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Introduction Systemic lupus erythematosus (SLE) and sickle cell disease (SCD) are distinct multisystemic diseases that commonly affect blacks. There are few reports of their co-existence in Western literature and a paucity of reports in Sub-Saharan Africa. Their co-existence is associated with diagnostic delay and treatment dilemmas. The aim is to describe the clinical, laboratory, and treatment profile of Nigerian lupus with sickle cell disease. Material and methods A 7-year retrospective descriptive study of lupus patients with sickle cell disease was performed. Medical records of eligible patients were extracted into a proforma, transferred into SPSS, and analyzed with descriptive statistics. Sociodemographic, clinical, laboratory, and treatment data were presented as frequency and percentages. Results Twelve SLE-SCD cases (female 11, male 1) were identified. The mean age was 28.5 years and the mean duration of illness prior to diagnosis was 9.5 years. The median follow-up period was 3.1 years and the common presentations were mucocutaneous (66%), renal, (50%) serositis (33%), and neurological (16%) in decreasing order. All had anemia and positive antinuclear antibody, 33% had pancytopenia and 75% had positive anti-dsDNA and anti-Smith. Two are on maintenance hemodialysis, one with interstitial lung disease, and one on long-term anticoagulation due to deep vein thrombosis. Conclusions Sickle cell disease and SLE should be considered in SCD with atypical clinical and labo­ratory features. We hope this report will raise diagnostic suspicion and prompt early diagnosis and treatment to prevent multiorgan damage that may ensue from such an association.

Context: Simulation-based training is a growing format in healthcare education in Nigeria. So far, most evaluation of the outcome have been limited to the usual pre- and post- tests of knowledge acquisition. Objective: To evaluate our simulation-based airway training, identify the challenges and their potential solutions. Materials and Methods: This study was conducted in the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu in April, 2024; seven months after the maiden simulation-based airway workshop. We applied the 4-level Kirkpatrick model of training evaluation to assess the outcome of the workshop. The attendees of the aforementioned simulation-based airway management workshop were invited as participants for the workshop evaluation. A mixed-method research design encompassing focus-group discussions and questionnaire-based survey was used for data collection. Results: Twenty-nine respondents completed the questionnaire-based survey (six anaesthesia fellows, fifteen residents, eight anaesthetic technicians). Only seventeen respondents (58.6%) have had previous exposure to manikin-based training. The overall satisfaction rating with the SBT was 82.3±11.0 [0-100 scale]. The perceived learning from the SBT was adjudged to be greater in technical skills and knowledge than communication skills. Following the training, the trainees’ behaviour improved with the regular provision and use of gum-elastic bougies during endotracheal intubation. While most participants expressed the desire for more frequent training, some recommended the use of manikins with difficult airway as the means to enhance the SBT. Conclusion: The training positively impacted on the trainees’ learning and behaviour. Most respondents requested more frequent training sessions as the means of enhancing the training

Introduction Five of the neglected tropical diseases use a strategy of preventative chemotherapy distributed via mass drug administration (MDA) for all eligible people living in endemic areas. To be successful, high coverage must be sustained over multiple rounds. Therefore, it will be difficult to reach elimination as a public health problem using MDA if there remain clusters of people who have never been treated. The study aims to explore the reasons why people with high mobility report being never treated during MDA and to provide evidence to support the development of standardised questions for data collection using qualitative research tools.Methods We conducted an exploratory study using qualitative methods among displaced people, nomads/transhumants and economic migrants who self-reported that they had never been treated during MDA in the health districts of Tominian and Kalabancoro in Mali. Data were collected through in-depth individual interviews and focus group discussions. Nvivo V.14 software was used for data management and analysis.Results The main reasons reported for never treatment included: geographical mobility, lack of awareness/information, negative rumours, fear of side effects, conflict and insecurity and logistical difficulties faced in reaching these populations. Proposed solutions included involving communities in the MDA, increasing awareness and information campaigns, effectively managing side effects, and designing and implementing flexible and effective interventions.Conclusion This study highlights that there are people with high mobility who may never have been treated during any round of MDA. The reasons for never treatment highlight the challenges faced when reaching particular groups during MDA activities/interventions. Suggested remedies will require programmes to implement more flexible and tailored interventions. Customised approaches based on the context are essential to guarantee fair access to preventive chemotherapy. Effective interventions must consider the supply and demand side in crafting interventions. This research adds to the evidence base to understand never treatment, particularly among highly mobile population groups and in schistosomiasis elimination programmes.

