CV026. Tests conducted on Luria Bertani agar supplemented with N hexanol DL homoserine lacton (HHL) 10µl/50ml of agar. The anti-QS potential of the EOs was assayed in a range of concentrations of 200 – 0.39 µl/ml using the disc diffusion method. EOs of Th. vulgaris and T. serpyllum were exhibited anti-QS activity indicated by a non- pigmented ring with a dilution-dependent manner. The lowest dilution of EOs T. vulgaris and T. serpyllum in which they exhibited visually detectable inhibition of violacein synthesis was 6.25 µl/ml for both tested EOs. EOs of O. heracleoticum and O. vulgare were displayed different active principles, i.e., antimicrobial activity indicated by the inner clear ring and anti-QS activity indicated by the outer non-pigmented ring, in a concentration-dependent manner. The lowest dilution of EOs of O. heracleoticum and O. vulgare in which exhibited visually detectable inhibition of violacein synthesis was 1.56 and 3.25 µl/ml, respectively. Considering that, the main constituents of the tested EOs represented by monoterpenes (carvacrol, thymol, γ-terpinene, and p-cymene), anti - QS properties of tested EOs can be mainly attributed to their activity. In particular, from the scientific literature, carvacrol and thymol show a sub-inhibitory effect against foodborne pathogens. Previous studies indicated that sub-lethal concentrations of carvacrol reduced the mobility of bacteria due to the ability of interference using QS mechanism between the bacterial cells, and thereby reducing the ability of biofilm formation The precise mechanism by which carvacrol inhibits biofilm formation is still not fully understood. Our results indicated that EOs displayed different active principles, i.e., antimicrobial activity indicated by the inner clear ring and anti-QS activity indicated by an outer non- pigmented ring with visually detectable inhibition of violacein. Preliminary results suggest that EOs represent a promising alternative for effective control of the emergence and spread of resistant pathogens.

Keywords: anti-quorum sensing activity, Chromobacterium violaceum, essential oils, violacein

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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

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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

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Authors: Vijay Samuel, Tina Thekkekkara, Shoma Ganguly

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There is no reported Hanta Seoul virus infection in children in the UK so far, making it quite challenging for clinicians in diagnosing, predicting and prognosticating the outcome of the infection to patients and parents. We report a case of a ten-year-old girl who presented with pyrexia associated with headache, photophobia and abdominal pain. The family had recently acquired two pet rats six weeks ago. She appeared flushed with peri-oral pallor, coated the strawberry tongue, inflamed tonsils and bilateral cervical lymphadenopathy. Her liver and splenic edges were palpable. Investigations showed that she was thrombocytopenic with deranged renal and liver functions. An ultrasound abdomen demonstrated a mildly enlarged spleen, peripancreatic lymph node and an acalculous cholecystitis. In view of her clinical presentation, a diagnosis of leptospirosis was considered and she was commenced on intravenous benzylpenicillin. The following day she became oliguric, developed significant proteinuria and her renal function deteriorated. Following conservative management, her urine output gradually improved along with her renal function, proteinuria and thrombocytopaenia. Serology for leptospirosis and various other viruses were negative. Following discussion with the Rare and Imported Pathogens Laboratory at Porton hanta virus serology was requested and found to be strongly positive for Seoul hanta virus. Following discharge she developed palpitations, fatigue, severe headache and cognitive difficulties including memory loss and difficulties in spelling, reading and mathematics. Extensive investigations including ECG, MRI brain and CSF studies were performed and revealed no significant abnormalities. Since 2012, there have been six cases of acute kidney injury due to Hantavirus infection in the UK. Two cases were from the Humber region and were exposure to wild rats and the other four were exposed to specially bred pet fancy rats. Hanta virus infections can cause mild flu like symptoms but two clinical syndromes are associated with severe disease including haemorrhagic fever with renal syndrome, which may be associated with thrombocytopenia and Hantavirus cardiopulmonary syndrome. Neuropsychological impairments reported following hantavirus pulmonary syndrome and following Puumala virus infection have been reported. Minor white matter lesions were found in about half of the patients investigated with MRI brain. Seoul virus has a global distribution owing to the dispersal of its carrier host rats, through global trade. Several ports in the region could explain the possible establishment of Seoul virus in local populations of rats in the Yorkshire and Humber region. The risk of infection for occupationally exposed groups is 1-3% compared to 32.9% for specialist pet rat owners. The report highlight’s the importance of routinely asking about pets in the family. We hope to raise awareness of the emergence of hantavirus infection in the UK, particularly in the Yorkshire and Humber region. Clinicians should consider hantavirus infection as a potential cause of febrile illness causing renal impairment in children. Awareness of the possible neuro-cognitive sequele would help the clinicians offer appropriate information and support to children and their families. Contacting Rare and Imported Pathogens Laboratory at Porton is a useful resource for clinicians in UK when they consider unusual infections.

