Search results for: oral keratinocyte

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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Authors: Nataliya G. Olkhovik

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Nowadays in the system of Russian higher medical education there have been undertaken initiatives that resulted in focusing on the resources of e-learning in teaching foreign languages. Obviously, the face-to-face communication in foreign languages bears much more advantages in terms of effectiveness in comparison with the potential of e-learning. Thus, we’ve faced the necessity of strengthening the capacity of e-learning via integration of active methods into the process of teaching foreign languages, such as project activity of students. Successful project activity of students should involve the following components: monitoring, control, methods of organizing the student’s activity in foreign languages, stimulating their interest in the chosen project, approaches to self-assessment and methods of raising their self-esteem. The contemporary methodology assumes the project as a specific method, which activates potential of a student’s cognitive function, emotional reaction, ability to work in the team, commitment, skills of cooperation and, consequently, their readiness to verbalize ideas, thoughts and attitudes. Verbal activity in the foreign language is a complex conception that consolidates both cognitive (involving speech) capacity and individual traits and attitudes such as initiative, empathy, devotion, responsibility etc. Once we organize the project activity by the means of e-learning within the ‘Foreign language’ discipline we have to take into consideration all mentioned above characteristics and work out an effective way to implement it into the teaching practice to boost its educational potential. We have integrated into the e-platform Moodle the module of project activity consisting of the following blocks of tasks that lead students to research, cooperate, strive to leadership, chase the goal and finally verbalize their intentions. Firstly, we introduce the project through activating self-activity of students by the tasks of the phase ‘Preparation of the project’: choose the topic and justify it; find out the problematic situation and its components; set the goals; create your team, choose the leader, distribute the roles in your team; make a written report on grounding the validity of your choices. Secondly, in the ‘Planning the project’ phase we ask students to represent the analysis of the problem in terms of reasons, ways and methods of solution and define the structure of their project (here students may choose oral or written presentation by drawing up the claim in the e-platform about their wish, whereas the teacher decides what form of presentation to prefer). Thirdly, the students have to design the visual aids, speech samples (functional phrases, introductory words, keywords, synonyms, opposites, attributive constructions) and then after checking, discussing and correcting with a teacher via the means of Moodle present it in front of the audience. And finally, we introduce the phase of self-reflection that aims to awake the inner desire of students to improve their verbal activity in a foreign language. As a result, by implementing the project activity into the e-platform and project activity, we try to widen the frameworks of a traditional lesson of foreign languages through tapping the potential of personal traits and attitudes of students.

Keywords: active methods, e-learning, improving verbal activity in foreign languages, personal traits and attitudes

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Authors: Amna B. Medani, M. A. Elbadwi Samia, Hassan A. Khalid

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In our study, nine Nubian goat kids were obtained, allotted into three groups, and healthily adapted in pens within the premises of the Veterinary Teaching Hospital, University of Khartoum to be given the oral doses of the dried herb shoots at daily doses of 1 and 5 gm/kg/day with drinking water, while the kids of the control group were left undosed. All goats were slaughtered,if not died, after 35 days. S. argel at the given doses caused signs of arched posture, ruffled hair, shivering and paralysis of limbs. On post mortem, lesions were seen to be hepatic fatty changes, renal necrosis, congested lungs and inflamed intestines. Serum chemistry investigations revealed significant increase (P< 0.05-0.01) in the activities of ALP(alkaline phosphates) and AST( aspartate-aminotransferase) in goats dosed with 5 gm /kg/ day. Also observed were significant increases in inorganic phosphorus and urea concentrations (P < 0.05-0.01) in both dosed goat groups. .Other investigations including the activity of GGT( gamma glutamyltransferase), creatinine, calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. On haematological evaluation , the goat kids dosed with 5 gm/kg/dayshowed a decrease in haemoglobin concentration and red blood cells count of (P < 0.05-0.01).Both groups of dosed goats showed a higher packed cell volume values of (P < 0.05) when compared to the control goats .Mean corpuscular haemoglobin values were not different from those of the control kids. S. argel at the given doses caused signs of arched posture, ruffled hair, shivering and paralysis of limbs. On post mortem, lesions were seen to be hepatic fatty changes, renal necrosis, congested lungs and inflamed intestines. Serum chemistry investigations revealed significant increase (P < 0.05-0.01) in the activities of ALP(alkaline phosphates) and AST( aspartate-aminotransferase) in goats dosed with 5 gm /kg/ day. Also observed were significant increases in inorganic phosphorus and urea concentrations (P < 0.05-0.01) in both dosed goat groups. .Other investigations including the activity of GGT( gamma-glutamyltransferase), creatinine, calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. On haematological evaluation , the goat kids dosed with 5 gm/kg/dayshowed a decrease in haemoglobin concentration and red blood cells count of (P < 0.05-0.01).Both groups of dosed goats showed a higher packed cell volume values of (P < 0.05) when compared to the control goats .Mean corpuscular haemoglobin values were not different from those of the control kids. Data obtained were then discussed to find S. argel irritable to intestines , toxic to the kidney and liver and a haematological mild toxin.Suggestions for future were forwarded.

Keywords: hargal, nubian goats, solenstemma argel, toxicity

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Authors: Yobo Opare-Addo

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Ghana came under a military and democratic rule of the same leadership from 1981-2000. These were the Provisional National Defense Council (PNDC), a military government and a democratic government, the National Democratic Congress (NDC) both under the leadership of Flt. Lt. J.J. Rawlings. Meanwhile the year 1985 marked a turning point in the development of the tourism industry in Ghana. Interest in tourism among African governments and for that matter the ‘PNDC cum NDC Government’ (PNDC/NDC) arose because of adverse developments in intangible exports and a corresponding decline in commodity export earnings. The ‘PNDC/NDC Government’ undertook measures and policies to improve the tourism industry and at the same time embarked on export diversification to reap the foreign exchange that the industry could generate in Ghana. The objective of this paper is to examine the measures and policies of the PNDC/NDC to improve the tourism industry in order to reap the foreign exchange. It specifically interrogates the role of the government as an agent of tourism development, through its deliberate creation of a conducive environment for tourism to flourish, the involvement of the private sector both foreign and local and the provision of tourism facilities and infrastructure and how these factors impacted on the tourism industry in Ghana. In the final analysis it evaluates the degree of success of the PNDC/NDC Government in this arena of Ghana’s socio-cultural and economic development. Introduction The Provisional National Defense Council (PNDC), a military government under the leadership of Flt. Lt J.J. Rawlings overthrew a constitutionally elected government of People’s National Party in 1981. In 1992, the National Democratic Congress (NDC) won the general election conducted in December. Flt. Lt. J.J. Rawlings, the party’s leader became the President of the Fourth Republic from January 1993 to December 2000. It was refreshing to see Ghanaians embrace democracy with renewed energy, zeal, and enthusiasm. This paper takes a critical look at the efforts of the PNDC cum NDC Government (PNDC/NDC) to develop tourism in Ghana during the period from 1981-2000 Methodology: Qualitative method of research was adopted for the study. Data was collected from both primary and secondary sources, and analysis was done using descriptive analysis because descriptive analysis made it possible to describe or summarize the statistical data in the research. To gather data from primary sources, questionnaires, oral interviews, and semi-structured discussions were conducted. Respondents included public officials from Ghana Tourist Board, Ministry of Tourism, Hoteliers, restaurant operators and travel and tour operators in Accra. Secondary data sources included articles in journals, reports, magazines, bulletins, and books. The major findings included statistical data for tourism arrivals and receipts during the period and the status of the industry by the year 2000. Conclusion: The paper contributes to knowledge on political and historical aspects of tourism development in Ghana, which is almost non-existent, attitudes of the PNDC cum NDC government towards tourism development and the debates on the generation of foreign exchange to Ghana and third world countries.

