Search results for: progressive%20multifocal%20leukoencephalopathy%20%28PML%29

Authors: Sadandaula Rose Muheriwa Matemba, Alexander Glazier, Natalie M. LeBlanc

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In the United States, up to 10% of girls and 22 % of boys 10-14 years have had sex, 5% of them had their first sex before 11 years, and the age of first sexual encounter is reported to be 8 years. Over 4,000 adolescent girls, 10-14 years, become pregnant every year, and 2.6% of the abortions in 2019 were among adolescents below 15 years. Despite these negative outcomes, little research has been conducted to understand the sexual health education offered to young adolescents ages 10-14. Early sexual health education is one of the most effective strategies to help lower the rate of early pregnancies, HIV infections, and other sexually transmitted. Such knowledge is necessary to inform best practices for supporting the healthy sexual development of young adolescents and prevent adverse outcomes. This qualitative descriptive study was conducted to explore the community stakeholders’ experiences in sexual health education for young adolescents ages 10-14 and ascertain the young adolescents’ sexual health support needs. Maximum variation purposive sampling was used to recruit a total sample of 13 community stakeholders, including health education teachers, members of youth-based organizations, and Adolescent Clinic providers in Rochester, New York State, in the United States of America from April to June 2022. Data were collected through semi-structured individual in-depth interviews and were analyzed using MAXQDA following a conventional content analysis approach. Triangulation, team analysis, and respondent validation to enhance rigor were also employed to enhance study rigor. The participants were predominantly female (92.3%) and comprised of Caucasians (53.8%), Black/African Americans (38.5%), and Indian-American (7.7%), with ages ranging from 23-59. Four themes emerged: the perceived need for early sexual health education, preferred timing to initiate sexual health conversations, perceived age-appropriate content for young adolescents, and initiating sexual health conversations with young adolescents. The participants described encouraging and concerning experiences. Most participants were concerned that young adolescents are living in a sexually driven environment and are not given the sexual health education they need, even though they are open to learning sexual health materials. There was consensus on the need to initiate sexual health conversations early at 4 years or younger, standardize sexual health education in schools and make age-appropriate sexual health education progressive. These results show that early sexual health education is essential if young adolescents are to delay sexual debut, prevent early pregnancies, and if the goal of ending the HIV epidemic is to be achieved. However, research is needed on a larger scale to understand how best to implement sexual health education among young adolescents and to inform interventions for implementing contextually-relevant sexuality education for this population. These findings call for increased multidisciplinary efforts in promoting early sexual health education for young adolescents.

Keywords: community stakeholders’ perspectives, sexual development, sexual health education, young adolescents

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Authors: Joao Barbosa

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After an intense dispute between the big bang cosmology and its big rival, the steady-state cosmology, some important experimental observations, such as the determination of helium abundance in the universe and the discovery of the cosmic background radiation in the 1960s were decisive for the progressive and wide acceptance of big bang cosmology and the inevitable abandonment of steady-state cosmology. But, despite solid theoretical support and those solid experimental observations favorable to big bang cosmology, Fred Hoyle, one of the proponents of the steady-state and the main opponent of the idea of the big bang (which, paradoxically, himself he baptized), never gave up and continued to fight for the idea of a stationary (or quasi-stationary) universe until the end of his life, even after decades of widespread consensus around the big bang cosmology. We can try to understand this persistent attitude of Hoyle by applying Holton’s thematic analysis to cosmology. Holton recognizes in the scientific activity a dimension that, even unconscious or not assumed, is nevertheless very important in the work of scientists, in implicit articulation with the experimental and the theoretical dimensions of science. This is the thematic dimension, constituted by themata – concepts, methodologies, and hypotheses with a metaphysical, aesthetic, logical, or epistemological nature, associated both with the cultural context and the individual psychology of scientists. In practice, themata can be expressed through personal preferences and choices that guide the individual and collective work of scientists. Thematic analysis shows that big bang cosmology is mainly based on a set of themata consisting of evolution, finitude, life cycle, and change; the cosmology of the steady-state is based on opposite themata: steady-state, infinity, continuous existence, and constancy. The passionate controversy that these cosmological views carried out is part of an old cosmological opposition: the thematic opposition between an evolutionary view of the world (associated with Heraclitus) and a stationary view (associated with Parmenides). Personal preferences seem to have been important in this (thematic) controversy, and the thematic analysis that was developed shows that Hoyle is a very illustrative example of a life-long personal commitment to some themata, in this case to the opposite themata of the big bang cosmology. His struggle against the big bang idea was strongly based on philosophical and even religious reasons – which, in a certain sense and in a Holtonian perspective, is related to thematic preferences. In this personal and persistent struggle, Hoyle always refused the way how some experimental observations were considered decisive in favor of the big bang idea, arguing that the success of this idea is based on sociological and cultural prejudices. This Hoyle’s attitude is a personal thematic attitude, in which the acceptance or rejection of what is presented as proof or scientific fact is conditioned by themata: what is a proof or a scientific fact for one scientist is something yet to be established for another scientist who defends different or even opposites themata.

Keywords: cosmology, experimental observations, fred hoyle, interpretation, life-long personal commitment, Themata

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Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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Authors: Paritosh Goel

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The conservation of historic buildings and historic Centre’s over recent years has become fully encompassed in the planning of built-up areas and their management following climate changes. The approach of the world of restoration, in the Indian context on integrated urban regeneration and its strategic potential for a smarter, more sustainable and socially inclusive urban development introduces, for urban transformations in general (historical centers and otherwise), the theme of sustainability. From this viewpoint, it envisages, as a primary objective, a real “green, ecological or environmental” requalification of the city through interventions within the main categories of sustainability: mobility, energy efficiency, use of sources of renewable energy, urban metabolism (waste, water, territory, etc.) and natural environment. With this the concept of a “resilient city” is also introduced, which can adapt through progressive transformations to situations of change which may not be predictable, behavior that the historical city has always been able to express. Urban planning on the other hand, has increasingly focused on analyses oriented towards the taxonomic description of social/economic and perceptive parameters. It is connected with human behavior, mobility and the characterization of the consumption of resources, in terms of quantity even before quality to inform the city design process, which for ancient fabrics, and mainly affects the public space also in its social dimension. An exact definition of the term “smart city” is still essentially elusive, since we can attribute three dimensions to the term: a) That of a virtual city, evolved based on digital networks and web networks b) That of a physical construction determined by urban planning based on infrastructural innovation, which in the case of historic Centre’s implies regeneration that stimulates and sometimes changes the existing fabric; c) That of a political and social/economic project guided by a dynamic process that provides new behavior and requirements of the city communities that orients the future planning of cities also through participation in their management. This paper is a preliminary research into the connections between these three dimensions applied to the specific case of the fabric of ancient cities with the aim of obtaining a scientific theory and methodology to apply to the regeneration of Indian historical Centre’s. The Smart city scheme if contextualize with heritage of the city it can be an initiative which intends to provide a transdisciplinary approach between various research networks (natural sciences, socio-economics sciences and humanities, technological disciplines, digital infrastructures) which are united in order to improve the design, livability and understanding of urban environment and high historical/cultural performance levels.