Keywords: Seoul hantavirus in child Porton, UK Acute kidney injury

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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

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Authors: Roshni Raha, Kavya P., Gayathri M.

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India, with a humongous population, remains the world's poorest developing nation in terms of nutritional status, with iron deficiency anaemia (IDA) affecting the population. Despite efforts over the past decades, India's anaemia prevalence has not been reduced. Researchers are interested in developing therapies that will minimize the typical side effects of oral iron and optimize iron salts-based treatment through delivery methods based on the physiology of hepcidin regulation. However, they need to come up with iron therapies that will prevent making the infection worse. This article explores using bio-nanotechnology as the alternative, promising substitution of providing iron supplements for the treatment of diarrhoea and gut inflammation in kids and pregnant women. This article is an exploratory study using a literature survey and secondary research from review papers. In the realm of biotechnology, nanoparticles have become extremely famous due to unexpected variations in surface characteristics caused by particle size. Particle size distribution and shape exhibit unusual, enhanced characteristics when reduced to nanoscale. The article attempts to develop a model for a nanotechnology based solution in iron fortification to combat the problems of diarrhoea and gut inflammation. Certain dimensions that have been considered in the model include the size, shape, source, and biosynthesis of the iron nanoparticles. Another area of investigation addressed in the article is the cost-effective biocompatible production of these iron nanoparticles. Studies have demonstrated that a substantial reduction of metal ions to form nanoparticles from the bulk metal occurs in plants because of the presence of a wide diversity of biomolecules. Using this concept, the paper investigates the effectiveness and impact of how similar sources can be used for the biological synthesis of iron nanoparticles. Results showed that iron particles, when prepared in nano-metre size, offer potential advantages. When the particle size of the iron compound decreases and attains nano configuration, its surface area increases, which further improves its solubility in the gastric acid, leading to higher absorption, higher bioavailability, and producing the least organoleptic changes in food. It has no negative effects and possesses a safe, effective profile to reduce IDA. Considering all the parameters, it has been concluded that iron particles in nano configuration serve as alternative iron supplements for the complete treatment of IDA. Nanoparticles of ferric phosphate, ferric pyrophosphate, and iron oxide are the choices of iron supplements. From a sourcing perspective, the paper concludes green sources are the primary sources for the biological synthesis of iron nanoparticles. It will also be a cost-effective strategy since our goal is to treat the target population in rural India. Bio-nanotechnology serves as an alternative and promising substitution for iron supplements due to its low cost, excellent bioavailability, and strong organoleptic properties. One area of future research can be to explore the type of size and shape of iron nanoparticles that would be suitable for the different age groups of pregnant women and children and whether it would be influenced based on the topography in certain areas.