Abstract Introduction Although an essential frontline service in the prevention of child morbidity and mortality, there are indications that routine vaccinations have been disrupted during the COVID-19 pandemic. The present study aimed to compare vaccination coverage before COVID-19 in Mali in 2019 and during COVID-19 in 2020. Objective To compare vaccination coverages before COVID-19 in Mali in 2019 and during COVID-19 in 2020. Design Cross-sectional study. Setting and participants We collected routine immunization data from 2019 to 2020 of children under one year in the health district of Commune V in Bamako which includes twelve community health centers (CSCom). Results Considering all vaccines together, coverage in 2019 was higher than in 2020 (88.7% vs. 71,6%) (p

ObjectiveThe objective of this proposed scoping review is to identify and map the available evidence on interventions that aim to help informal caregivers identify and/or manage delirium in an older person at home.IntroductionDelirium is a neurocognitive condition characterized by acute confusion and is associated with increased risk of morbidity and mortality. Research estimates delirium to be present in 17% of community-dwellers aged 85 and older, increasing proportionally with age to 45% in those aged 90 and older. Delirium often occurs at the onset of an older person's acute illness or exacerbation of a chronic illness (sometimes while at home) and, because of its protracted nature, usually continues after a hospital stay. Even when an older person's delirium resolves during hospitalization, they remain at risk of its recurrence after discharge home. Consequently, knowing how to detect and manage delirium is critical for informal caregivers of older people at home. However, there are no reviews focused exclusively on this topic in this setting.Inclusion criteriaThe population of interest includes informal caregivers of a person aged 65+. Concepts of interest include delirium detection and/or management interventions. The context of interest is any setting where informal care is delivered, including the transition from hospital to home, in any geographical area.Materials and methodsThe review will be conducted according to the JBI guidelines for scoping reviews. A three-step search strategy will be used to locate both published and unpublished papers in MEDLINE, Embase, CINAHL, PsycINFO, Web of Science Core Collection, ProQuest Nursing & Allied Health, SCOPUS, LILACS, and SciELO, PQD&T, NDLTD, Google Scholar and Google. No language restrictions will be placed on the review. Papers will be screened for eligibility at the title, abstract, and full text level by two independent reviewers. Data will be extracted by two independent reviewers and managed in Covidence. Any disagreements in screening or data extraction will be resolved by consensus or a third reviewer. Results will be summarised in narrative and tabular formats.

IntroductionThere is a pressing need for transitional care that prepares rural dwelling medical patients to identify and respond to the signs of worsening health conditions. An evidence-based warning signs intervention has the potential to address this need. While the intervention is predominantly delivered by nurses, other healthcare providers may be required to deliver it in rural communities where human health resources are typically limited. Understanding the perspectives of other healthcare providers likely to be involved in delivering the intervention is a necessary first step to avert consequences of low acceptability, such as poor intervention implementation, uptake, and effectiveness. This study examined and compared nurses' and other healthcare providers' perceived acceptability of an evidence-based warning signs intervention proposed for rural transitional care.MethodsA cross-sectional design was used. The convenience sample included 45 nurses and 32 other healthcare providers (e.g., physical and occupational therapists, physicians) who self-identified as delivering transitional care to patients in rural Ontario, Canada. In an online survey, participants were presented with a description of the warning signs intervention and completed established measures of intervention acceptability. The measures captured 10 intervention acceptability attributes (effectiveness, appropriateness, risk, convenience, relevance, applicability, usefulness, frequency of current use, likelihood of future use, and confidence in ability to deliver the intervention). Ratings ≥ 2 indicated acceptability. Data analysis included descriptive statistics, independent samples t-tests, as well as effect sizes to quantify the magnitude of any differences in acceptability ratings between nurses and other healthcare providers.ResultsNurses and other healthcare providers rated all intervention attributes > 2, except the attributes of convenience and frequency of current use. Differences between the two groups were found for only three attributes: nurses' ratings were significantly higher than other healthcare providers on perceived applicability, frequency of current use, and the likelihood of future use of the intervention (all p's < .007; effect sizes .58 - .68, respectively).DiscussionThe results indicate that both participant groups had positive perspectives of the intervention on most of the attributes and suggest that initiatives to enhance the convenience of the intervention's implementation are warranted to support its widespread adoption in rural transitional care. However, the results also suggest that other healthcare providers may be less receptive to the intervention in practice. Future research is needed to explore and mitigate the possible reasons for low ratings on perceived convenience and frequency of current use of the intervention, as well as the between group differences on perceived applicability, frequency of current use, and the likelihood of future use of the intervention.ConclusionsThe intervention represents a tenable option for rural transitional care in Ontario, Canada, and possibly other jurisdictions emphasizing transitional care.