Keywords: ghana, infrastructure, policies, privatization, tourism facilities

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Authors: Ana Magana

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Youth are entering the juvenile justice system at alarming rates. For the youth of color entering the system, the outcomes are far worse than for their white counterparts. In fact, the youth of color are more likely to be arrested and sentenced for longer periods of time than white youth. Race disproportionality in the juvenile justice system is evident, but what happens to the youth that exit the juvenile justice system? Who supports them after they are incarcerated and who can prevent them from re-offending? There are several diversion programs that have been implemented in the US to aid the reduction of juvenile incarceration and help reduce recidivism. The program interviewed for this study is a community-based diversion program (CBDP). The CBDP is a pre-filing diversion non-profit organization based in South Seattle. The objective of this exploratory research study is to provide a space and platform for the CBDP team to speak about their background experiences and the influence their background has on their current approach and practice with juveniles. A qualitative, exploratory study was conducted. Interviews were conducted with staff and provided oral consent. The interview included six open-ended, semi-structured questions. Interviews were digitally recoded and transcribed. The aim of this study was to understand how the influence of the participant’s backgrounds and previous experiences impact their current practice approaches with the CBDP youth and young adults. Ecological systems theory was the guiding framework for analysis. After careful analysis, three major themes emerged: 1) strong influence of participant’s background, 2) participants belonging to community and 3) strong self-identity with the CBDP. Within these three themes, subthemes were developed based on participant’s responses. It was concluded that the participant’s approach is influenced by their background experiences. This corresponds to the ecological systems theory and the community-based lens which underscores theoretical analysis. The participant’s approach is grounded in interpersonal relationships within the client’s systems, meaning that the participants understand and view their clients within an ecological systems perspective. When choosing participants that reflect the population being served, the clients receive a balanced, inclusive and caring approach. Youth and young adults are searching for supportive adults to be there for them, it is essential for diversion programs to provide a space for shared background experiences and have people that hold similar identities. Grassroots organizations such as CBDP have the tools and experience to work with marginalized populations that are constantly being passed on. While articles and studies focus on the reduction of recidivism and re-offending it is important to question the reasons behind this data. For instance, there can be a reduction in statistics, but at whose expense. Are the youth and young adults truly being supported? Or is it just a requirement that they are completing in order to remove their charge? This research study can serve as the beginning of a series of studies conducted at CBDP to further understand and validate the need to employ individuals with similar backgrounds as the participants CBDP serves.

Keywords: background experience, diversion, ecological systems theory, relationships

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Authors: Abubakar Bello Usman, Alhassan Muhammad Gani, Kolo Ibrahim

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The use of botanical raw materials to produce pharmaceuticals, herbal remedies, teas, spirits, cosmetics, sweets, dietary supplements, special industrial compounds and crude materials constitute an important global resource in terms of healthcare and economy. In Nigeria and other developing countries, the indigenous knowledge on the uses of plants lies with the older generation and the traditional healers. However, these custodians are decreasing in number due to death and other unforeseen occurrences. An Ethno-botanical survey was carried out to obtain information on the ethno medical values of wide range of plants used by the people of Gombe State, North-Eastern Nigeria, in the practice of healing and cure of typhoid (enteric) fever. Oral interviews were conducted so as to consider those with low literacy level who are involved in the practice of traditional medicine and thirty four (34) informants availed themselves for the interview and were consulted. All relevant information obtained from the respondents was recorded. A recent and valid nomenclature, along with local names, family names, part of the plant(s) used, methods of preparation and administration and fifty four (54) plant species belonging to 27 families as well as 7 unidentified species that are commonly used by the people of the state in ethnomedical treatment of the ailment were tabulated. Those interviewed included traditional practitioners, local herb sellers, traditional rulers, hunters, farmers and patients. Specific questions were asked and information supplied by informants was promptly documented. Results showed that the people of Gombe State are knowledgeable on herbal medicine in the treatment of diseases and ailments. Furthermore, the aqueous leaf extracts of Senna siamea, the plant species with the highest PPK (percentage of people who have knowledge about the use of a species for treating typhoid fever) in this ethnobotanical survey, was tested for its activity against clinical isolates of Salmonella typhi using the agar well diffusion method. The aqueous extracts showed some activity (zones of inhibition 11, 9, 7.5, 3.5, 1.3 mm) at 2000, 1800, 1600, 1400, 1200 µg/ml concentrations respectively. Preliminary phytochemical studies of the aqueous leaf extracts of the plant revealed the presence of secondary metabolites such as alkaloids, saponins, tannins, flavonoids and cardiac glycosides. Though a large number of traditionally used plants for the treatment of enteric fever were identified, further scientific validation of the traditional claims of anti-typhoid properties is imperative. This would establish their candidature for any possible future research for active principles and the possible development of new cheaper and more effective anti-typhoid drugs, as well as in the conservation of this rich diversity of medicinal plants.

Keywords: antimicrobial activities, ethnobotany, gombe state, north-eastern Nigeria, phytochemical screening, senna siamea, typhoid fever

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Authors: Sanaa Riaz

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The free people, Amazigh (plural Imazighen), often known by the more popular exonym, Berber, are spread across several North African countries with the highest population in Morocco have been substantially misunderstood and differentially showcased by entities from western-school educated scholars to human, health and women’s rights organizations, to the State to the international community. This paper is an examination of the various conceptualization of the Imazighen. With the popularity of the Arab Spring movement to oust monarchical and dictatorial rulers across the Middle East and North Africa in Morocco, the Moroccan monarchy introduced various reform programs to win public favor. These included social, economic and educational reforms to incorporate marginalized groups such as the Imazighen. The monarchy has ushered Amazigh representation in public offices and landscape through Amazigh script, even though theirs has been an oral culture. After the Arab Spring, the Justice and Development party, an Islamist party took over in Morocco due to its accessibility to the masses, In Sept. 2021, unlike the case of Egypt and Tunisia where military and constitutional means were sought, Morocco successfully removed it from power through the ballot, resulting in a real victory for the neutral monarchy and its representation as a moderate, secular and liberal force for the nation. As a result, supporting the perpetuation of Amazigh linguistic identity also became synonymous to making a secular statement as a Muslim. It has led to the telling of Amazigh identity at state museums as one representing the indigenous, pure, diverse, culturally-rich and united Morocco. Reform efforts have also prioritized an amiable look towards the economic and familial links of Moroccan Jews with the few thousand families still left in the country and a showcasing through museums and cultural centers of the Jewish identity as Moroccan first. In that endeavor, it is interesting to note the coverage of Jews as the indigenous of Morocco through the embracing of their “folk” cultural and religious practices, those that are not continued outside Morocco. In this epistemology, the concept of the Moroccan Jew becomes similar to the indigenous Amazigh, both cherished as the oldest peoples of Morocco and symbols of its unity and resilience. In the urban discourse, Amazigh identity is a concept that continues to be part of the deliberations of elites and scholars graduating from French schools on the incorporation of rural and illiterate Morocco in economic and educational advancement. Yet, with the constant influx of migrants from Western Sahara into cities like Fez and Marrakesh, Amazigh has often been described as the umbrella term of those of “mixed” ethnic ancestry who constitute the country’s free population. In sum, Amazigh identity highlights the changing discourse on marginalized communities, human rights, representation, Moroccan nationhood, and regional and transnational politics. The aim of this paper is to analyze perceptions of Amazigh identity in Morocco post-2021 ousting of the Islamist party using data from state-sponsored museum displays and cultural centers collected in Summer 2022 and scholarly analyses of Amazigh identity, representation and rights in Morocco.