Keywords: anemia, bio-nanotechnology, iron-fortification, nanoparticle

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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: Nancy Mackin

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Historically, architects from Aalto to Gaudi to Wright have looked to the architectural knowledge of long-resident peoples for forms and structural principles specifically adapted to the regional climate, geology, materials availability, and culture. In this research, structures traditionally built by Inuit peoples in a remote region of the Canadian high Arctic provides a folio of architectural ideas that are increasingly relevant during these times of escalating carbon emissions and climate change. ‘Green architecture from the Thawing Arctic’ researches, draws, models, and reconstructs traditional buildings of Inuit (Eskimo) peoples in three remote, often inaccessible Arctic communities. Structures verified in pre-contact oral history and early written history are first recorded in architectural drawings, then modeled and, with the participation of Inuit young people, local scientists, and Elders, reconstructed as emergency shelters. Three full-sized building types are constructed: a driftwood and turf-clad A-frame (spring/summer); a stone/bone/turf house with inwardly spiraling walls and a fan-shaped floor plan (autumn); and a parabolic/catenary arch-shaped dome from willow, turf, and skins (autumn/winter). Each reconstruction is filmed and featured in a short video. Communities found that the reconstructed buildings and the method of involving young people and Elders in the reconstructions have on-going usefulness, as follows: 1) The reconstructions provide emergency shelters, particularly needed as climate change worsens storms, floods, and freeze-thaw cycles and scientists and food harvesters who must work out of the land become stranded more frequently; 2) People from the communities re-learned from their Elders how to use materials from close at hand to construct impromptu shelters; 3) Forms from tradition, such as windbreaks at entrances and using levels to trap warmth within winter buildings, can be adapted and used in modern community buildings and housing; and 4) The project initiates much-needed educational and employment opportunities in the applied sciences (engineering and architecture), construction, and climate change monitoring, all offered in a culturally-responsive way. Elders, architects, scientists, and young people added innovations to the traditions as they worked, thereby suggesting new sustainable, culturally-meaningful building forms and materials combinations that can be used for modern buildings. Adding to the growing interest in bio-mimicry, participants looked at properties of Arctic and subarctic materials such as moss (insulation), shrub bark (waterproofing), and willow withes (parabolic and catenary arched forms). ‘Green Architecture from the Thawing Arctic’ demonstrates the effective, useful architectural oeuvre of a resilient northern people. The research parallels efforts elsewhere in the world to revitalize long-resident peoples’ architectural knowledge, in the interests of designing sustainable buildings that reflect culture, heritage, and identity.

Keywords: architectural culture and identity, climate change, forms from nature, Inuit architecture, locally sourced biodegradable materials, traditional architectural knowledge, traditional Inuit knowledge

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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

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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

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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

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Authors: D. Muyama, M. Luyiga, P. Buyungo, D. Chemonges, M. Namukwaya, L. Ssekabembe, B. Lukwago, D. Kyamagwa

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Context: The study focuses on the sustainability of health interventions in Uganda, particularly in the private sector, beyond donor-funded project periods. The Population Services International (PSI) implemented the Women Health Project (WHP) to ensure continued access to quality family planning, cervical cancer screening, and post-abortion care services through private clinics. Research Aim: The aim of the study is to assess the continued access to quality family planning, cervical cancer screening, and post-abortion care services through the private sector after the closure or reduction in funding of the WHP. Methodology: PSI trained and mentored 83 clinics to establish functional systems in self-regulatory quality improvement, supply chain, referral, and demand creation. The clinics were also connected to the national reporting system and utilized Ministry of Health reporting tools. An assessment tool with six criteria was designed and used to evaluate the progress of the clinics. Clinics scoring 75% and above were considered independent and graduated from the program. Findings: Out of the 83 private clinics, 56 successfully met the graduation criteria and graduated from the program, while 25 lost interest and were gradually dropped. Two clinics failed to achieve the criteria due to leadership challenges. The 59 graduating clinics continued to provide high-quality family planning services, including IUD, implant, Depo-Provera, oral contraceptives, and post-abortion care. All graduating clinics were reassessed and found to still be capable of offering services, attributing their success to government stock availability and acquired skills through mentorships. The clinics expressed appreciation to PSI for the sustainable plan that allowed them to operate beyond the project period. Theoretical Importance: This study contributes to the understanding of sustainability planning and the importance of clinic owners' attitudes and buy-in for continued service provision. It emphasizes the implementation of sustainability plans through existing structures to leverage available resources and ensure continuity of care. Data Collection and Analysis Procedures: The study collected data through the assessment tool that evaluated the progress of clinics based on the established criteria. The tool was scored out of 100%, and clinics scoring above 75% were deemed independent. The findings were analyzed quantitatively to determine the success rate of clinics in meeting the graduation criteria. Questions Addressed: The study addresses the question of whether private clinics in Uganda can sustain the provision of family planning, cervical cancer screening, and post-abortion care services after the closure or reduction in funding of the WHP. Conclusion: The study concludes that the attitude and buy-in of clinic owners are essential for sustainability planning. Implementing sustainability plans through existing structures and leveraging available resources are crucial for the continuity of care after the end of a project or reduced funding. The findings highlight the importance of establishing sustainable plans to ensure continued access to essential health services beyond the project period. Contributions: This study contributes to the existing knowledge for programmers implementing or intending to implement donor-funded projects. It provides insights into designing sustainable plans that enable the independent operation of clinics even after the end of a project.