South Africa is a carbon-intensive country, with coal dominating the indigenous energy resource base; however, targets have been set to reduce the national carbon emissions. The transition from coal to cleaner sources of energy generation can be encouraged by the administration of new technologies. Hence, the study aims to review research progress on the pyrolysis of water hyacinth as a tool for the smooth transition to low carbon and climate-resilient economy. Water hyacinth is suitable for energy recovery due to its high carbon content and heating value. The outcome shows that pyrolytic products such as liquid, char and non-condensable gas fractions are beneficial. This paper contributes to policy and research deliberations on promoting and adopting pyrolysis technology in addressing South Africa’s energy crisis and water hyacinth invasion.

Despite a significant reduction in the burden of malaria in children under five years-old, the efficient implementation of seasonal malaria chemoprevention (SMC) at large scale remains a major concern in areas with long malaria transmission. Low coverage rate in the unattainable areas during the rainy season, a shift in the risk of malaria to older children and the rebound in malaria incidence after stopping drug administration are mainly reported in these areas. These gaps represent a major challenge in the efficient implementation of SMC measures. An open randomized study was conducted to assess the effect of a fifth additional round to current regime of SMC in older children living in Dangassa, a rural malaria endemic area. Poisson regression Model was used to estimate the reduction in malaria incidence in the intervention group compared to the control group including age groups (5–9 and 10–14 years) and the use of long-lasting insecticidal nets (LLINs; Yes or No) with a threshold at 5%. Overall, a downward trend in participation rate was observed from August (94.3%) to November (87.2%). In November (round 4), the risk of malaria incidence was similar in both groups (IRR = 0.66, 95%CI [0.35–1.22]). In December (round 5), a decrease of 51% in malaria incidence was observed in intervention group compared to control group adjusted for age groups and the use of LLINs (IRR = 0.49, 95%CI [0.26–0.94]), of which 17% of reduction is attributable to the 5th round in the intervention group. An additional fifth round of SMC resulted in a significant reduction of malaria incidence in the intervention group. The number of SMC rounds could be adapted to the local condition of malaria transmission.

ABSTRACT: Background: Little is known about the distribution of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to patients participating in state medical cannabis programs. The Minnesota cannabis program requires third-party testing of products with limited formulations of cannabis for distribution to patients. Objective: To characterize the distribution of cannabis products, their CBD/THC content, and dosing among patients with qualifying conditions. Methods: This is a retrospective analysis of ∼50% of registered users receiving medical cannabis in Minnesota (June 16, 2016, to November 15, 2019). Data included formulation, CBD/THC prescribed doses, and qualifying conditions. The primary end points were calculated using daily dose and duration of use. Comparisons were made for CBD and THC total daily dose dispensed, patient age, and approved product. Nonparametric statistical tests were used (significance was set at p < 0.05). Results: A total of 11,520 patients were listed with 1 qualifying condition. The most common condition was intractable pain (60.0%). Median dispensation duration varied from 53 days (cancer) to 322 days (muscle spasms). Most (≥62.8%) patients across all qualifying conditions received both CBD and THC. Median THC dose was lower in older (≥65 years) compared with younger adults with intractable pain (p < 0.0001) and cancer patients (p = 0.0152), and the same pattern was found CBD dose with seizure (p = 0.0498) patients. For commercial products with Food and Drug Administration indications, the median CBD total daily dose was 86.9% lower than the recommended doses for patients with seizures (Epidiolex: Jazz Pharmaceuticals, Palo Alto CA) and median THC total daily dose was 65.3% (Syndros: Benuvia Manufacturing, Round Rock, TX) or 79.3% lower (Marinol: Banner Pharmacaps, Inc., High Point, NC) for cancer patients. Conclusions: A majority of patients received products containing both CBD and THC. Dosages varied by age group and were lower than recommended for conditions with Food and Drug Administration-approved products. Complex pharmacokinetics of THC and CBD, possible age-related changes in physiology, unknown efficacy, and potential for drug interactions all increase the need for monitoring of patients receiving cannabis products. (Curr Ther Res Clin Exp. 2023; 84:XXX–XXX)