Keywords: Amazigh identity, Morocco, representation, state politics

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Authors: A. Knezović

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21st century has transformed the labor market landscape in a way of posing new and different demands on university graduates as well as university lecturers, which means that the knowledge and academic skills students acquire in the course of their studies should be applicable and transferable from the higher education context to their future professional careers. Given the context of the Languages for Specific Purposes (LSP) classroom, the teachers’ objective is not only to teach the language itself, but also to prepare students to use that language as a medium to develop generic skills and competences. These include media and information literacy, critical and creative thinking, problem-solving and analytical skills, effective written and oral communication, as well as collaborative work and social skills, all of which are necessary to make university graduates more competitive in everyday professional environments. On the other hand, due to limitations of time and large numbers of students in classes, the frequently topic-centered syllabus of LSP courses places considerable focus on acquiring the subject matter and specialist vocabulary instead of sufficient development of skills and competences required by students’ prospective employers. This paper intends to explore some of those issues as viewed both by LSP lecturers and by business professionals in their respective surveys. The surveys were conducted among more than 50 LSP lecturers at higher education institutions in Croatia, more than 40 HR professionals and more than 60 university graduates with degrees in economics and/or business working in management positions in mainly large and medium-sized companies in Croatia. Various elements of LSP course content have been taken into consideration in this research, including reading and listening comprehension of specialist texts, acquisition of specialist vocabulary and grammatical structures, as well as presentation and negotiation skills. The ability to hold meetings, conduct business correspondence, write reports, academic texts, case studies and take part in debates were also taken into consideration, as well as informal business communication, business etiquette and core courses delivered in a foreign language. The results of the surveys conducted among LSP lecturers will be analyzed with reference to what extent those elements are included in their courses and how consistently and thoroughly they are evaluated according to their course requirements. Their opinions will be compared to the results of the surveys conducted among professionals from a range of industries in Croatia so as to examine how useful and important they perceive the same elements of the LSP course content in their working environments. Such comparative analysis will thus show to what extent the syllabi of LSP courses meet the demands of the employment market when it comes to the students’ language skills and competences, as well as transferable skills. Finally, the findings will also be compared to the observations based on practical teaching experience and the relevant sources that have been used in this research. In conclusion, the ideas and observations in this paper are merely open-ended questions that do not have conclusive answers, but might prompt LSP lecturers to re-evaluate the content and objectives of their course syllabi.

Keywords: languages for specific purposes (LSP), language skills, topic-centred syllabus, transferable skills

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

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

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

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Authors: Sharma Aseem, Dhurat Rachita, Pawar Varsha, Khalse Manisha

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Introduction: Androgenetic alopecia (AGA) is a prevalent condition characterized by progressive hair thinning driven by genetic and androgen-related factors. The current FDA-approved treatments include oral finasteride and topical minoxidil, though many patients seek combination therapies to enhance results. This study aims to evaluate the effectiveness of a combination therapy involving Minoxidil, Finasteride, and Capixyl™ based on feedback from dermatologists. Methodology: A survey, validated by experts, was distributed to 29 leading dermatologists across India (in Tier 1 and 2 cities). The survey examined real-world clinical experiences, focusing on patient outcomes and the overall effectiveness of the mentioned formulation. Results: Among the surveyed dermatologists, 41.4% identified women aged 35-40 as the most frequently diagnosed with female pattern hair loss. The combination therapy with Minoxidil, Finasteride, and Capixyl™ was utilized by 34.5% of dermatologists for over 60 patients per month. The majority highlighted the benefits of this combination therapy, which acts via multiple mechanisms, such as vasodilation and dihydrotestosterone (DHT) receptor blockade, resulting in improved hair regrowth. Additionally, patients demonstrated better clinical outcomes, enhanced compliance, and fewer side effects. Demographically, younger patients, particularly those with AGA for less than 10 years, responded more positively to the treatment. Early intervention led to quicker and more significant results. Overall satisfaction among dermatologists was high, with 86.2% expressing positive feedback on the therapy. In terms of treatment outcomes, 51.7% of dermatologists observed visible results within 4-6 months, while 34.5% noticed a significant reduction in hair fall within 8-12 weeks. Improvements in scalp health were reported by 48.3%, and 51.7% saw an increased hair density within 3-4 months. Despite mild side effects such as scalp irritation, dryness, flaking, and occasional issues like folliculitis, headaches, itching, and redness, patient satisfaction remained high. Dermatologists reported that 93.1% of patients experienced faster and better hair regrowth with Capixyl™ compared to Minoxidil alone. Suggestions for improving the formulation included incorporating peptides like Saw Palmetto and enhancing product packaging to better meet patient needs. Discussion: The combination of Minoxidil, Finasteride, and Capixyl™ yielded positive clinical outcomes, especially in improving hair density, scalp health, and overall patient satisfaction. Dermatologists found that Capixyl™ peptides enhanced the therapeutic effect, promoting hair regrowth and improving compliance. While side effects were generally mild, there were suggestions to further improve the formulation by adding additional peptides like Saw Palmetto. Conclusion: The combination of Minoxidil and Finasteride fortified with Capixyl™ presents a promising therapeutic option for managing AGA. Dermatologists reported significant improvements in hair density, scalp health, and patient satisfaction. With its favorable efficacy and manageable side effects, this formulation proves to be a valuable addition to the treatment landscape for AGA.

Keywords: androgenetic alopecia, combination therapy, minoxidil, finasteride, capixyl

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

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

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

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Authors: K. A.Veselova, N. V.Gromova, I. N.Antonova, I. N. Kalakutskii

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There are many diseases and incidents that may result facial defects and deformities: cancer, trauma, burns, congenital anomalies, and autoimmune diseases. In some cases, patient may acquire atypically extensive facial defect, including more than one anatomical region or, by contrast, atypically small defect (e.g. partial auricular defect). The anaplastology gives us opportunity to help patient with facial disfigurement in cases when plastic surgery is contraindicated. Using of implant retention for facial prosthesis is strongly recommended because improves both aesthetic and functional results and makes using of the prosthesis more comfortable. Prostheticly oriented fixture position is extremely important for aesthetic and functional long-term result; however, the optimal site for fixture placement is not clear in cases with atypical configuration of facial defect. The objective of this report is to demonstrate challenges in fixture position determination we have faced with and offer the solution. In this report, four cases of implant-supported facial prosthesis are described. Extra-oral implants with four millimeter length were used in all cases. The decision regarding the quantity of surgical stages was based on anamnesis of disease. Facial prostheses were manufactured according to conventional technique. Clinical and technological difficulties and mistakes are described, and prostheticly oriented approach for determination of fixture position is demonstrated. The case with atypically large combined orbital and nasal defect resulting after arteriovenous malformation is described: the correct positioning of artificial eye was impossible due to wrong position of the fixture (with suprastructure) located in medial aspect of supraorbital rim. The suprastructure was unfixed and this fixture wasn`t used for retention in order to achieve appropriate artificial eye placement and better aesthetic result. In other case with small partial auricular defect (only helix and antihelix were absent) caused by squamoized cell carcinoma T1N0M0 surgical template was used to avoid the difficulties. To achieve the prostheticly oriented fixture position in case of extremely small defect the template was made on preliminary cast using vacuum thermoforming method. Two radiopaque markers were incorporated into template in preferable for fixture placement positions taking into account future prosthesis configuration. The template was put on remaining ear and cone-beam CT was performed to insure, that the amount of bone is enough for implant insertion in preferable position. Before the surgery radiopaque markers were extracted and template was holed for guide drill. Fabrication of implant-retained facial prostheses gives us opportunity to improve aesthetics, retention and patients’ quality of life. But every inaccuracy in planning leads to challenges on surgery and prosthetic stages. Moreover, in cases with atypically small or extended facial defects prostheticly oriented approach for determination of fixture position is strongly required. The approach including surgical template fabrication is effective, easy and cheap way to avoid mistakes and unpredictable result.