Keywords: graduation, family planning, systems strengthening, sustainability

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Authors: Ali Baker, Russel Krawitz

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This paper describes a rare occurrence where a potentially fatal complication of COVID-19 infection (MIS-A) was misdiagnosed as an acute abdomen. As most patients with this syndrome present with fever and gastrointestinal symptoms, they may inadvertently fall under the care of the surgical unit. However, unusual imaging findings and a poor response to anti-microbial therapy should prompt clinicians to suspect a non-surgical etiology. More than half of MIS-A patients require ICU admission and vasopressor support. Prompt referral to a physician is key, as the cornerstone of treatment is IVIG and corticosteroid therapy. A 32 year old woman presented with right sided abdominal pain and fevers. She had also contracted COVID-19 two months earlier. Abdominal examination revealed generalised right sided tenderness. The patient had raised inflammatory markers, but other blood tests were unremarkable. CT scan revealed extensive lymphadenopathy along the ileocolic chain. The patient proved to be a diagnostic dilemma. She was reviewed by several surgical consultants and discussed with several inpatient teams. Although IV antibiotics were commenced, the right sided abdominal pain, and fevers persisted. Pan-culture returned negative. A mild cholestatic derangement developed. On day 5, the patient underwent preparation for colonoscopy to assess for a potential intraluminal etiology. The following day, the patient developed sinus tachycardia and hypotension that was refractory to fluid resuscitation. That patient was transferred to ICU and required vasopressor support. Repeat CT showed peri-portal edema and a thickened gallbladder wall. On re-examination, the patient was Murphy’s sign positive. Biliary ultrasound was equivocal for cholecystitis. The patient was planned for diagnostic laparoscopy. The following morning, a marked rise in cardiac troponin was discovered, and a follow-up echocardiogram revealed moderate to severe global systolic dysfunction. The impression was post-COVID MIS with myocardial involvement. IVIG and Methylprednisolone infusions were commenced. The patient had a great response. Vasopressor support was weaned, and the patient was discharged from ICU. The patient continued to improve clinically with oral prednisolone, and was discharged on day 17. Although MIS following COVID-19 infection is well-described syndrome in children, only recently has it come to light that it can occur in adults. The exact incidence is unknown, but it is thought to be rare. A recent systematic review found only 221 cases of MIS-A, which could be included for analysis. Symptoms vary, but the most frequent include fever, gastrointestinal, and mucocutaneous. Many patients progress to multi-organ failure and require vasopressor support. 7% succumb to the illness. The pathophysiology of MIS is only partly understood. It shares similarities with Kawasaki disease, macrophage activation syndrome, and cytokine release syndrome. Importantly, by definition, the patient must have an absence of severe respiratory symptoms. It is thought to be due to a dysregulated immune response to the virus. Potential mechanisms include reduced levels of neutralising antibodies and autoreactive antibodies that promote inflammation. Further research into MIS-A is needed. Although rare, this potentially fatal syndrome should be considered in the unwell surgical patient who has recently contracted COVID-19 and poses a diagnostic dilemma.