Food is indispensable to the growth and development of the people across the world. It remains first in the affairs of man regardless of one's background. A nation without food will experience poverty, hunger and malnutrition which are inimical to overall growth and development. Food production is the cultivation of plants and rearing of animal as well as preparing them for human consumption. The Food and Agricultural Organization has been preaching the need for the people around the world to be food secured. Consequently, the developed countries have been on the vanguard of food security by putting strong policies in place to achieve it to her citizen. Conversely, in developing countries especially in Africa, food production has been given less attention by the government owing to bad governance that led to the alarming increase in the prices of staple food stuffs which resulted into global food crises starting from 1970s. This paper focuses on Nigeria which her food production is contrary to the global best practices leading to food insecurity in the country and the developed countries have been using food as a global politics against the country that is food in-secured. The paper employed primary and secondary historical research to explore the gargantuan challenges of food production in Nigeria despite her abundance resources to achieve food production for her citizens and for export. The work argues that Nigeria should break away from her dependency syndrome and embark on modern food production for her citizens regardless of interdependency of nations and Ecological Armageddon that threatening the environment. The work concludes that Nigeria needs good leaders that are more proactive to food production rather than politicizing it. The paper recommends that government should synchronize both internal and external remedies of large scale food production to promote food sufficiency that can enhance peace and development in the comity of nations.

Abstract Background Endoplasmic reticulum (ER) stress is a common feature of Parkinson’s disease (PD), and several PD-related genes are responsible for ER dysfunction. Recent studies suggested LRRK2-G2019S, a pathogenic mutation in the PD-associated gene LRRK2, cause ER dysfunction, and could thereby contribute to the development of PD. It remains unclear, however, how mutant LRRK2 influence ER stress to control cellular outcome. In this study, we identified the mechanism by which LRRK2-G2019S accelerates ER stress and cell death in astrocytes. Methods To investigate changes in ER stress response genes, we treated LRRK2-wild type and LRRK2-G2019S astrocytes with tunicamycin, an ER stress-inducing agent, and performed gene expression profiling with microarrays. The XBP1 SUMOylation and PIAS1 ubiquitination were performed using immunoprecipitation assay. The effect of astrocyte to neuronal survival were assessed by astrocytes-neuron coculture and slice culture systems. To provide in vivo proof-of-concept of our approach, we measured ER stress response in mouse brain. Results Microarray gene expression profiling revealed that LRRK2-G2019S decreased signaling through XBP1, a key transcription factor of the ER stress response, while increasing the apoptotic ER stress response typified by PERK signaling. In LRRK2-G2019S astrocytes, the transcriptional activity of XBP1 was decreased by PIAS1-mediated SUMOylation. Intriguingly, LRRK2-GS stabilized PIAS1 by increasing the level of small heterodimer partner (SHP), a negative regulator of PIAS1 degradation, thereby promoting XBP1 SUMOylation. When SHP was depleted, XBP1 SUMOylation and cell death were reduced. In addition, we identified agents that can disrupt SHP-mediated XBP1 SUMOylation and may therefore have therapeutic activity in PD caused by the LRRK2-G2019S mutation. Conclusion Our findings reveal a novel regulatory mechanism involving XBP1 in LRRK2-G2019S mutant astrocytes, and highlight the importance of the SHP/PIAS1/XBP1 axis in PD models. These findings provide important insight into the basis of the correlation between mutant LRRK2 and pathophysiological ER stress in PD, and suggest a plausible model that explains this connection.

Summary: Although it is reported that mitochondria-localized nuclear transcription factors (TFs) regulate mitochondrial processes such as apoptosis and mitochondrial transcription/respiration, the functions and mechanisms of mitochondrial dynamics regulated by mitochondria-localized nuclear TFs are yet to be fully characterized. Here, we identify STAT6 as a mitochondrial protein that is localized in the outer membrane of mitochondria (OMM). STAT6 in OMM inhibits mitochondrial fusion by blocking MFN2 dimerization. This implies that STAT6 has a critical role in mitochondrial dynamics. Moreover, mitochondrial accumulation of STAT6 in response to hypoxic conditions reveals that STAT6 is a regulator of mitochondrial processes including fusion/fission mechanisms.