Keywords: anaplastology, facial prosthesis, implant-retained facial prosthesis., maxillofacil prosthese

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Authors: Mirain Rhys, Kevin Smith

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In 2017, the Welsh Government introduced an ambitious, new strategy to increase the number of Welsh speakers in Wales to 1 million by 2050. The Welsh education system is a vitally important feature of this strategy. All children attending state schools in Wales learn Welsh as a second language until the age of 16 and are assessed at General Certificate of Secondary Education (GCSE) level. In 2013, a review of Welsh second language instruction in Key Stages 3 and 4 was completed. The report identified considerable gaps in teachers’ preparation and training for teaching Welsh; poor Welsh language ethos at many schools; and a general lack of resources to support the instruction of Welsh. Recommendations were made across a number of dimensions including curriculum content, pedagogical practice, and teacher assessment, training, and resources. With a new national curriculum currently in development, this study builds on this review and provides unprecedented detail into pupils’ and teachers’ perceptions of Welsh language instruction. The current research built on data taken from an existing capacity building research project on Welsh education, the Wales multi-cohort study (WMS). Quantitative data taken from WMS surveys with over 1200 pupils in schools in Wales indicated that Welsh language lessons were the least enjoyable subject among pupils. The current research aimed to unpick pupil experiences in order to add to the policy development context. To achieve this, forty-four pupils and four teachers in three schools from the larger WMS sample participated in focus groups. Participants from years 9, 11 and 13 who had indicated positive, negative and neutral attitudes towards the Welsh language in a previous WMS survey were selected. Questions were based on previous research exploring issues including, but not limited to pedagogy, policy, assessment, engagement and (teacher) training. A thematic analysis of the focus group recordings revealed that the majority of participants held positive views around keeping the language alive but did not want to take on responsibility for its maintenance. These views were almost entirely based on their experiences of learning Welsh at school, especially in relation to their perceived lack of choice and opinions around particular lesson strategies and assessment. Analysis of teacher interviews highlighted a distinct lack of resources (materials and staff alike) compared to modern foreign languages, which had a negative impact on student motivation and attitudes. Both staff and students indicated a need for more practical, oral language instruction which could lead to Welsh being used outside the classroom. The data corroborate many of the review’s previous findings, but what makes this research distinctive is the way in which pupils poignantly address generally misguided aims for Welsh language instruction, poor pedagogical practice and a general disconnect between Welsh instruction and its daily use in their lives. These findings emphasize the complexity of incorporating the educational sector in strategies for Welsh language maintenance and the complications arising from pedagogical training, support, and resources, as well as teacher and pupil perceptions of, and attitudes towards, teaching and learning Welsh.

Keywords: bilingual education, language maintenance, language revitalisation, minority languages, Wales

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Authors: Charlotte Jeavons, Charitini Stavropoulous, Nicolas Drey

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Background: Over one-third of five-year-olds and almost half of all eight-year-olds in the UK have obvious caries experience that can be detected by visual screening techniques. School-based caries preventions programs to apply fluoride varnish to young children’s teeth operate in many areas in the UK. Their aim is to reduce dental caries in children. The Department of Health guidance (2009) on consent states information must be provided to parents to enable informed autonomous decision-making prior to any treatment involving their young children. Fluoride varnish schemes delivered in primary schools use letters for this purpose. Parents are expected to return these indicating their consent or refusal. A large proportion of parents do not respond. In the absence of positive consent, these children are excluded from the program. Non-response is more common in deprived areas creating inequality. The reason for this is unknown. The consent process used is underpinned by the ethical theory of deontology that is prevalent in clinical dentistry and widely accepted in bio-ethics. Objective: To investigate parents’ views, understanding and experience of the fluoride varnish program taking place in their child’s school, including their views about the practical consent arrangements. Method: Schools participating in the fluoride varnish scheme operating in Enfield, North London, were asked to take part. Parents with children in nursery, reception, or year one were invited to participate via semi-structured interviews and focus groups. Thematic analysis was conducted. Findings: 40 parents were recruited from eight schools. The global theme of ‘trust’ was identified as the strongest influence on parental responses. Six themes were identified; protecting children from harm is viewed by parents as their role, parents have the capability to decide but lack confidence, sharing responsibility for their child’s oral health with the State is welcomed by a parent, existing relationships within parents’ social networks strongly influences consent decisions, official dental information is not communicated effectively, sending a letter to parents’ and excluding them from meeting dental practitioners is ineffective. The information delivered via a letter was not strongly identified by parents as influencing their response. Conclusions: Personal contact with the person(s) providing information and requesting consent has a greater impact on parental consent responses than written information provided alone. This demonstrates that traditional bio-ethical ideas about rational decision-making where emotions are transcended and interference is not justified unless preventing harm to an unaware person are outdated. Parental decision-making is relational and the consent process should be adapted to reflect this. The current system that has a deontology view of decision making at its core impoverishes parental autonomy and may, ultimately, increase dental inequalities as a result.

Keywords: consent, decision, ethics, fluoride, parents

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Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

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Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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Authors: Emily Moore, Andrew Gaukroger, Matthew Solan, Lucy Bailey, Alexandra Boxall, Andrew Carne, Chintu Gadamsetty, Charlotte Morley, Katy Western, Iwona Kolodziejczyk

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Introduction: Rupture of the Achilles tendon is common and has a long recovery period. Most cases are managed non-operatively. Foot and Ankle Surgeons advise an ultrasound scan to check the gap between the torn ends. A large gap (with the ankle in equinus) is a relative indication for surgery. The definitive decision regarding surgical versus non-operative management can only be made once an ultrasound scan is undertaken and the patient is subsequently reviewed by a Foot and Ankle surgeon. To get to this point, the patient journey involves several hospital departments. In nearby trusts, patients reattend for a scan and go to the plaster room both before and after the ultrasound for removal and re-application of the cast. At a third visit to the hospital, the surgeon and patient discuss options for definitive treatment. It may take 2-3 weeks from the initial Emergency Department visit before the final treatment decision is made. This “wasted time” is ultimately added to the recovery period for the patient. In this hospital, Achilles rupture patients are seen in a weekly multidisciplinary OneStop Heel Pain clinic. This pathway was already efficient but subject to occasional frustrating delays if a key staff member was absent. A new pathway was introduced with the goal to reduce delays to a definitive treatment plan. Method: A retrospective series of Achilles tendon ruptures managed according to the 2019 protocol was identified. Time taken from the Emergency Department to have both an ultrasound scan and specialist Foot and Ankle surgical review were calculated. 30 consecutive patients were treated with our new pathway and prospectively followed. The time taken for a scan and for specialist review were compared to the 30 consecutive cases from the 2019 (pre-COVID) cohort. The new pathway includes 1. A new contoured splint applied to the front of the injured limb held with a bandage. This can be removed and replaced (unlike a plaster cast) in the ultrasound department, removing the need for plaster room visits. 2. Urgent triage to a Foot and Ankle specialist. 3. Ultrasound scan for assessment of rupture gap and deep vein thrombosis check. 4. Early decision regarding surgery. Transfer to weight bearing in a prosthetic boot in equinuswithout waiting for the once-a-week clinic. 5. Extended oral VTE prophylaxis. Results: The time taken for a patient to have both an ultrasound scan and specialist review fell > 50%. All patients in the new pathway reached a definitive treatment decision within one week. There were no significant differences in patient demographics or rates of surgical vs non-operative treatment. The mean time from Emergency Department visit to specialist review and ultrasound scan fell from 8.7 days (old protocol) to 2.9 days (new pathway). The maximum time for this fell from 23 days (old protocol) to 6 days (new pathway). Conclusion: Teamwork and innovation have improved the experience for patients with an Achilles tendon rupture. The new pathway brings many advantages - reduced time in the Emergency Department, fewer hospital visits, less time using crutches and reduced overall recovery time.