Keywords: acute-abdomen, MIS, COVID-19, ICU

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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

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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: Ankita Baidya, Vanishri Ganakumar, Ranveer S. Jadon, Piyush Ranjan, Rita Sood

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Septic embolism can have varied presentations and clinical considerations. Infected central venous catheters are commonly associated with septic emboli but peripheral vascular catheters are rarely implicated. We describe a rare case of septic pulmonary emboli related to infected peripheral venous cannulation caused by an unusual etiological agent. A young male presented with complaints of fever, productive cough, sudden onset shortness of breath and cellulitis in both the upper limbs. He was recently hospitalised for dengue fever and administered intravenous fluids through peripheral venous line. The patient was febrile, tachypneic and in respiratory distress, there were multiple pus filled bullae in left hand alongwith swelling and erythema involving right forearm that started at the site of cannulation. Chest examination showed active accessory muscles of respiration, stony dull percussion at the base of right lung and decreased breath sounds at right infrascapular, infraaxillary and mammary area. Other system examination was within normal limits. Chest X-ray revealed bilateral multiple patchy heterogenous peripheral opacities and infiltrates with right-sided pleural effusion. Contrast-enhanced computed tomography (CECT) chest showed feeding vessel sign confirming the diagnosis as septic emboli. Venous Doppler and 2D-echocardiogarm were normal. Laboratory findings showed marked leucocytosis (22000/mm3). Pus aspirate, blood sample, and sputum sample were sent for microbiological testing. The patient was started empirically on ceftriaxone, vancomycin, and clindamycin. The Pus culture and sputum culture showed Klebsiella pneumoniae sensitive to cefoperazone-sulbactum, piperacillin-tazobactum, meropenem and amikacin. The antibiotics were modified accordingly to antimicrobial sensitivity profile to Cefoperazone-sulbactum. Bronchoalveolar lavage (BAL) was done and sent for microbiological investigations. BAL culture showed Klebsiella pneumoniae with same antimicrobial resistance profile. On day 6 of starting cefoperazone-sulbactum, he became afebrile. The skin lesions improved significantly. He was administered 2 weeks of cefoperazone–sulbactum and discharged on oral faropenem for 4 weeks. At the time of discharge, TLC was 11200/mm3 with marked radiological resolution of infection and healed skin lesions. He was kept in regular follow up. Chest X-ray and skin lesions showed complete resolution after 8 weeks. Till date, only couple of case reports of septic emboli through peripheral intravenous line have been reported in English literature. This case highlights that a simple procedure of peripheral intravenous cannulation can lead to catastrophic complication of septic pulmonary emboli and widespread cellulitis if not done with proper care and precautions. Also, the usual pathogens in such clinical settings are gram positive bacteria, but with the history of recent hospitalization, empirical therapy should also cover drug resistant gram negative microorganisms. It also emphasise the importance of appropriate healthcare practices to be taken care during all procedures.