Keywords: historical cities regeneration, sustainable restoration, urban planning, smart cities, cultural heritage development strategies

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Authors: A. Pallavi, N. Vijay Mohan

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A nation can be economically progressive only when the citizens have sufficient capacity to work efficiently to increase the productivity. So, good health must be regarded as a primary need of the community. This helps the growth and development of the body and the mind, which in turn leads to progress and prosperity of the nation. An optimum growth is a necessity for an efficient existence in a biologically adverse and economically competitive world. It is also necessary for the execution of daily routine work. Yoga is a method or a system for the complete development of the personality in a human being. It can be further elaborated as an all-around and complete development of the body, mind, morality, intellect and soul of a being. Sri Aurobindo defines yoga as 'a methodical effort towards self-perfection by the development of the potentialities in the individual.' Aerobic exercise as any activity that uses large muscle groups, can be maintained continuously, and is rhythmic I nature. It is a type of exercise that overloads the heart and lungs and causes them to work harder than at rest. The important idea behind aerobic exercise today, is to get up and get moving. There are more activities that ever to choose from, whether it is a new activity or an old one. Find something you enjoy doing that keeps our heart rate elevated for a continuous time period and get moving to a healthier life. Middle aged selected and served as the subjects for the purpose of this study. The selected subjects were in the age group of 30 to 40 years. By going through the literature and after consulting the experts in yoga and aerobic training, the investigator had chosen the variables which are specifically related to the middle-aged men. The selected physiological variables are pulse rate, diastolic blood pressure, systolic blood pressure; percent body fat and vital capacity. The selected psychological variables are job anxiety, occupational stress. The study was formulated as a random group design consisting of aerobic exercise and yogic exercises groups. The subjects (N=60) were at random divided into three equal groups of twenty middle-aged men each. The groups were assigned the names as follows: 1. Experimental group I- aerobic exercises group, 2. Experimental group II- yogic exercises, 3. Control group. All the groups were subjected to pre-test prior to the experimental treatment. The experimental groups participated in their respective duration of twenty-four weeks, six days in a week throughout the study. The various tests administered were: prior to training (pre-test), after twelfth week (second test) and twenty-fourth weeks (post-test) of the training schedule.

Keywords: pulse rate, diastolic blood pressure, systolic blood pressure; percent body fat and vital capacity, psychological variables, job anxiety, occupational stress, aerobic exercise, yogic exercise

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Authors: Geum Yeon Sim, Jasal Patel, Anand Kumthekar, Stanley Wainapel

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A 65-year-old right-hand dominant African-American man, formerly employed as a security guard, was referred to Rehabilitation Medicine with bilateral hand stiffness and weakness. His past medical history was only significant for myelofibrosis, diagnosed 4 years earlier, for which he was receiving scheduled blood transfusions. Approximately 2 years ago, he began to notice stiffness and swelling in his non-dominant hand that progressed to pain and decreased strength, limiting his hand function. Similar but milder symptoms developed in his right hand several months later. There was no history of prior injury or exposure to cold. Physical examination showed enlargement of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with finger flexion contractures, Swan-neck and Boutonniere deformities, and associated joint tenderness. Changes were more prominent in the left hand. X-rays showed mild osteoarthritis of several bilateral PIP joints. Anti-nuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies were negative. MRI of the hand showed no erosions or synovitis. A rheumatology consultation was obtained, and the cause of his symptoms was attributed to myelofibrosis-related arthropathy with secondary osteoarthritis. The patient was tried on diclofenac cream and received a few courses of Occupational Therapy with limited functional improvement. Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Rheumatic manifestations of malignancies include direct invasion, paraneoplastic presentations, secondary gout, or hypertrophic osteoarthropathy. PMF causes gradual bone marrow fibrosis with extramedullary metaplastic hematopoiesis in the liver, spleen, or lymph nodes. Musculoskeletal symptoms are not common and are not well described in the literature. The first reported case of myelofibrosis related arthritis was seronegative arthritis due to synovial invasion of myeloproliferative elements. Myelofibrosis has been associated with autoimmune diseases such as systemic lupus erythematosus, progressive systemic sclerosis, and rheumatoid arthritis. Gout has been reported in patients with myelofibrosis, and the underlying mechanism is thought to be related to the high turnover of nucleic acids that is greatly augmented in this disease. X-ray findings in these patients usually include erosive arthritis with synovitis. Treatment of underlying PMF is the treatment of choice, along with anti-inflammatory medications. Physicians should be cognizant of recognizing this rare entity in patients with PMF while maintaining clinical suspicion for more common causes of joint deformities, such as rheumatic diseases.

Keywords: myelofibrosis, arthritis, arthralgia, malignancy

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Authors: Meenalochana Inguva

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The context: The Center for Preparatory study is one of the strongest and most vibrant academic teaching units of the Sultan Qaboos University (SQU). The Foundation Programme English Language (FPEL) is part of a larger foundation programme which was implemented at SQU in fall 2010. The programme has been designed to prepare the students who have been accepted to study in the university in order to achieve the required educational goals (the learning outcomes) that have been designed according to Oman Academic Standards and published by the Omani Authority for Academic Accreditation (OAAA) for the English language component. The curriculum: At the CPS, the English language curriculum is based on the learning outcomes drafted for each level. These learning outcomes guide the students in meeting what is expected of them by the end of each level. These six levels are progressive in nature and are seen as a continuum. The study: A periodic evaluation of language programmes is necessary to improve the quality of the programmes and to meet the set goals of the programmes. An evaluation may be carried out internally or externally depending on the purpose and context. A self-study programme was initiated at the beginning of spring semester 2015 with a team comprising a total of 11 members who worked with-in the assigned course areas (level and programme specific). Only areas specific to FPEL have been included in the study. The study was divided into smaller tasks and members focused on their assigned courses. The self-study primarily focused on analyzing the programme LOs, curriculum planning, materials used and their relevance against the GFP exit standards. The review team also reflected on the assessment methods and procedures followed to reflect on student learning. The team has paid attention to having standard criteria for assessment and transparency in procedures. A special attention was paid to the staging of LOs across levels to determine students’ language and study skills ability to cope with higher level courses. Findings: The findings showed that most of the LOs are met through the materials used for teaching. Students score low on objective tests and high on subjective tests. Motivated students take advantage of academic support activities others do not utilize the student support activities to their advantage. Reading should get more hours. In listening, the format of the listening materials in CT 2 does not match the test format. Some of the course materials need revision. For e.g. APA citation, referencing etc. No specific time is allotted for teaching grammar Conclusion: The findings resulted in taking actions in bridging gaps. It will also help the center to be better prepared for the external review of its FPEL curriculum. It will also provide a useful base to prepare for the self-study portfolio for GFP standards assessment and future audit.

Keywords: curriculum planning, learning outcomes, reflections, self-evaluation

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Authors: Natalia Politaeva, Iuliia Smiatskaia, Iuliia Bazarnova, Iryna Atamaniuk, Kerstin Kuchta