Keywords: orthopaedics, achilles rupture, ultrasound, innovation

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Abiodun Amusan, Olugbenga Akinola, Kazeem Akano, María Hernández-Castañeda, Jenna Dick, Akintunde Sowunmi, Geoffrey Hart, Grace Gbotosho

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Introduction: Artemisinin-based Combination Therapy (ACTs) is the cornerstone malaria treatment option in most malaria-endemic countries. Unfortunately, the malaria control effort is constantly being threatened by resistance of Plasmodium falciparum to ACTs. The recent evidence of artemisinin resistance in East Africa and its possibility of spreading to other African regions portends an imminent health catastrophe. This study aimed at evaluating the occurrence, prevalence, and influence of artemisinin-resistance markers on treatment outcomes in Ibadan before and after post-adoption of artemisinin combination therapy (ACTs) in Nigeria in 2005. Method: The study involved day zero dry blood spot (DBS) obtained from malaria patients during retrospective (2000-2005) and prospective (2021) studies. A cohort in the prospective study received oral dihydroartemisinin-piperaquine and underwent a 42-day follow-up to observe treatment outcomes. Genomic DNA was extracted from the DBS samples using a QIAamp blood extraction kit. Fragments of P. falciparum kelch13 (Pfkelch13), P. falciparum coronin (Pfcoronin), P. falciparum multidrug resistance 2 (PfMDR2), and P. falciparum chloroquine resistance transporter (PfCRT) genes were amplified and sequenced on a sanger sequencing platform to identify artemisinin resistance-associated mutations. Mutations were identified by aligning sequenced data with reference sequences obtained from the National Center for Biotechnology Information. Data were analyzed using descriptive statistics and student t-tests. Results: Mean parasite clearance time (PCT) and fever clearance time (FCT) were 2.1 ± 0.6 days (95% CI: 1.97-2.24) and 1.3 ± 0.7 days (95% CI: 1.1-1.6) respectively. Four mutations, K189T [34/53(64.2%)], R255K [2/53(3.8%)], K189N [1/53(1.9%)] and N217H [1/53(1.9%)] were identified within the N-terminal (Coiled-coil containing) domain of Pfkelch13. No artemisinin resistance-associated mutation usually found within the β-propeller domain of the Pfkelch13 gene was found in these analyzed samples. However, K189T and R255K mutations showed a significant correlation with longer parasite clearance time in the patients (P<0.002). The observed Pfkelch13 gene changes did not influence the baseline mean parasitemia (P = 0.44). P76S [17/100 (17%)] and V62M [1/100 (1%)] changes were identified in the Pfcoronin gene fragment without any influence on the parasitological parameters. No change was observed in the PfMDR2 gene, while no artemisinin resistance-associated mutation was found in the PfCRT gene. Furthermore, a sample each in the retrospective study contained the Pfkelch13 K189T and Pfcoronin P76S mutations. Conclusion: The study revealed absence of genetic-based evidence of artemisinin resistance in the study population at the time of study. The high frequency of K189T Pfkelch13 mutation and its correlation with increased parasite clearance time in this study may depict geographical variation of resistance mediators and imminent artemisinin resistance, respectively. The study also revealed an inherent potential of parasites to harbour drug-resistant genotypes before the introduction of ACTs in Nigeria.

Keywords: artemisinin resistance, plasmodium falciparum, Pfkelch13 mutations, Pfcoronin

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Authors: Ibrahim Abdulla Labib, Medhat Mohamed Morsy, Gamal Hosny, Hanan Dawood Yassa, Gaber Hassan

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Amiodarone is a very effective drug, widely used for arrhythmia. Unfortunately it has many side effects involving many organs especially thyroid gland. The current work was conducted to elucidate the effect of amiodarone on the thyroid gland and the possible protective role of vitamin E. Fifty adult male albino rats weighed 200 – 250 grams were divided into five groups; ten rats each. Group I (Control): Five rats were sacrificed after three weeks and five rats were sacrificed after six weeks. Group II (Sham control): Each rat received sunflower oil orally; the solvent of vitamin E for three weeks. Group III (Amiodarone-treated): each rat received an oral dose of amiodarone; 150 mg/kg/day for three weeks. Group IV (Recovery): Each rat received amiodarone as group III then the drug was stopped for three weeks to evaluate recovery. Group V (Amiodarone + Vitamin E-treated): Each rat received amiodarone as group III followed by 100 mg/kg/day vitamin E orally for three weeks. Thyroid gland of the sacrificed animals were dissected out and prepared for light and electron microscopic studies. Amiodarone administration resulted in loss of normal follicular architecture as many follicles appeared either shrunken, empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells while others showed interruption of their membrane. Masson's Trichrome stained sections showed increased collagen fibers in between the thyroid follicles. Ultrastructurally, the apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular with chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum with numerous lysosomes. After three weeks of stopping amiodarone, the follicles were nearly regular in outline. Some follicles were filled with homogenous eosinophilic colloid and others had shrunken pale colloid or were empty. Some few follicles showed exfoliated cells in their lumina and others were still lined by more than one layer of follicular cells. Moderate amounts of collagen fibers were observed in-between thyroid follicles. Ultrastructurally, many follicular cells had rounded euchromatic nucleui, moderate number of lysosomes and moderately dilated rough endoplasmic reticulum. However, few follicular cells still showing irregular nucleui, dilated rough endoplasmic reticulum and many cytoplasmic vacuoles. Administration of vitamin E with amiodarone for three weeks resulted in obvious structural improvement. Most of the follicles were lined by a single layer of cuboidal cells and the lumina were filled with homogenous eosinophilic colloid with very few vacuolations. The majority of follicular cells had rounded nuclei with occasional detection of ballooned cells and dark nuclei. Scanty collagen fibers were detected among thyroid follicles. Ultrastructurally, most follicular cells exhibited rounded euchromatic nuclei with few short microvilli were projecting into the colloid. Few lysosomes were also noticed. It was concluded that amiodarone administration leads to many adverse histological changes in the thyroid gland. Some of these changes are reversible during the recovery period however concomitant vitamin E administration with amiodarone has a major protective role in preventing many of these changes.

Keywords: amiodarone, recovery, ultrastructure, vitamin E.

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Authors: Panagiota Katsikouli, William Hamilton Byrne, Thomas Gammeltoft-Hansen, Tijs Slaats

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An individual who demonstrates a well-founded fear of persecution or faces real risk of being subjected to torture is eligible for asylum. In Danish law, the exact legal thresholds reflect those established by international conventions, notably the 1951 Refugee Convention and the 1950 European Convention for Human Rights. These international treaties, however, remain largely silent when it comes to how states should assess asylum claims. As a result, national authorities are typically left to determine an individual’s legal eligibility on a narrow basis consisting of an oral testimony, which may itself be hampered by several factors, including imprecise language interpretation, insecurity or lacking trust towards the authorities among applicants. The leaky ground, on which authorities must assess their subjective perceptions of asylum applicants' credibility, questions whether, in all cases, adjudicators make the correct decision. Moreover, the subjective element in these assessments raises questions on whether individual asylum cases could be afflicted by implicit biases or stereotyping amongst adjudicators. In fact, recent studies have uncovered significant correlations between decision outcomes and the experience and gender of the assigned judge, as well as correlations between asylum outcomes and entirely external events such as weather and political elections. In this study, we analyze a publicly available dataset containing approximately 8,000 summaries of asylum cases, initially rejected, and re-tried by the Refugee Appeals Board (RAB) in Denmark. First, we look for variations in the recognition rates, with regards to a number of applicants’ features: their country of origin/nationality, their identified gender, their identified religion, their ethnicity, whether torture was mentioned in their case and if so, whether it was supported or not, and the year the applicant entered Denmark. In order to extract those features from the text summaries, as well as the final decision of the RAB, we applied natural language processing and regular expressions, adjusting for the Danish language. We observed interesting variations in recognition rates related to the applicants’ country of origin, ethnicity, year of entry and the support or not of torture claims, whenever those were made in the case. The appearance (or not) of significant variations in the recognition rates, does not necessarily imply (or not) bias in the decision-making progress. None of the considered features, with the exception maybe of the torture claims, should be decisive factors for an asylum seeker’s fate. We therefore investigate whether the decision can be predicted on the basis of these features, and consequently, whether biases are likely to exist in the decisionmaking progress. We employed a number of machine learning classifiers, and found that when using the applicant’s country of origin, religion, ethnicity and year of entry with a random forest classifier, or a decision tree, the prediction accuracy is as high as 82% and 85% respectively. tentially predictive properties with regards to the outcome of an asylum case. Our analysis and findings call for further investigation on the predictability of the outcome, on a larger dataset of 17,000 cases, which is undergoing.