Visual-spatial is needed to improve submicroscopic understanding, such as polar and nonpolar covalent bonding materials. Not many 3D interactive multimedia have been developed with visual-spatial orientation. This research aims to produce 3D interactive multimedia with spatial-visual orientation on polar and nonpolar covalent bond materials suitable for use. The research design uses an R&D (Research and Development) research model developed but restricted to a limited trial step. The eligibility criteria include validity (content and construct) and practicality. The validity criteria are based on the results of the validity assessment data from three validators. Practicality criteria are based on the assessment given by three chemistry teachers shortly after the visual-spatial-oriented 3D interactive multimedia trial. Overall data were analyzed descriptive- quantitatively. The results of the study concluded that the developed 3D interactive multimedia meets the eligibility requirements. Each validation indicator in 3D interactive multimedia receives an assessment from the validator with mode (Mo) at least 4 in the score range 1-5 and the percentage of agreement (R) between validators above 75%. The 3D interactive multimedia meets practicality requirements because each indicator receives an assessment from the user students with (Mo) at least 4 in the score range 1-5. The percentage of agreement (R) between user students is above 75%.

Abstract Brain injury causes astrocytes to become reactive (astrogliosis). In this study, we compared astrogliosis in acutely injured cortex and striatum of adult FVB/N mice induced by stereotaxic injection of ATP, a component of danger-associated molecular patterns (DAMPs). Interestingly, MR analysis showed that same amount of ATP induced smaller damage in the cortex than in the striatum. However, in histological analysis, thick and dense scar-like astrogliosis was found in the injured cortex near meninges within 2 wk., but not in other regions, including the striatum and even the cortex near the corpus callosum for up to 30 d. There was little regional difference in the number of Ki67(+)-proliferating astrocytes or mRNA expression of inflammatory cytokines. The most prominent difference between regions with and without scar-like astrogliosis was blood vessel formation. Blood vessels highly expressing collagen 1A1 formed densely near meninges, and astrocytes converged on them. In other regions, however, both blood vessels and astrocytes were relatively evenly distributed. Consistent with this, inhibition of blood vessel formation with the vascular endothelial growth factor (VEGF)-blocking antibody, Avastin, attenuated scar-like astrogliosis near meninges. These results indicate that region-specific astrogliosis occurs following brain injury, and that blood vessel formation plays a critical role in scar formation.

Abstract The presence of heavy metals in polluted water is known not only to cause severe harm to marine organisms, but also to terrestrial plants and animals including human beings. This research applied low-cost and environmentally benign adsorbent primed from waste orange peel (OP) for the removal of Cd(II) ions from aqueous solution via batch adsorption process. The surface properties of the orange peel powder were studied using scanning electron microscopy (SEM), X-ray spectroscopy (XRD) and Fourier transform infrared spectroscopy (FT-IR). Operational conditions like temperature, contact time, sorbent dosage, solution pH and initial adsorbate concentration were investigated. The utmost uptake of Cd(II) ion was obtained at a contact time of 120 min, initial metal concentration of 240 mg/L, adsorbent dosage of 0.04 g/L, temperature of 45 °C and solution pH of 5.5. Equilibrium results showed that the orange peel adsorbent has an adsorption capacity of 128.23 mg/g as obtained from the Langmuir isotherm. The adsorption kinetics data followed a pseudo-first-order kinetic model with correlation coefficient (R2) > 0.9 and low standard % error values. The adsorption process was found to be endothermic in nature with enthalpy of 0.0046 kJ mol−1 and entropy of-636.865 Jmol−1K−1. Results from the optimization study indicated that higher adsorbent dosage and lower Cd(II) ion concentration increased the percentage of Cd(II) ion removal. Thus, orange peel could be used in the removal of Cd(II) ion from aqueous solutions.