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Nowadays, the progressive decrease of primary natural resources and ongoing upward trend in terms of energy demand, have resulted in development of new generation technological processes which are focused on step-wise production and residues utilization. Thus, microalgae-based 3^rd generation bioeconomy is considered one of the most promising approaches that allow production of value-added products and sophisticated utilization of residues biomass. In comparison to conventional biomass, microalgae can be cultivated in wide range of conditions without compromising food and feed production, and thus, addressing issues associated with negative social and environmental impacts. However, one of the most challenging tasks is to undergo seasonal variations and to achieve optimal growing conditions for indoor closed systems that can cover further demand for material and energetic utilization of microalgae. For instance, outdoor cultivation in St. Petersburg (Russia) is only suitable within rather narrow time frame (from mid-May to mid-September). At earlier and later periods, insufficient sunlight and heat for the growth of microalgae were detected. On the other hand, without additional physical effects, the biomass increment in summer is 3-5 times per week, depending on the solar radiation and the ambient temperature. In order to increase biomass production, scientists from all over the world have proposed various technical solutions for cultivators and have been studying the influence of various physical factors affecting biomass growth namely: magnetic field, radiation impact, and electric field, etc. In this paper, the influence of infrared radiation (IR) and fluorescent light on the growth rate of microalgae Chlorella sorokiniana has been studied. The cultivation of Chlorella sorokiniana was carried out in 500 ml cylindrical glass vessels, which were constantly aerated. To accelerate the cultivation process, the mixture was stirred for 15 minutes at 500 rpm following 120 minutes of rest time. At the same time, the metabolic needs in nutrients were provided by the addition of micro- and macro-nutrients in the microalgae growing medium. Lighting was provided by fluorescent lamps with the intensity of 2500 ± 300 lx. The influence of IR was determined using IR lamps with a voltage of 220 V, power of 250 W, in order to achieve the intensity of 13 600 ± 500 lx. The obtained results show that under the influence of fluorescent lamps along with the combined effect of active aeration and variable mixing, the biomass increment on the 2^nd day was three times, and on the 7^th day, it was eight-fold. The growth rate of microalgae under the influence of IR radiation was lower and has reached 22.6·10⁶ cells·mL^-1. However, application of IR lamps for the biomass growth allows maintaining the optimal temperature of microalgae suspension at approximately 25-28°C, which might especially be beneficial during the cold season in extreme climate zones.

Keywords: biomass, fluorescent lamp, infrared radiation, microalgae

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Authors: Mudasir Ahmad Syed, Raashid Ahmd Wani, Mashooq Ahmad Dar, Uneeb Urwat, Riaz Ahmad Shah, Nazir Ahmad Ganai

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Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses. However, the Salmonella Typhimurium is also able to cause infection in humans, described by typhoid fever and acute gastro-intestinal disease. A study was conducted at days to investigate pathological, histopathological, haemato-biochemical, immunological and expression kinetics of NRAMP (natural resistance associated macrophage protein) gene family (NRAMP1 and NRAMP2) in broiler chickens following experimental infection of Salmonella Typhimurium at 0,1,3,5,7,9,11,13 and 15 days respectively. Infection was developed in birds through oral route at 2×108 CFU/ml. Clinical symptoms appeared 4 days post infection (dpi) and after one-week birds showed progressive weakness, anorexia, diarrhea and lowering of head. On postmortem examination, liver showed congestion, hemorrhage and necrotic foci on surface, while as spleen, lungs and intestines revealed congestion and hemorrhages. Histopathological alterations were principally observed in liver in second week post infection. Changes in liver comprised of congestion, areas of necrosis, reticular endothelial hyperplasia in association with mononuclear cell and heterophilic infiltration. Hematological studies confirm a significant decrease (P<0.05) in RBC count, Hb concentration and PCV. White blood cell count showed significant increase throughout the experimental study. An increase in heterophils was found up to 7dpi and a decreased pattern was observed afterwards. Initial lymphopenia followed by lymphocytosis was found in infected chicks. Biochemical studies showed a significant increase in glucose, AST and ALT concentration and a significant decrease (P<0.05) in total protein and albumin level in the infected group. Immunological studies showed higher titers of IgG in infected group as compared to control group. The real time gene expression of NRAMPI and NRAMP2 genes increased significantly (P<0.05) in infected group as compared to controls. The peak expression of NRAMP1 gene was seen in liver, spleen and caecum of infected birds at 3dpi, 5dpi and 7dpi respectively, while as peak expression of NRAMP2 gene in liver, spleen and caecum of infected chicken was seen at 9dpi, 5dpi and 9dpi respectively. This study has role in diagnostics and prognostics in the poultry industry for the detection of salmonella infections at early stages of poultry development.

Keywords: biochemistry, histopathology, NRAMP, poultry, real time expression, Salmonella Typhimurium

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Authors: Maciej Szeląg, Stanisław Fic

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The impact of elevated temperatures on the construction materials manifests in change of their physical and mechanical characteristics. Stresses and thermal deformations that occur inside the volume of the material cause its progressive degradation as temperature increase. Finally, the reactions and transformations of multiphase structure of cementitious composite cause its complete destruction. A particularly dangerous phenomenon is the impact of thermal shock – a sudden high temperature load. The thermal shock leads to a high value of the temperature gradient between the outer surface and the interior of the element in a relatively short time. The result of mentioned above process is the formation of the cracks and scratches on the material’s surface and inside the material. The article describes the use of computer image analysis techniques to identify and assess the structure of the cluster cracks on the surfaces of modified cement pastes, caused by thermal shock. Four series of specimens were tested. Two Portland cements were used (CEM I 42.5R and CEM I 52,5R). In addition, two of the series contained metakaolinite as a replacement for 10% of the cement content. Samples in each series were made in combination of three w/b (water/binder) indicators of respectively 0.4; 0.5; 0.6. Surface cracks of the samples were created by a sudden temperature load at 200°C for 4 hours. Images of the cracked surfaces were obtained via scanning at 1200 DPI; digital processing and measurements were performed using ImageJ v. 1.46r software. In order to examine the cracked surface of the cement paste as a system of closed clusters – the dispersal systems theory was used to describe the structure of cement paste. Water is used as the dispersing phase, and the binder is used as the dispersed phase – which is the initial stage of cement paste structure creation. A cluster itself is considered to be the area on the specimen surface that is limited by cracks (created by sudden temperature loading) or by the edge of the sample. To describe the structure of cracks two stereological parameters were proposed: A ̅ – the cluster average area, L ̅ – the cluster average perimeter. The goal of this study was to compare the investigated stereological parameters with the mechanical properties of the tested specimens. Compressive and tensile strength testes were carried out according to EN standards. The method used in the study allowed the quantitative determination of defects occurring in the examined modified cement pastes surfaces. Based on the results, it was found that the nature of the cracks depends mainly on the physical parameters of the cement and the intermolecular interactions on the dispersal environment. Additionally, it was noted that the A ̅/L ̅ relation of created clusters can be described as one function for all tested samples. This fact testifies about the constant geometry of the thermal cracks regardless of the presence of metakaolinite, the type of cement and the w/b ratio.

Keywords: cement paste, cluster cracks, elevated temperature, image analysis, metakaolinite, stereological parameters

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Authors: Tashinga Matindike

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By means of definition, digital artworks encompass an array of artistic productions that are expressed in a technological form as an essential part of a creative process. Examples include illustrations, photos, videos, sculptures, and installations. Within the context of the visual arts, the process of repatriation involves the return of once-appropriated goods. Archiving denotes the preservation of a commodity for storage purposes in order to nurture its continuity. The aforementioned definitions form the foundation of the academic framework and premise of the argument, which is outlined in this paper. This paper aims to define, discuss and decipher the complexities involved in digitising artworks, whilst explaining the benefits of the process, particularly within the South African context, which is rich in tangible and intangible traditional cultural material, objects, and performances. With the internet having been introduced to the African Continent in the early 1990s, this new form of technology, in its own right, initiated a high degree of efficiency, which also resulted in the progressive transformation of computer-generated visual output. Subsequently, this caused a revolutionary influence on the manner in which technological software was developed and uterlised in art-making. Digital technology and the digitisation of creative processes then opened up new avenues of collating and recording information. One of the first visual artists to make use of digital technology software in his creative productions was United States-based artist John Whitney. His inventive work contributed greatly to the onset and development of digital animation. Comparable by technique and originality, South African contemporary visual artists who make digital artworks, both locally and internationally, include David Goldblatt, Katherine Bull, Fritha Langerman, David Masoga, Zinhle Sethebe, Alicia Mcfadzean, Ivan Van Der Walt, Siobhan Twomey, and Fhatuwani Mukheli. In conclusion, the main objective of this paper is to address the following questions: In which ways has the South African art community of visual artists made use of and benefited from technology, in its digital form, as a means to further advance creativity? What are the positive changes that have resulted in art production in South Africa since the onset and use of digital technological software? How has digitisation changed the manner in which we record, interpret, and archive both written and visual information? What is the role of South African art institutions in the development of digital technology and its use in the field of visual art. What role does digitisation play in the process of the repatriation of artworks and artefacts. The methodology in terms of the research process of this paper takes on a multifacted form, inclusive of data analysis of information attained by means of qualitative and quantitative approaches.