Keywords: asylum adjudications, automated decision-making, machine learning, text mining

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Authors: B. R. Campomanes-Alvarez, P. Quiros, B. Fernandez

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Automatic Speech Recognition (ASR) is a machine-based process of decoding and transcribing oral speech. A typical ASR system receives acoustic input from a speaker or an audio file, analyzes it using algorithms, and produces an output in the form of a text. Some speech recognition systems use Hidden Markov Models (HMMs) to deal with the temporal variability of speech and Gaussian Mixture Models (GMMs) to determine how well each state of each HMM fits a short window of frames of coefficients that represents the acoustic input. Another way to evaluate the fit is to use a feed-forward neural network that takes several frames of coefficients as input and produces posterior probabilities over HMM states as output. Deep neural networks (DNNs) that have many hidden layers and are trained using new methods have been shown to outperform GMMs on a variety of speech recognition systems. Acoustic models for state-of-the-art ASR systems are usually training on massive amounts of data. However, audio files with their corresponding transcriptions can be difficult to obtain, especially in the Spanish language. Hence, in the case of these low-resource scenarios, building an ASR model is considered as a complex task due to the lack of labeled data, resulting in an under-trained system. Semi-supervised learning approaches arise as necessary tasks given the high cost of transcribing audio data. The main goal of this proposal is to develop a procedure based on acoustic semi-supervised learning for Spanish ASR systems by using DNNs. This semi-supervised learning approach consists of: (a) Training a seed ASR model with a DNN using a set of audios and their respective transcriptions. A DNN with a one-hidden-layer network was initialized; increasing the number of hidden layers in training, to a five. A refinement, which consisted of the weight matrix plus bias term and a Stochastic Gradient Descent (SGD) training were also performed. The objective function was the cross-entropy criterion. (b) Decoding/testing a set of unlabeled data with the obtained seed model. (c) Selecting a suitable subset of the validated data to retrain the seed model, thereby improving its performance on the target test set. To choose the most precise transcriptions, three confidence scores or metrics, regarding the lattice concept (based on the graph cost, the acoustic cost and a combination of both), was performed as selection technique. The performance of the ASR system will be calculated by means of the Word Error Rate (WER). The test dataset was renewed in order to extract the new transcriptions added to the training dataset. Some experiments were carried out in order to select the best ASR results. A comparison between a GMM-based model without retraining and the DNN proposed system was also made under the same conditions. Results showed that the semi-supervised ASR-model based on DNNs outperformed the GMM-model, in terms of WER, in all tested cases. The best result obtained an improvement of 6% relative WER. Hence, these promising results suggest that the proposed technique could be suitable for building ASR models in low-resource environments.

Keywords: automatic speech recognition, deep neural networks, machine learning, semi-supervised learning

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Authors: Atin Adhikari, Sushma Kurella, Pratik Banerjee, Nabanita Mukherjee, Yamini M. Chandana Gollapudi, Bushra Shah

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Different sharp instruments, drilling machines, and high speed rotary instruments are routinely used in dental clinics during dental cleaning. Therefore, these cleaning procedures release a lot of oral microorganisms including bacteria in clinic air and may cause significant occupational bioaerosol exposure risks for dentists, dental hygienists, patients, and dental clinic employees. Two major goals of this study were to quantify volumetric airborne concentrations of bacteria and to assess overall microbial activity in this type of occupational environment. The study was conducted in several dental clinics of southern Georgia and 15 dental cleaning procedures were targeted for sampling of airborne bacteria and testing of overall microbial activity in settled dusts over clinic floors. For air sampling, a Biostage viable cascade impactor was utilized, which comprises an inlet cone, precision-drilled 400-hole impactor stage, and a base that holds an agar plate (Tryptic soy agar). A high-flow Quick-Take-30 pump connected to this impactor pulls microorganisms in air at 28.3 L/min flow rate through the holes (jets) where they are collected on the agar surface for approx. five minutes. After sampling, agar plates containing the samples were placed in an ice chest with blue ice and plates were incubated at 30±2°C for 24 to 72 h. Colonies were counted and converted to airborne concentrations (CFU/m3) followed by positive hole corrections. Most abundant bacterial colonies (selected by visual screening) were identified by PCR amplicon sequencing of 16S rRNA genes. For understanding overall microbial activity in clinic floors and estimating a general cleanliness of the clinic surfaces during or after dental cleaning procedures, ATP levels were determined in swabbed dust samples collected from 10 cm2 floor surfaces. Concentration of ATP may indicate both the cell viability and the metabolic status of settled microorganisms in this situation. An ATP measuring kit was used, which utilized standard luciferin-luciferase fluorescence reaction and a luminometer, which quantified ATP levels as relative light units (RLU). Three air and dust samples were collected during each cleaning procedure (at the beginning, during cleaning, and immediately after the procedure was completed (n = 45). Concentrations at the beginning, during, and after dental cleaning procedures were 671±525, 917±1203, and 899±823 CFU/m3, respectively for airborne bacteria and 91±101, 243±129, and 139±77 RLU/sample, respectively for ATP levels. The concentrations of bacteria were significantly higher than typical indoor residential environments. Although an increasing trend for airborne bacteria was observed during cleaning, the data collected at three different time points were not significantly different (ANOVA: p = 0.38) probably due to high standard deviations of data. The ATP levels, however, demonstrated a significant difference (ANOVA: p <0.05) in this scenario indicating significant change in microbial activity on floor surfaces during dental cleaning. The most common bacterial genera identified were: Neisseria sp., Streptococcus sp., Chryseobacterium sp., Paenisporosarcina sp., and Vibrio sp. in terms of frequencies of occurrences, respectively. The study concluded that bacterial exposure in dental clinics could be a notable occupational biohazard, and appropriate respiratory protections for the employees are urgently needed.

Keywords: bioaerosols, hospital hygiene, indoor air quality, occupational biohazards

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Authors: Jacqueline Eleonora Ek, Michael Spiteri, Chris Giordimaina, Pierre Agius

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Background: Malta is known for being a key player as a frontline country with regard to irregular immigration from Africa to Europe. Every year the island experiences an influx of migrants as boat movement across the Mediterranean continues to be a humanitarian challenge. Irregular immigration and applying for asylum is both a lengthy and mentally demanding process. Those doing so are often faced with multiple challenges, which can adversely affect their mental health. Between January and August 2020, Malta disembarked 2 162 people rescued at sea, 463 of them between July & August. Given the small size of the Maltese islands, this regulation places a disproportionately large burden on the country, creating a backlog in the processing of asylum applications resulting in increased time periods of detention. These delays reverberate throughout multiple management pathways resulting in prolonged periods of detention and challenging access to health services. Objectives: To better understand the spatial dimensions of this humanitarian crisis, this study aims to assess disparities in the acute medical management of migrants presenting to the emergency department (ED) with acute mental health presentations as compared to that of local and non-local residents. Method: In this retrospective study, 17795 consecutive ED attendances were reviewed to look for acute mental health presentations. These were further evaluated to assess discrepancies in transportation routes to hospital, nature of presenting complaint, effects of language barriers, use of CT brain, treatment given at ED, availability of psychiatric reviews, and final admission/discharge plans. Results: Of the ED attendances, 92.3% were local residents, and 7.7% were non-locals. Of the non-locals, 13.8% were migrants, and 86.2% were other-non-locals. Acute mental health presentations were seen in 1% of local residents; this increased to 20.6% in migrants. 56.4% of migrants attended with deliberate self-harm; this was lower in local residents, 28.9%. Contrastingly, in local residents, the most common presenting complaint was suicidal thought/ low mood 37.3%, the incidence was similar in migrants at 33.3%. The main differences included 12.8% of migrants presenting with refused oral intake while only 0.6% of local residents presented with the same complaints. 7.7% of migrants presented with a reduced level of consciousness, no local residents presented with this same issue. Physicians documented a language barrier in 74.4% of migrants. 25.6% were noted to be completely uncommunicative. Further investigations included the use of a CT scan in 12% of local residents and in 35.9% of migrants. The most common treatment administered to migrants was supportive fluids 15.4%, the most common in local residents was benzodiazepines 15.1%. Voluntary psychiatric admissions were seen in 33.3% of migrants and 24.7% of locals. Involuntary admissions were seen in 23% of migrants and 13.3% of locals. Conclusion: Results showed multiple disparities in health management. A meeting was held between entities responsible for migrant health in Malta, including the emergency department, primary health care, migrant detention services, and Malta Red Cross. Currently, national quality-improvement initiatives are underway to form new pathways to improve patient-centered care. These include an interpreter unit, centralized handover sheets, and a dedicated migrant health service.