Keywords: antibiotics, cannula, Klebsiella pneumoniae, septic emboli

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Authors: Sophy Joseph

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The study uses the concept of ‘Settler city’ to understand the nature of peripheralization that a neoliberal city initiates. The settler city designs powerless communities without inherent rights, title and sovereignty. Kathputli Colony, home to generations of artists/craftsmen, who have kept heritage of arts/crafts alive, has undergone eviction of its population from urban space. The proposed study, ‘Neoliberal Settler City: Socio-spatial segregation and livelihood of artists/craftsmen in Delhi’ would problematize the settler city as a colonial technology. The colonial regime has ‘erased’ the ‘unwanted’ as primitive and swept them to peripheries in the city. This study would also highlight how structural change in political economy has undermined their crafts/arts by depriving them from practicing/performing it with dignity in urban space. The interconnections between citizenship and In-Situ Private Public Partnership in Kathputli rehabilitation has become part of academic exercise. However, a comprehensive study connecting inherent characteristics of neoliberal settler city, trajectory of political economy of unorganized workers - artists/craftsmen and legal containment and exclusion leading to dispossession and marginalization of communities from the city site, is relevant to contextualize the trauma of spatial segregation. This study would deal with political, cultural, social and economic dominant behavior of the structure in the state formation, accumulation of property and design of urban space, fueled by segregation of marginalized/unorganized communities and disowning the ‘footloose proletariat’, the migrant workforce. The methodology of study involves qualitative research amongst communities and the field work-oral testimonies and personal accounts- becomes the primary material to theorize the realities. The secondary materials in the forms of archival materials about historical evolution of Delhi as a planned city from various archives, would be used. As the study also adopt ‘narrative approach’ in qualitative study, the life experiences of craftsmen/artists as performers and emotional trauma of losing their livelihood and space forms an important record to understand the instability and insecurity that marginalization and development attributes on urban poor. The study attempts to prove that though there was a change in political tradition from colonialism to constitutional democracy, new state still follows the policy of segregation and dispossession of the communities. It is this dispossession from the space, deprivation of livelihood and non-consultative process in rehabilitation that reflects the neoliberal approach of the state and also critical findings in the study. This study would entail critical spatial lens analyzing ethnographic and sociological data, representational practices and development debates to understand ‘urban otherization’ against craftsmen/artists. This seeks to develop a conceptual framework for understanding the resistance of communities against primitivity attached with them and to decolonize the city. This would help to contextualize the demand for declaring Kathputli Colony as ‘heritage artists village’. The conceptualization and contextualization would help to argue for right to city of the communities, collective rights to property, services and self-determination. The aspirations of the communities also help to draw normative orientation towards decolonization. It is important to study this site as part of the framework, ‘inclusive cities’ because cities are rarely noted as important sites of ‘community struggles’.

Keywords: neoliberal settler city, socio-spatial segregation, the livelihood of artists/craftsmen, dispossession of indigenous communities, urban planning and cultural uprooting

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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: Jen Wang, Wei-Chia Hsu, Zih-Sin Wang, Ching-Ping Chu, Bo-Shiou Guo

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In the late 19th century, the Jinguashi ore deposit in northern Taiwan was discovered, and accompanied with flourishing mining activities. However, tons of contaminants including heavy metals, sulfur dioxide, and total petroleum hydrocarbons (TPH) were released to surroundings and caused environmental problems. Site T was one of copper smelter located on the coastal hill near Jinguashi ore deposit. In over ten years of operation, variety contaminants were emitted that it polluted the surrounding soil and groundwater quality. In order to exhaust fumes produced from smelting process, three stacks were built along the hill behind the factory. The sediment inside the stacks contains high concentration of heavy metals such as arsenic, lead, copper, etc. Moreover, soil around the discarded stacks suffered a serious contamination when deposition leached from the ruptures of stacks. Consequently, Site T (including the factory and its surroundings) was declared as a pollution remediation site that visiting the site and land-use activities on it are forbidden. However, the natural landscape and cultural attractions of Site T are spectacular that it attracts a lot of visitors annually. Moreover, land resources are extremely precious in Taiwan. In addition, Taiwan Environmental Protection Administration (EPA) is actively promoting the contaminated land revitalization policy. Therefore, this study took Site T as case study for brownfield revitalization planning to the limits of activate and remediate the natural resources. Land-use suitability analysis and risk mapping were applied in this study to make appropriate risk management measures and redevelopment plan for the site. In land-use suitability analysis, surrounding factors into consideration such as environmentally sensitive areas, biological resources, land use, contamination, culture, and landscapes were collected to assess the development of each area; health risk mapping was introduced to show the image of risk assessments results based on the site contamination investigation. According to land-use suitability analysis, the site was divided into four zones: priority area (for high-efficiency development), secondary area (for co-development with priority area), conditional area (for reusing existing building) and limited area (for Eco-tourism and education). According to the investigation, polychlorinated biphenyls (PCB), heavy metals and TPH were considered as target contaminants while oral, inhalation and dermal would be the major exposure pathways in health risk assessment. In accordance with health risk map, the highest risk was found in the southwest and eastern side. Based on the results, the development plan focused on zoning and land use. Site T was recommended be divides to public facility zone, public architectonic art zone, viewing zone, existing building preservation zone, historic building zone, and cultural landscape zone for various purpose. In addition, risk management measures including sustained remediation, extinguish exposure and administration management are applied to ensure particular places are suitable for visiting and protect the visitors’ health. The consolidated results are corroborated available by analyzing aspects of law, land acquired method, maintenance and management and public participation. Therefore, this study has a certain reference value to promote the contaminated land revitalization policy in Taiwan.