Keywords: digital art, digitisation, technology, archiving, transformation and repatriation

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Authors: Hamed Delrobai Ghoochan Atigh

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Androgenic alopecia (AGA) is a common form of hair loss, impacting approximately 50% of females, which leads to reduced self-esteem and quality of life. It causes progressive follicular miniaturization in genetically predisposed individuals. Mesotherapy -- a minimally invasive procedure, topical 2% minoxidil, and oral finasteride have emerged as popular treatment options in the realm of cosmetics. However, the efficacy of mesotherapy compared to other options remains unclear. This study aims to assess the effectiveness of mesotherapy when it is added to topical 2% minoxidil treatment on female androgenic alopecia. Mesotherapy, also known as intradermotherapy, is a technique that entails administering multiple intradermal injections of a carefully composed mixture of compounds in low doses, applied at various points in close proximity to or directly over the affected areas. This study involves a randomized controlled trial with 100 female participants diagnosed with androgenic alopecia. The subjects were randomly assigned to two groups: Group A used topical 2% minoxidil twice daily and took Finastride oral tablet. For Group B, 10 mesotherapy sessions were added to the prior treatment. The injections were administered every week in the first month of treatment, every two weeks in the second month, and after that the injections were applied monthly for four consecutive months. The response assessment was made at baseline, the 4th session, and finally after 6 months when the treatment was complete. Clinical photographs, 7-point Likert scale patient self-evaluation, and 7-point Likert scale assessment tool were used to measure the effectiveness of the treatment. During this evaluation, a significant and visible improvement in hair density and thickness was observed. The study demonstrated a significant increase in treatment efficacy in Group B compared to Group A post-treatment, with no adverse effects. Based on the findings, it appears that mesotherapy offers a significant improvement in female AGA over minoxidil. Hair loss was stopped in Group B after one month and improvement in density and thickness of hair was observed after the third month. The findings from this study provide valuable insights into the efficacy of mesotherapy in treating female androgenic alopecia. Our evaluation offers a detailed assessment of hair growth parameters, enabling a better understanding of the treatments' effectiveness. The potential of this promising technique is significantly enhanced when carried out in a medical facility, guided by appropriate indications and skillful execution. An interesting observation in our study is that in areas where the hair had turned grey, the newly regrown hair does not retain its original grey color; instead, it becomes darker. The results contribute to evidence-based decision-making in dermatological practice and offer different insights into the treatment of female pattern hair loss.

Keywords: androgenic alopecia, female hair loss, mesotherapy, topical 2% minoxidil

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Authors: Othman E. Othman, Agnés Germot, Daniel Petit, Abderrahman Maftah

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Threats to the biodiversity are increasing due to the loss of genetic diversity within the species utilized in agriculture. Due to the progressive substitution of the less productive, locally adapted and native breeds by highly productive breeds, the number of threatened breeds is increased. In these conditions, it is more strategically important than ever to preserve as much the farm animal diversity as possible, to ensure a prompt and proper response to the needs of future generations. Mitochondrial (mtDNA) sequencing has been used to explain the origins of many modern domestic livestock species. Studies based on sequencing of sheep mitochondrial DNA showed that there are five maternal lineages in the world for domestic sheep breeds; A, B, C, D and E. Because of the eastern location of Egypt in the Mediterranean basin and the presence of fat-tailed sheep breeds- character quite common in Turkey and Syria- where genotypes that seem quite primitive, the phylogenetic studies of Egyptian sheep breeds become particularly attractive. We aimed in this work to clarify the genetic affinities, biodiversity and phylogeny of five Egyptian sheep breeds using cytochrome B sequencing. Blood samples were collected from 63 animals belonging to the five tested breeds; Barki, Rahmani, Ossimi, Saidi and Sohagi. The total DNA was extracted and the specific primer allowed the conventional PCR amplification of the cytochrome B region of mtDNA (approximately 1272 bp). PCR amplified products were purified and sequenced. The alignment of Sixty-three samples was done using BioEdit software. DnaSP 5.00 software was used to identify the sequence variation and polymorphic sites in the aligned sequences. The result showed that the presence of 34 polymorphic sites leading to the formation of 18 haplotypes. The haplotype diversity in five tested breeds ranged from 0.676 in Rahmani breed to 0.894 in Sohagi breed. The genetic distances (D) and the average number of pairwise differences (Dxy) between breeds were estimated. The lowest distance was observed between Rahmani and Saidi (D: 1.674 and Dxy: 0.00150) while the highest distance was observed between Ossimi and Sohagi (D: 5.233 and Dxy: 0.00475). Neighbour-joining (Phylogeny) tree was constructed using Mega 5.0 software. The sequences of the 63 analyzed samples were aligned with references sequences of different haplogroups. The phylogeny result showed the presence of three haplogroups (HapA, HapB and HapC) in the 63 examined samples. The other two haplogroups described in literature (HapD and HapE) were not found. The result showed that 50 out of 63 tested animals cluster with haplogroup B (79.37%) whereas 7 tested animals cluster with haplogroup A (11.11%) and 6 animals cluster with haplogroup C (9.52%). In conclusion, the phylogenetic reconstructions showed that the majority of Egyptian sheep breeds belonging to haplogroup B which is the dominant haplogroup in Eastern Mediterranean countries like Syria and Turkey. Some individuals are belonging to haplogroups A and C, suggesting that the crosses were done with other breeds for characteristic selection for growth and wool quality.

Keywords: cytochrome B, diversity, phylogheny, Egyptian sheep breeds

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Authors: J. H. Boonzaaier, A. C. Brent

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South Africa, a water scarce country, experiences the phenomenon that its life supporting natural water resources is seriously threatened by the users that are totally dependent on it. South Africa is globally applauded to have of the best and most progressive water laws and policies. There are however growing concerns regarding natural water resource quality deterioration and a critical void in the management of natural resources and compliance to policies due to increasing institutional uncertainties and failures. These are in accordance with concerns of many South African researchers and practitioners that call for a change in paradigm from talk to practice and a more constructive, practical approach to governance challenges in the management of water resources. A qualitative theory-building case study through longitudinal action research was conducted from 2014 to 2017. The research assessed whether a strategic positioned institutional agent can be parlayed to facilitate and execute WRM on catchment level by engaging multiple stakeholders in a polycentric setting. Through a critical realist approach a distinction was made between ex ante self-deterministic human behaviour in the realist realm, and ex post governance-management in the constructivist realm. A congruence analysis, including Toulmin’s method of argumentation analysis, was utilised. The study evaluated the unique case of a self-steering local water management institution, the Impala Water Users Association (WUA) in the Pongola River catchment in the northern part of the KwaZulu-Natal Province of South Africa. Exploiting prevailing water resource threats, it expanded its ancillary functions from 20,000 to 300,000 ha. Embarking on WRM activities, it addressed natural water system quality assessments, social awareness, knowledge support, and threats, such as: soil erosion, waste and effluent into water systems, coal mining, and water security dimensions; through structured engagement with 21 different catchment stakeholders. By implementing a proposed polycentric governance-management model on a catchment scale, the WUA achieved to fill the void. It developed a foundation and capacity to protect the resilience of the natural environment that is critical for freshwater resources to ensure long-term water security of the Pongola River basin. Further work is recommended on appropriate statutory delegations, mechanisms of sustainable funding, sufficient penetration of knowledge to local levels to catalyse behaviour change, incentivised support from professionals, back-to-back expansion of WUAs to alleviate scale and cost burdens, and the creation of catchment data monitoring and compilation centres.