Keywords: emergency department, communication, health, migration

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Authors: Dina Farran, Mark Ashworth, Fiona Gaughran

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Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of stroke, contributing to heart failure and death. In this project, we aim to improve patient safety by screening for stroke risk among people with AF and co-morbid mental illness. To do so, we started by conducting a systematic review and meta-analysis on prevalence, management, and outcomes of AF in people with Serious Mental Illness (SMI) versus the general population. We then evaluated oral anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI in King’s College Hospital. We also evaluated the association between mental illness severity and OAC prescription in eligible patients in South London and Maudsley (SLaM) NHS Foundation Trust. Next, we implemented an electronic clinical decision support system (eCDSS) consisting of a visual prompt on patient electronic Personal Health Records to screen for AF-related stroke risk in three Mental Health of Older Adults wards at SLaM. Finally, we assessed the feasibility and acceptability of the eCDSS by qualitatively investigating clinicians’ perspectives of the potential usefulness of the eCDSS (pre-intervention) and their experiences and their views regarding its impact on clinicians and patients (post-intervention). The systematic review showed that people with SMI had low reported rates of AF. AF patients with SMI were less likely to receive OAC than the general population. When receiving warfarin, people with SMI, particularly bipolar disorder, experienced poor anticoagulation control compared to the general population. Meta-analysis showed that SMI was not significantly associated with an increased risk of stroke or major bleeding when adjusting for underlying risk factors. The main findings of the first observational study were that among AF patients having a high stroke risk, those with co-morbid SMI were less likely than non-SMI to be prescribed any OAC, particularly warfarin. After 2019, there was no significant difference between the two groups. In the second observational study, patients with AF and co-morbid SMI were less likely to be prescribed any OAC compared to those with dementia, substance use disorders, or common mental disorders, adjusting for age, sex, stroke, and bleeding risk scores. Among AF patients with co-morbid SMI, warfarin was less likely to be prescribed to those having alcohol or substance dependency, serious self-injury, hallucinations or delusions, and activities of daily living impairment. In the intervention, clinicians were asked to confirm the presence of AF, clinically assess stroke and bleeding risks, record risk scores in clinical notes, and refer patients at high risk of stroke to OAC clinics. Clinicians reported many potential benefits for the eCDSS, including improving clinical effectiveness, better identification of patients at risk, safer and more comprehensive care, consistency in decision making and saving time. Identified potential risks included rigidity in decision-making, overreliance, reduced critical thinking, false positive recommendations, annoyance, and increased workload. This study presents a unique opportunity to quantify AF patients with mental illness who are at high risk of severe outcomes using electronic health records. This has the potential to improve health outcomes and, therefore patients' quality of life.

Keywords: atrial fibrillation, stroke, mental health conditions, electronic clinical decision support systems

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Authors: A. Bhatt, C. Bassi, H. Farragher, J. Musk

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Background: All medicines placed on the EU market are legally required to be accompanied by labeling and package leaflet, which provide comprehensive information, enabling its safe and appropriate use. Mock-ups with results of assessments using a target patient group must be submitted for a marketing authorisation application. Consumers need confidence in non-prescription, OTC medicines in order to manage their minor ailments and umbrella brands assist purchasing decisions by assisting easy identification within a particular therapeutic area. A number of regulatory agencies have risk management tools and guidelines to assist in developing umbrella brands for OTC medicines, however assessment and decision making is subjective and inconsistent. This study presents an evaluation in the UK following the US FDA warning concerning methaemoglobinaemia following 21 reported cases (11 children under 2 years) caused by OTC oral analgesics containing benzocaine. METHODS: A standard face to face, 25 structured task based user interview testing methodology using a standard questionnaire and rating scale in consumers aged 15-91 years, was conducted independently between June and October 2015 in their homes. Whether individuals could discriminate between the labelling, safety information and warnings on cartons and PILs between 3 different OTC medicines packs with the same umbrella name was evaluated. Each pack was presented with differing information hierarchy using, different coloured cartons, containing the 3 different active ingredients, benzocaine (oromucosal spray) and two lozenges containing 2, 4, dichlorobenzyl alcohol, amylmetacresol and hexylresorcinol respectively (for the symptomatic relief of sore throat pain). The test was designed to determine whether warnings on the carton and leaflet were prominent, accessible to alert users that one product contained benzocaine, risk of methaemoglobinaemia, and refer to the leaflet for the signs of the condition and what to do should this occur. Results: Two consumers did not locate the warnings on the side of the pack, eventually found them on the back and two suggestions to further improve accessibility of the methaemoglobinaemia warning. Using a gold pack design for the oromucosal spray, all consumers could differentiate between the 3 drugs, minimum age particulars, pharmaceutical form and the risk factor methaemoglobinaemia. The warnings for benzocaine were deemed to be clear or very clear; appearance of the 3 packs were either very well differentiated or quite well differentiated. The PIL test passed on all criteria. All consumers could use the product correctly, identify risk factors ensuring the critical information necessary for the safe use was legible and easily accessible so that confusion and errors were minimised. Conclusion: Patients with known methaemoglobinaemia are likely to be vigilant in checking for benzocaine containing products, despite similar umbrella brand names across a range of active ingredients. Despite these findings, the package design and spray format were not deemed to be sufficient to mitigate potential safety risks associated with differences in target populations and contraindications when submitted to the Regulatory Agency. Although risk management tools are increasingly being used by agencies to assist in providing objective assurance of package safety, further transparency, reduction in subjectivity and proportionate risk should be demonstrated.