Keywords: brownfield revitalization, land-use suitability analysis, health risk map, risk management

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Authors: T. Schilirò, S. Bonetta, S. Bonetta, E. Ceretti, D. Feretti, I. Zerbini, V. Romanazzi, S. Levorato, T. Salvatori, S. Vannini, M. Verani, C. Pignata, F. Bagordo, G. Gilli, S. Bonizzoni, A. Bonetti, E. Carraro, U. Gelatti

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Air pollution is one of the most important worldwide health concern. In the last years, in both the US and Europe, new directives and regulations supporting more restrictive pollution limits were published. However, the early effects of air pollution occur, especially for the urban population. Several epidemiological and toxicological studies have documented the remarkable effect of particulate matter (PM) in increasing morbidity and mortality for cardiovascular disease, lung cancer and natural cause mortality. The finest fractions of PM (PM with aerodynamic diameter <2.5 µm and less) play a major role in causing chronic diseases. The International Agency for Research on Cancer (IARC) has recently classified air pollution and fine PM as carcinogenic to human (1 Group). The structure and composition of PM influence the biological properties of particles. The chemical composition varies with season and region of sampling, photochemical-meteorological conditions and sources of emissions. The aim of the MAPEC (Monitoring Air Pollution Effects on Children for supporting public health policy) study is to evaluate the associations between air pollution and biomarkers of early biological effects in oral mucosa cells of 6-8 year old children recruited from first grade schools. The study was performed in five Italian towns (Brescia, Torino, Lecce, Perugia and Pisa) characterized by different levels of airborne PM (PM10 annual average from 44 µg/m3 measured in Torino to 20 µg/m3 measured in Lecce). Two to five schools for each town were chosen to evaluate the variability of pollution within the same town. Child exposure to urban air pollution was evaluated by collecting ultrafine PM (PM0.5) in the school area, on the same day of biological sampling. PM samples were collected for 72h using a high-volume gravimetric air sampler and glass fiber filters in two different seasons (winter and spring). Gravimetric analysis of the collected filters was performed; PM0.5 organic extracts were chemically analyzed (PAH, Nitro-PAH) and tested on A549 by the Comet assay and Micronucleus test and on Salmonella strains (TA100, TA98, TA98NR and YG1021) by Ames test. Results showed that PM0.5 represents a high variable PM10 percentage (range 19.6-63%). PM10 concentration were generally lower than 50µg/m3 (EU daily limit). All PM0.5 extracts showed a mutagenic effect with TA98 strain (net revertant/m3 range 0.3-1.5) and suggested the presence of indirect mutagens, while lower effect was observed with TA100 strain. The results with the TA98NR and YG1021 strains showed the presence of nitroaromatic compounds as confirmed by the chemical analysis. No genotoxic or oxidative effect of PM0.5 extracts was observed using the comet assay (with/without Fpg enzyme) and micronucleus test except for some sporadic samples. The low biological effect observed could be related to the low level of air pollution observed in this winter sampling associated to a high atmospheric instability. For a greater understanding of the relationship between PM size, composition and biological effects the results obtained in this study suggest to investigate the biological effect of the other PM fractions and in particular of the PM0.5-1 fraction.

Keywords: airborne PM, ames test, comet assay, micronucleus test

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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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