Keywords: institutional agent, water governance, polycentric water resource management, water resource management

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Authors: Tashwill Esterhuizen

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Throughout Africa, several countries continue to have laws which criminalise same-sex sexual activities, which increases the vulnerability of the LGBT community to stigma, discrimination, and persecution. These criminal provisions often form the basis upon which states deny LGBT activists the right to freely associate with other like-minded individuals and form organizations that protect their interests and advocate for the rights and aspirations of the LGBT community. Over the past year, however, there has been significant progress in the advancement of universal, fundamental rights of LGBT persons throughout Africa. In many instances, these advancements came about through the bravery of activists who have publically insisted (in environments where same-sex sexual practices are criminalised) that their rights should be respected. Where meaningful engagement with the State was fruitless, activists took their plight to the judiciary and have successfully sought to uphold the fundamental rights of LGBT persons, paving the way for a more inclusive and tolerant society. Litigation Progress: Botswana is a prime example. For several years, the State denied a group of LGBT activists their right to freely associate and form their organisation Lesbians, Gays, and Bisexuals of Botswana (LEGABIBO), which aimed to promote the interests of the LGBT community in Botswana. In March 2016, the Botswana Court of Appeal found that the government’s refusal to register LEGABIBO violated the activists’ right to associate freely. The Court held that the right freedom of association applies to all persons regardless of their sexual orientation or gender identity. It does not matter that the views of the organisation are unpopular or unacceptable amongst the majority. In particular, the Court rejected the government of Botswana’s contention that registering LEGABIBO would disturb public peace and is contrary to public morality. Quite remarkably, the Court of Appeal recognised that while LGBT individuals are a minority group within the country, they are nonetheless persons entitled to constitutional protections of their dignity, regardless of whether they are unacceptable to others on religious or any other grounds. Furthermore, the Court held that human rights and fundamental freedoms are granted to all, including criminals or social outcasts because the denial of an individual’s humanity is the denial of their human dignity. This is crucial observation by the Court of Appeal, as once it is accepted that human rights apply to all human beings, then it becomes much easier for vulnerable groups to assert their own rights. Conclusion: The Botswana Court of Appeal decision, therefore, represents significant progress in the promotion of the rights of lesbian, gay, bisexual and transgender persons. The judgment has broader implications for many other countries which do not provide recognition of sexual minorities. It highlights the State’s duty to uphold basic rights and to ensure dignity, tolerance, and acceptance for marginalised persons.

Keywords: acceptance, freedom of association, freedom of expression, fundamental rights and freedoms, gender identity, human rights are universal, inclusive, inherent human dignity, progress, sexual orientation, tolerance

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Tristan R. Fraser, Christopher D. Steadman, Christopher J. Boos

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Myopericarditis is an inflammation syndrome characterised by clinical diagnostic criteria for pericarditis, such as chest pain, combined with evidence of myocardial involvement, such as elevation of biomarkers of myocardial damage, e.g., troponins. It can rarely be a complication of therapeutics used for dysregulated immune-mediated diseases such as inflammatory bowel disease (IBD), for example, mesalazine. The infrequency of mesalazine-induced myopericarditis adds to the challenge in its recognition. Rapid diagnosis and the early introduction of treatment are crucial. This case report follows a 24-year-old professional footballer with a past medical history of ulcerative colitis, recently started on mesalazine for disease control. Three weeks after mesalazine was initiated, he was admitted with fever, shortness of breath, and chest pain worse whilst supine and on deep inspiration, as well as elevated venous blood cardiac troponin T level (cTnT, 288ng/L; normal: <13ng/L). Myocarditis was confirmed on initial inpatient cardiac MRI, revealing the presence of florid myocarditis with preserved left ventricular systolic function and an ejection fraction of 67%. This was a longitudinal case study following the progress of a single individual with myopericarditis over four acute hospital admissions over nine weeks, with admissions ranging from two to five days. Parameters examined included clinical signs and symptoms, serum troponin, transthoracic echocardiogram, and cardiac MRI. Serial measurements of cardiac function, including cardiac MRI and transthoracic echocardiogram, showed progressive deterioration of cardiac function whilst mesalazine was continued. Prior to cessation of mesalazine, transthoracic echocardiography revealed a small global pericardial effusion of < 1cm and worsening left ventricular systolic function with an ejection fraction of 45%. After recognition of mesalazine as a potential cause and consequent cessation of the drug, symptoms resolved, with cardiac MRI performed as an outpatient showing resolution of myocardial oedema. The patient plans to make a return to competitive sport. Patients suffering from myopericarditis are advised to refrain from competitive sport for at least six months in order to reduce the risk of cardiac remodelling and sudden cardiac death. Additional considerations must be taken in individuals for whom competitive sport is an essential component of their livelihood, such as professional athletes. Myopericarditis is an uncommon, however potentially serious medical condition with a wide variety of aetiologies, including viral, autoimmune, and drug-related causes. Management is mainly supportive and relies on prompt recognition and removal of the aetiological process. Mesalazine-induced myopericarditis is a rare condition; as such increasing awareness of mesalazine as a precipitant of myopericarditis is vital for optimising the management of these patients.

Keywords: myopericarditis, mesalazine, inflammatory bowel disease, professional athlete

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Authors: Anitha Muralidhara, Victor Engelen, Christophe Len, Pascal Pandard, Guy Marlair

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Production of bio-based chemicals and materials from lignocellulosic biomass is gaining tremendous importance in advanced bio-refineries while aiming towards progressive replacement of petroleum based chemicals in transportation fuels and commodity polymers. One such attempt has resulted in the production of key furan derivatives (FD) such as furfural, HMF, MMF etc., via acid catalyzed dehydration (ACD) of C6 and C5 sugars, which are further converted into key chemicals or intermediates (such as Furandicarboxylic acid, Furfuryl alcohol etc.,). In subsequent processes, many high potential FD are produced, that can be converted into high added value polymers or high energy density biofuels. During ACD, an unavoidable polyfuranic byproduct is generated which is called humins. The family of FD is very large with varying chemical structures and diverse physicochemical properties. Accordingly, the associated risk profiles may largely vary. Hazardous Material (Haz-mat) classification systems such as GHS (CLP in the EU) and the UN TDG Model Regulations for transport of dangerous goods are one of the preliminary requirements for all chemicals for their appropriate classification, labelling, packaging, safe storage, and transportation. Considering the growing application routes of FD, it becomes important to notice the limited access to safety related information (safety data sheets available only for famous compounds such as HMF, furfural etc.,) in these internationally recognized haz-mat classification systems. However, these classifications do not necessarily provide information about the extent of risk involved when the chemical is used in any specific application. Factors such as thermal stability, speed of combustion, chemical incompatibilities, etc., can equally influence the safety profile of a compound, that are clearly out of the scope of any haz-mat classification system. Irrespective of the bio-based origin, FD has so far received inconsistent remarks concerning their toxicity profiles. With such inconsistencies, there is a fear that, a large family of FD may also follow extreme judgmental scenarios like ionic liquids, by ranking some compounds as extremely thermally stable, non-flammable, etc., Unless clarified, these messages could lead to misleading judgements while ranking the chemical based on its hazard rating. Safety is a key aspect in any sustainable biorefinery operation/facility, which is often underscored or neglected. To fill up these existing data gaps and to address ambiguities and discrepancies, the current study focuses on giving preliminary insights on safety assessment of FD and their potential targeted by-products. With the available information in the literature and obtained experimental results, physicochemical safety, environmental safety as well as (a scenario based) fire safety profiles of key FD, as well as side streams such as humins and levulinic acid, will be considered. With this, the study focuses on defining patterns and trends that gives coherent safety related information for existing and newly synthesized FD in the market for better functionality and sustainable applications.