Keywords: labelling, OTC, risk, user testing

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Authors: Pei-Shan Liang

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Objective: This article explores the care experience of a terminal lung cancer patient who developed lower limb paralysis after surgery for aortic dissection. The patient, diagnosed with aortic dissection during chemotherapy for lung cancer, faced post-surgical lower limb paralysis, leading to feelings of helplessness and hopelessness as they approached death with reduced mobility. Methods: The nursing period was from July 19 to July 27, during which the author, alongside the intensive care team and palliative care specialists, conducted a comprehensive assessment through observation, direct care, conversations, physical assessments, and medical record review. Gordon's eleven functional health patterns were used for a holistic evaluation, identifying four nursing health issues: "pain related to terminal lung cancer and invasive procedures," "decreased cardiac tissue perfusion due to hemodynamic instability," "impaired physical mobility related to lower limb paralysis," and "hopelessness due to the unpredictable prognosis of terminal lung cancer." Results: The medical team initially focused on symptom relief, administering Morphine 5mg in 0.9% N/S 50ml IVD q6h for pain management and continuing chemotherapy as prescribed. Open communication was employed to address the patient's physical, psychological, and spiritual concerns. Non-pharmacological interventions, including listening, caring, companionship, opioid medication, and distraction techniques like comfortable positioning and warm foot baths, were used to alleviate pain, reducing the pain score to 3 on the numeric rating scale and easing respiratory discomfort. The palliative care team was also involved, guiding the patient and family through the "Four Paths of Life," helping the patient achieve a good end-of-life experience and the family to experience a peaceful life. This process also served to promote the concept of palliative care, enabling more patients and families to receive high-quality and dignified care. The patient was encouraged to express inner anxiety through drawing or writing, which helped reduce the hopelessness caused by psychological distress and uncertainty about the disease's prognosis, as assessed by the Hospital Anxiety and Depression Scale, reaching a level of mild anxiety but acceptable without affecting sleep. Conclusion: What left a deep impression during the care process was the need for intensive care providers to consider the patient's psychological state, not just their physical condition, when the patient's situation changes. Family support and involvement often provide the greatest solace for the patient, emphasizing the importance of comfort and dignity. This includes oral care to maintain cleanliness and comfort, frequent repositioning to alleviate pressure and discomfort, and timely removal of invasive devices and unnecessary medications to avoid unnecessary suffering. The nursing process should also address the patient's psychological needs, offering comfort and support to ensure that they can face the end of life with peace and dignity.

Keywords: intensive care, lung cancer, aortic dissection, lower limb paralysis

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Authors: N. Reza Pour, S. Chuah, T. Vo

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Background: Vertebral artery dissection (VAD) is a rare complication of pregnancy. It can occur spontaneously or following a traumatic event. The pathogenesis is unclear. Predisposing factors include chronic hypertension, Marfan’s syndrome, fibromuscular dysplasia, vasculitis and cystic medial necrosis. Physiological changes of pregnancy have also been proposed as potential mechanisms of injury to the vessel wall. The clinical presentation varies and it can present as a headache, neck pain, diplopia, transient ischaemic attack, or an ischemic stroke. Isolated cases of VAD in pregnancy and puerperium have been reported in the literature. One case was found to have posterior circulation stroke as a result of bilateral VAD and labour was induced at 37 weeks gestation for preeclampsia. Another patient at 38 weeks with severe neck pain that persisted after induction for elevated blood pressure and arteriography showed right VAD postpartum. A single case of lethal VAD in pregnancy with subsequent massive subarachnoid haemorrhage has been reported which was confirmed by the autopsy. Case Presentation: We report two cases of vertebral artery dissection in pregnancy. The first patient was a 32-year-old primigravida presented at the 38th week of pregnancy with the onset of early labour and blood pressure (BP) of 130/70 on arrival. After 2 hours, the patient developed a severe headache with blurry vision and BP was 238/120. Despite treatment with an intravenous antihypertensive, she had eclamptic fit. Magnesium solfate was started and Emergency Caesarean Section was performed under the general anaesthesia. On the second day after the operation, she developed left-sided neck pain. Magnetic Resonance Imaging (MRI) angiography confirmed a short segment left vertebral artery dissection at the level of C3. The patient was treated with aspirin and remained stable without any neurological deficit. The second patient was a 33-year-old primigavida who was admitted to the hospital at 36 weeks gestation with BP of 155/105, constant headache and visual disturbances. She was medicated with an oral antihypertensive agent. On day 4, she complained of right-sided neck pain. MRI angiogram revealed a short segment dissection of the right vertebral artery at the C2-3 level. Pregnancy was terminated on the same day with emergency Caesarean Section and anticoagulation was started subsequently. Post-operative recovery was complicated by rectus sheath haematoma requiring evacuation. She was discharged home on Aspirin without any neurological sequelae. Conclusion: Because of collateral circulation, unilateral vertebral artery dissections may go unrecognized and may be more common than suspected. The outcome for most patients is benign, reflecting the adequacy of the collateral circulation in young patients. Spontaneous VAD is usually treated with anticoagulation or antiplatelet therapy for a minimum of 3-6 months to prevent future ischaemic events, allowing the dissection to heal on its own. We had two cases of VAD in the context of hypertensive disorders of pregnancy with an acceptable outcome. A high level of vigilance is required particularly with preeclamptic patients presenting with head/neck pain to allow an early diagnosis. This is as we hypothesize, early and aggressive management of vertebral artery dissection may potentially prevent further complications.

Keywords: eclampsia, preeclampsia, pregnancy, Vertebral Artery Dissection

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Authors: Olga Smilevska Spasova, Katerina Boshkovska, Gorica Popova, Mirjana Popovska

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Introduction: Pneumonia is an infection of the pulmonary parenchyma. HPIV 3 is one of four viruses that is a member of the Paramyxoviridae family designated types 1-4 that have a nonsegmented, single-stranded RNA genome with a lipid-containing envelope. They are spread from the respiratory tract by aerosolized secretions or by direct contact with secretions. Type 3 is endemic and can cause serious illness in immunocompromised patients. Illness caused by parainfluenza occurs shortly after inoculation with the virus. The level of immunoglobulin A antibody in serum is the best predictor of susceptibility to infection. Streptococcus pneumonia or pneumococcus is a Gram-positive, spherical bacteria, usually found in pairs and it is a member of the genus Streptococcus. Streptococcus pneumonia resides asymptomatically in healthy carriers typically colonizing the respiratory tract, sinuses, and nasal cavity. In individuals with weaker immune systems like young infants, pneumococcal bacterium is the most common cause of community-acquired pneumonia in the world. Case Report: The aim is to present a case of lower respiratory tract infection in an infant caused by parainfluenza virus 3, S. pneumonia and undifferentiated gram-negative bacteria that was successfully treated. The infant is with a history of recurrent episodes of wheezing in the past 3mounts.Infant of 10months presents 2weeks before admittance with high fever, runny nose, and cough. The primary pediatrician prescribed oral cefpodoxime for 10days and inhaled salbutamol. Two days before admittance in hospital the infant with high fever, cough, and difficulty breathing. At admittance, infant is pale, anxious with rapid respirations, cough, wheezing and tachycardia. On auscultation: vesicular breathing sounds with high pitched wheezing and on the right coarse crackles. Investigations: Blood analysis: RBC: 4, 7 x1012L, WBC: 8,3x109L: Neut: 42.73% Lym: 41.57%, Hgb: 9.38 g/dl MCV: 62.7fl, MCH: 20.0pg MCHC: 31.8 g/dl RDW: 18.7% Plt-307.9 x109LCRP: 2,5mg/l, serum iron-7.92umol/l, O2sat-97% on blood gas analysis, puls-125/min.X-ray of chest with hyperinflationand right pericardial consolidation. Microbiological analysis of sputum sample is positive for undifferentiated gram-negative bacteria (colonizer)–resistant to cefotaxime, ampicillin, cefoxitin, sulfamet.+trimetoprim and sensitive to amikacin, gentamicin, and ciprofloxacin. Molecular multiplex RT-PCR for 19 viruses and multiplex PCR for 7 bacteria test for respiratory pathogens positive for Parainfluenza virus 3(Ct=22.73), Streptococcus pneumonia (Ct=26.75).IED: IgG-9.31g/l, IgA-0.351g/l, IgM-0.86g/l. Therapy: Treatment was started with inhaled salbutamol, intravenous antibiotic cefotaxime as well as systemic corticosteroids. On day 7 because of slow clinical resolution of chest auscultation findings and an etiologic clue with a positive sputum sample for resistant undifferentiated gram negative bacteria, a second intravenous antibiotic was administered amikacin. The infant is discharged on day 14 with resolution of clinical findings. Conclusion: Mixed co-infections with respiratory viruses and bacteria in immunocompromised infants are likely to lead to a more severe form of community acquired pneumonia that will need hospitalization.

Keywords: HPIV- 3, infant, pneumonia, S. pneumonia, x-ray chest

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

Abstract:

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

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

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

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

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

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