Keywords: furanics, humins, safety, thermal and fire hazard, toxicity

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Authors: Valeria Cotza

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School drop-out is a multifactorial phenomenon that in Italy concerns all those underage students who, at different school stages (up to 16 years old) or training (up to 18 years old), manifest educational difficulties from dropping out of compulsory education without obtaining a qualification to repetition rates and absenteeism. From the 1980s to the 2000s, there was a progressive attenuation of the economic and social model towards a multifactorial reading of the phenomenon, and the European Commission noted the importance of learning about the phenomenon through approaches able to integrate large-scale quantitative surveys with qualitative analyses. It is not a matter of identifying the contextual factors affecting the phenomenon but problematising them by means of systemic and comprehensive in-depth analysis. So, a privileged point of observation and field of intervention are those schools that propose alternative models of teaching and learning to the traditional ones, such as popular and second-chance schools. Alternative schools and interventions grew in these years in Europe as well as in the US and Latin America, working in the direction of greater equity to create the conditions (often absent in conventional schools) for everyone to achieve educational goals. Against extensive Anglo-Saxon and US literature on this topic, there is yet no unambiguous definition of alternative education, especially in Europe, where second-chance education has been most studied. There is little literature on a second chance in Italy and almost none on alternative education (with the exception of method schools, to which in Italy the concept of “alternative” is linked). This research aims to fill the gap by systematically surveying the alternative interventions in the area and beginning to explore some models of popular and second-chance schools and experiences through a mixed methods approach. So, the main research objectives concern the spread of alternative education in the Lombardy region, the main characteristics of these schools and interventions, and their effectiveness in terms of students’ well-being and school results. This paper seeks to answer the first point by presenting the preliminary results of the first phase of the project dedicated to mapping. Through the Google Forms platform, a questionnaire is being distributed to all schools in Lombardy and some schools in the rest of Italy to map the presence of alternative schools and interventions and their main characteristics. The distribution is also taking place thanks to the support of the Milan Territorial and Lombardy Regional School Offices. Moreover, other social realities outside the school system (such as cooperatives and cultural associations) can be questioned. The schools and other realities to be questioned outside Lombardy will also be identified with the support of INDIRE (Istituto Nazionale per Documentazione, Innovazione e Ricerca Educativa, “National Institute for Documentation, Innovation and Educational Research”) and based on existing literature and the indicators of “Futura” Plan of the PNRR (Piano Nazionale di Ripresa e Resilienza, “National Recovery and Resilience Plan”). Mapping will be crucial and functional for the subsequent qualitative and quantitative phase, which will make use of statistical analysis and constructivist grounded theory.

Keywords: school drop-out, alternative education, popular and second-chance schools, map

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Authors: Nikitha Francis, Anjana Hoode, Vinitha George, Jayashree S. Bhat

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The interaction between cognition and language, referred as cognitive-communication, is very intricate, involving several mental processes such as perception, memory, attention, lexical retrieval, decision making, motor planning, self-monitoring and knowledge. Cognitive-communication disorders are difficulties in communicative competencies that result from underlying cognitive impairments of attention, memory, organization, information processing, problem solving, and executive functions. Traumatic brain injury (TBI) is an acquired, non - progressive condition, resulting in distinct deficits of cognitive communication abilities such as naming, word-finding, self-monitoring, auditory recognition, attention, perception and memory. Cognitive-communication intervention in TBI is individualized, in order to enhance the person’s ability to process and interpret information for better functioning in their family and community life. The present case report illustrates the cognitive-communicative behaviors and the intervention outcomes of an adult with TBI, who was brought to the Department of Audiology and Speech Language Pathology, with cognitive and communicative disturbances, consequent to road traffic accident. On a detailed assessment, she showed naming deficits along with perseverations and had severe difficulty in recalling the details of the accident, her house address, places she had visited earlier, names of people known to her, as well as the activities she did each day, leading to severe breakdowns in her communicative abilities. She had difficulty in initiating, maintaining and following a conversation. She also lacked orientation to time and place. On administration of the Manipal Manual of Cognitive Linguistic Abilities (MMCLA), she exhibited poor performance on tasks related to visual and auditory perception, short term memory, working memory and executive functions. She attended 20 sessions of cognitive-communication intervention which followed a domain-general, adaptive training paradigm, with tasks relevant to everyday cognitive-communication skills. Compensatory strategies such as maintaining a dairy with reminders of her daily routine, names of people, date, time and place was also recommended. MMCLA was re-administered and her performance in the tasks showed significant improvements. Occurrence of perseverations and word retrieval difficulties reduced. She developed interests to initiate her day-to-day activities at home independently, as well as involve herself in conversations with her family members. Though she lacked awareness about her deficits, she actively involved herself in all the therapy activities. Rehabilitation of moderate to severe head injury patients can be done effectively through a holistic cognitive retraining with a focus on different cognitive-linguistic domains. Selection of goals and activities should have relevance to the functional needs of each individual with TBI, as highlighted in the present case report.

Keywords: cognitive-communication, executive functions, memory, traumatic brain injury

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Authors: Mathula Thangarajh

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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

Procedia PDF Downloads 74

Authors: Lindsey D. Sams, Dean R. Gorman, Cathy D. Lirgg, Steve W. Dittmore, Jack C. Kern

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Golf is a lifetime sport that provides numerous physical and psychological benefits. The game has struggled with attrition and retention within minority groups and this has exposed the lack of a modified introduction to the game that is uniformly accessible and developmentally appropriate. Factors that have been related to sport participatory behaviors include perceived competence, enjoyment and intention. The purpose of this study was to examine self-reported perception differences in competence and enjoyment between learners using modified and traditional equipment as well as the potential effects these factors could have on intent for future participation. For this study, SNAG Golf was chosen to serve as the scaled equipment used by the modified equipment group. The participants in this study were 99 children (24 traditional equipment users/ 75 modified equipment users) located across the U.S. with ages ranging from 7 to 12 years (2nd-5th grade). Utilizing a convenience sampling method, data was obtained on a voluntary basis through surveys measuring children’s golf participation and self-perceptions concerning perceived competence, enjoyment and intention to continue participation. The scales used for perceived competence and enjoyment included Susan Harter’s Self-Perception Profile for Children (SPPC) along with the Physical Activity Enjoyment Scale (PACES). Analysis revealed no significant differences for enjoyment, perceived competence or intention between children learning with traditional golf equipment and modified golf equipment. This was true even though traditional equipment users reported significantly higher experience levels than that of modified users. Intention was regressed on the enjoyment and perceived competence variables. Congruent with current literature, enjoyment was a strong predictor of intention to continue participation, for both groups. Modified equipment users demonstrated significantly lower experience levels but reported similar levels of competence, enjoyment and intent to continue participation as reported by the more experienced, and potentially more skilled, traditional users. The ability to immediately generate these positive affects suggests the potential adoption of a more effective way to learn golf and a method that is conducive to participatory behaviors related to attrition and retention. These implications in turn, highlight an equipment candidate ideal for inception into physical education programs where new learners are introduced to various sports in safe and developmentally appropriate environments. A major goal of this study was to provide foundational research that instigates the further examination of golf’s introductory teaching methodologies, as there is a lack of its presence in current literature. Future research recommendations range from improvements in the current research design to expansive approaches related to the topic, such as progressive skill development, knowledge of the game’s tactical and strategic concepts, playing ability and teaching effectiveness when utilizing modified versus traditional equipment.

Keywords: adaptive sports, enjoyment, golf participation, modified equipment, perceived competence, SNAG golf

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Authors: Akintade O. Adeboyejo, Edwin O. Clarke, Oluwatoyin Aderinola

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The present study is on the sub-lethal toxicity of industrial effluents (IE) from the environment of Ologe Lagoon, Lagos, Nigeria on the African catfish fingerlings Clarias gariepinus. The fish were cultured in varying concentrations of industrial effluents: 0% (control), 5%, 15%, 25%, and 35%. Trials were carried out in triplicates for twelve (12) weeks. The culture system was a static renewable bioassay and was carried out in the fisheries laboratory of the Lagos State University, Ojo-Lagos. Weekly physico-chemical parameters: Temperature (0C), pH, Conductivity (ppm) and Dissolved Oxygen (DO in mg/l) were measured in each treatment tank. Length (cm) and weight (g) data were obtained weekly and used to calculate various growth parameters: mean weight gain (MWG), percentage weight gain (PWG), daily weight gain (DWG), specific growth rate (SGR) and survival. Haematological (Packed Cell Volume (PCV), Red blood cells (RBC), White Blood Cell (WBC), Neutrophil and Lymphocytes etc) and histological alterations were measured after 12 weeks. The physico-chemical parameters showed that the pH ranged from 7.82±0.25–8.07±0.02. DO range from 1.92±0.66-4.43±1.24 mg/l. The conductivity values increased with increase in concentration of I.E. While the temperature remained stable with mean value range between 26.08±2.14–26.38±2.28. The DO showed significant differences at P<0.05. There was progressive increase in length and weight of fish during the culture period. The fish placed in the control had highest increase in both weight and length while fish in 35% had the least. MWG ranged from 16.59–35.96, DWG is from 0.3–0.48, SGR varied from 1.0–1.86 and survival was 100%. Haematological results showed that C. gariepinus had PCV ranging from 13.0±1.7-27.7±0.6, RBC ranged from 4.7±0.6–9.1±0.1, and Neutrophil ranged from 26.7±4.6–61.0±1.0 amongst others. The highest values of these parameters were obtained in the control and lowest at 35%. While the reverse effects were observed for WBC and lymphocytes. This study has shown that effluents may affect the health status of the test organism and impair vital processes if exposure continues for a long period of time. The histological examination revealed several lesions as expressed by the gills and livers. The histopathology of the gills in the control tanks had normal tissues with no visible lesion, but at higher concentrations, there were: lifting of epithelium, swollen lamellae and gill arch infiltration, necrosis and gill arch destruction. While in the liver: control (0%) show normal liver cells, at higher toxic level, there were: vacoulation, destruction of the hepatic parenchyma, tissue becoming eosinophilic (i.e. tending towards Carcinogenicity) and severe disruption of the hepatic cord architecture. The study has shown that industrial effluents from the study area may affect fish health status and impair vital processes if exposure continues for a long period of time even at lower concentrations (Sublethal).

Keywords: sublethal toxicity, industrial effluents, clarias gariepinus, ologe lagoon

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Angela Oktavia Suryani, Bernadeth Gloria, Edwin Sutamto, Jessica Kristianty, Ni Made Rai Sapitri, Patricia Catherine Agla, Sitti Arlinda Rochiadi

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It was found that some blogs or personal websites in Indonesia sell standardized intelligence tests (for example, Progressive Matrices (PM), Intelligence Structure Test (IST), and Culture Fair Intelligence Test (CFIT)) and other psychological tests, together with the manual and the key answers for public. Individuals can buy and prepare themselves for selection or recruitment with the real test. This action drives people to lie to the institution (education or company) and also to themselves. It was also found that those tests are old. Some items are not relevant with the current context, for example a question about a diameter of a certain coin that does not exist anymore. These problems motivate us to develop a new intelligence battery test, namely of Multiple Aptitude Battery (MAB). The battery test was built by using Thurstone’s Primary Mental Abilities theory and intended to be used by high schools students, university students, and worker applicants. The battery tests consist of 9 subtests. In the current study we examine six subtests, namely Reading Comprehension, Verbal Analogies, Numerical Inductive Reasoning, Numerical Deductive Reasoning, Mechanical Ability, and Two Dimensional Spatial Reasoning for university students. The study included 1424 data from students recruited by convenience sampling from eight faculties at Atma Jaya Catholic University of Indonesia. Classical and modern test approaches (Item Response Theory) were carried out to identify the item difficulties of the items and confirmatory factor analysis was applied to examine their internal validities. The validity of each subtest was inspected by using convergent–discriminant method, whereas the reliability was examined by implementing Kuder–Richardson formula. The result showed that the majority of the subtests were difficult in medium level, and there was only one subtest categorized as easy, namely Verbal Analogies. The items were found homogenous and valid measuring their constructs; however at the level of subtests, the construct validity examined by convergent-discriminant method indicated that the subtests were not unidimensional. It means they were not only measuring their own constructs but also other construct. Three of the subtests were able to predict academic performance with small effect size, namely Reading Comprehension, Numerical Inductive Reasoning, and Two Dimensional Spatial Reasoning. GPAs in intermediate level (GPAs at third semester and above) were considered as a factor for predictive invalidity. The Kuder-Richardson formula showed that the reliability coefficients for both numerical reasoning subtests and spatial reasoning were superior, in the range 0.84 – 0.87, whereas the reliability coefficient for the other three subtests were relatively below standard for ability test, in the range of 0.65 – 0.71. It can be concluded that some of the subtests are ready to be used, whereas some others are still need some revisions. This study also demonstrated that the convergent-discrimination method is useful to identify the general intelligence of human.

Keywords: intelligence, psychometric examination, multiple aptitude battery, university students

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Authors: Z. M. T. Lim, W. Q. Yow

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Diversity in individual problem-solving approaches, culture and nationality have been shown to have positive effects on collaborative creative processes in organizational and scholastic settings. For example, diverse graduate and organizational teams consisting of members with both structured and unstructured problem-solving styles were found to have more creative ideas on a collaborative idea generation task than teams that comprised solely of members with either structured or unstructured problem-solving styles. However, being different may not always provide benefits to the collaborative creative process. In particular, speaking different languages may hinder mutual engagement through impaired communication and thus collaboration. Instead, sharing similar languages may have facilitative effects on mutual engagement in collaborative tasks. However, no studies have explored the relations between language diversity and adults’ collaborative creative problem solving. Sixty-four Singaporean English-speaking bilingual undergraduates were paired up into similar or dissimilar language pairs based on the second language they spoke (e.g., for similar language pairs, both participants spoke English-Mandarin; for dissimilar language pairs, one participant spoke English-Mandarin and the other spoke English-Korean). Each participant completed the Ravens Progressive Matrices Task individually. Next, they worked in pairs to complete a collaborative divergent thinking task where they used mind-mapping techniques to brainstorm ideas on a given problem together (e.g., how to keep insects out of the house). Lastly, the pairs worked on a collaborative insight problem-solving task (Triangle of Coins puzzle) where they needed to flip a triangle of ten coins around by moving only three coins. Pairs who had prior knowledge of the Triangle of Coins puzzle were asked to complete an equivalent Matchstick task instead, where they needed to make seven squares by moving only two matchsticks based on a given array of matchsticks. Results showed that, after controlling for intelligence, similar language pairs completed the collaborative insight problem-solving task faster than dissimilar language pairs. Intelligence also moderated these relations. Among adults of lower intelligence, similar language pairs solved the insight problem-solving task faster than dissimilar language pairs. These differences in speed were not found in adults with higher intelligence. No differences were found in the number of ideas generated in the collaborative divergent thinking task between similar language and dissimilar language pairs. In conclusion, sharing similar languages seem to enrich collaborative creative processes. These effects were especially pertinent to pairs with lower intelligence. This provides guidelines for the formation of groups based on shared languages in collaborative creative processes. However, the positive effects of shared languages appear to be limited to the insight problem-solving task and not the divergent thinking task. This could be due to the facilitative effects of other factors of diversity as found in previous literature. Background diversity, for example, may have a larger facilitative effect on the divergent thinking task as compared to the insight problem-solving task due to the varied experiences individuals bring to the task. In conclusion, this study contributes to the understanding of the effects of language diversity in collaborative creative processes and challenges the general positive effects that diversity has on these processes.

Keywords: bilingualism, diversity, creativity, collaboration

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Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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Authors: M. Testa, L. Peotta, S. Giusiano, B. Lazzolino, U. Manera, A. Canosa, M. Grassano, F. Palumbo, A. Bombaci, S. Cabras, F. Di Pede, L. Solero, E. Matteoni, C. Moglia, A. Calvo, A. Chio

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Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of adulthood, which primarily affects the central nervous system and is characterized by progressive bilateral degeneration of motor neurons. The degeneration processes in ALS extend far beyond the neurons of the motor system, and affects cognition, behaviour and language. To outline the prevalence of language deficits in an ALS cohort and explore their profile along with demographic and neuropsychological data. A full neuropsychological battery and language assessment was administered to 56 ALS patients. Neuropsychological assessment included tests of executive functioning, verbal fluency, social cognition and memory. Language was assessed using tests for verbal comprehension, production and pragmatics. Patients were cognitively classified following the Revised Consensus Criteria and divided in three groups showing different levels of language deficits: group 1 - no language deficit; group 2 - one language deficit; group 3 - two or more language deficits. Chi-square for independence and non-parametric measures to compare groups were applied. Nearly half of ALS-CN patients (48%) reported one language test under the clinical cut-off, and only 13% of patents classified as ALS-CI showed no language deficits, while the rest 87% of ALS-CI reported two or more language deficits. ALS-BI and ALS-CBI cases all reported two or more language deficits. Deficits in production and in comprehension appeared more frequent in ALS-CI patients (p=0.011, p=0.003 respectively), with a higher percentage of comprehension deficits (83%). Nearly all ALS-CI reported at least one deficit in pragmatic abilities (96%) and all ALS-BI and ALS-CBI patients showed pragmatic deficits. Males showed higher percentage of pragmatic deficits (97%, p=0.007). No significant differences in language deficits have been found between bulbar and spinal onset. Months from onset and level of impairment at testing (ALS-FRS total score) were not significantly different between levels and type of language impairment. Age and education were significantly higher for cases showing no deficits in comprehension and pragmatics and in the group showing no language deficits. Comparing performances at neuropsychological tests among the three levels of language deficits, no significant differences in neuropsychological performances were found between group 1 and 2; compared to group 1, group 3 appeared to decay specifically on executive testing, verbal/visuospatial learning, and social cognition. Compared to group 2, group 3 showed worse performances specifically in tests of working memory and attention. Language deficits have found to be spread in our sample, encompassing verbal comprehension, production and pragmatics. Our study reveals that also cognitive intact patients (ALS-CN) showed at least one language deficit in 48% of cases. Pragmatic domain is the most compromised (84% of the total sample), present in nearly all ALS-CI (96%), likely due to the influence of executive impairment. Lower age and higher education seem to preserve comprehension, pragmatics and presence of language deficits. Finally, executive functions, verbal/visuospatial learning and social cognition differentiate the group with no language deficits from the group with a clinical language impairment (group 3), while attention and working memory differentiate the group with one language deficit from the clinical impaired group.

Keywords: amyotrophic lateral sclerosis, language assessment, neuropsychological assessment, language deficit

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Authors: Ekemini M. Okon, Reuben C. Okocha, Babatunde T. Adesina, Judith O. Ehigie, Babatunde M. Falana, Boluwape T. Okikiola

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Antimicrobial resistance (AMR) has evolved to become a significant threat to global public health and food safety. The development of AMR in animals has been associated with antimicrobial overuse. In recent years, the number of antimicrobials used in food animals such as fish and poultry has escalated. It, therefore, becomes imperative to understand the patterns of AMR in fish and poultry and map out future directions for better surveillance efforts. This study used the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA) to assess the trend, patterns, and spatial distribution for AMR research in Egypt, Nigeria, and South Africa. A literature search was conducted through the Scopus and Web of Science databases in which published studies on AMR between 1989 and 2021 were assessed. A total of 172 articles were relevant for this study. The result showed progressive attention on AMR studies in fish and poultry from 2018 to 2021 across the selected countries. The period between 2018 (23 studies) and 2021 (25 studies) showed a significant increase in AMR publications with a peak in 2019 (28 studies). Egypt was the leading exponent of AMR research (43%, n=74) followed by Nigeria (40%, n=69), then South Africa (17%, n=29). AMR studies in fish received relatively little attention across countries. The majority of the AMR studies were on poultry in Egypt (82%, n=61), Nigeria (87%, n=60), and South Africa (83%, n=24). Further, most of the studies were on Escherichia and Salmonella species. Antimicrobials frequently researched were ampicillin, erythromycin, tetracycline, trimethoprim, chloramphenicol, and sulfamethoxazole groups. Multiple drug resistance was prevalent, as demonstrated by antimicrobial resistance patterns. In poultry, Escherichia coli isolates were resistant to cefotaxime, streptomycin, chloramphenicol, enrofloxacin, gentamycin, ciprofloxacin, oxytetracycline, kanamycin, nalidixic acid, tetracycline, trimethoprim/sulphamethoxazole, erythromycin, and ampicillin. Salmonella enterica serovars were resistant to tetracycline, trimethoprim/sulphamethoxazole, cefotaxime, and ampicillin. Staphylococcusaureus showed high-level resistance to streptomycin, kanamycin, erythromycin, cefoxitin, trimethoprim, vancomycin, ampicillin, and tetracycline. Campylobacter isolates were resistant to ceftriaxone, erythromycin, ciprofloxacin, tetracycline, and nalidixic acid at varying degrees. In fish, Enterococcus isolates showed resistance to penicillin, ampicillin, chloramphenicol, vancomycin, and tetracycline but sensitive to ciprofloxacin, erythromycin, and rifampicin. Isolated strains of Vibrio species showed sensitivity to florfenicol and ciprofloxacin, butresistance to trimethoprim/sulphamethoxazole and erythromycin. Isolates of Aeromonas and Pseudomonas species exhibited resistance to ampicillin and amoxicillin. Specifically, Aeromonashydrophila isolates showed sensitivity to cephradine, doxycycline, erythromycin, and florfenicol. However, resistance was also exhibited against augmentinandtetracycline. The findings constitute public and environmental health threats and suggest the need to promote and advance AMR research in other countries, particularly those on the global hotspot for antimicrobial use.

Keywords: antibiotics, antimicrobial resistance, bacteria, environment, public health

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Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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