In developing African countries, a considerable body of knowledge exists about the evolving stages of corporate social responsibility (CSR) practices from mere philanthropic actions to damage control strategy, especially in the mining sector. However, little is known about the emerging strategic CSR as a competitive strategy particularly its dimensional outcomes among diverse sectors in the region. Applying a multidimensional perspective of corporate social responsibility activities, we explored how customers’ perception of a firm’s economic, legal, ethical, and social responsibility actions influence the firm’s product rating, consumer loyalty, and firms’ strategic legitimacy among telecoms subscribers in Nigeria. A probability sampling technique was used to select 126 subscribers with a proportionate representation of the five mobile phone service providers in Nigeria. From the collected data, descriptive statistics were applied to analyze the demographic profile of the participants while the partial least squares structural equation modeling (PLS-SEM) was used to test the hypotheses. Contrary to expectations, the outcomes suggest that consumer perception of telecoms firms’ economic responsibilities has no significant positive influence on the firms’ product rating, consumer loyalty, and the firms’ strategic legitimacy. Conversely, the outcomes support our propositions that the consumer perception of telecoms firms’ social, legal, and ethical responsibility actions has a significant positive influence on the firms’ product rating, consumer loyalty, and firms’ strategic legitimacy. The findings suggest the need for telecoms firms to focus on social, legal, and ethical responsibility dimensions as competitive strategies.

Objetivos: As ligas acadêmicas têm uma irrefutável importância na formação dos estudantes de medicina, uma vez que oferecem aulas ministradas por especialistas, oportunidade de produção científica e extensão com contato com a população. Por esse motivo, é importante uma análise do perfil das ligas de hematologia do Brasil, para permitir o entendimento da estrutura das ligas e poder auxiliar na identificação de seus maiores desafios, em busca de possíveis soluções. Material e métodos: Foi realizada uma pesquisa quantitativa, através da aplicação de questionários online. A população alvo eram as ligas acadêmicas de hematologia do Brasil. No ano de 2020 foram abordadas 44 ligas, a taxa de resposta foi de 72,7%, totalizando 32 ligas. O instrumento era autoaplicável anônimo, e a participação voluntária, com assinatura do Termo de Consentimento Livre e Esclarecido (TCLE). Esta pesquisa foi aprovada pelo comitê de ética da instituição proponente sob o Caae 24510719.2.0000.0029. Para este trabalho foram analisadas 9 questões, das 13 contidas no questionário, versando sobre as características, atividades e projetos de cada liga acadêmica participante. Os dados foram analisados utilizando-se o office for windows 10, pela ferramenta Excel 2013, para análise descritiva. As variáveis foram expressas em frequências absolutas e relativas. Para toda e qualquer análise, os dados foram codificados, de forma a garantir o sigilo dos participantes. Resultados: Quanto à fundação, a maioria das ligas foi fundada entre 2015 e 2020. E 40,6% das ligas possuem mais de 20 ligantes. Em relação ao processo seletivo, 78,12% das ligas realizam o processo anualmente e 18,75% semestralmente. No pilar da pesquisa 50% publicam trabalhos ao menos 1 a 3 vezes por semestre, 9,37% publicam mais de 10 vezes. As reuniões de ensino são realizadas de forma quinzenal em 50% das ligas e mensal em 34,37%. Quanto à extensão, a maioria possui projeto de extensão – 75%, os resultados apontam que 71,87% das ligas afirmam ter algum tipo de dificuldade no desenvolvimento dos projetos. Apenas 6,25% das ligas não possuem orientador Hematologista e a maioria possui ligantes assíduos (90,62%). Discussão: A fundação recente, somada à quantidade crescente de ligantes pode indicar um recente aumento do interesse dos estudantes pela especialidade de hematologia. é possível observar que as ligas cumprem o tripé universitário de forma exemplar: mais da metade das ligas cumpre o tripé ensino-pesquisa-extensão, oferecendo aos ligantes a oportunidade de aprofundamento do conhecimento em hematologia, bem como a chance de publicação em congressos, incentivo à pesquisa e desenvolvimento de atividades junto à população. Sendo a extensão uma atividade de difícil desenvolvimento, é importante destacar a grande quantidade de ligas que apresentam alguma dificuldade, sendo este o ponto que mais necessita de apoio. Conclusão: A partir dos dados observados é possível notar que apesar de fundadas recentemente, as ligas acadêmicas de hematologia mantêm atividades de ensino, estimulam a publicação de trabalhos, valorizam pesquisa e têm nas atividades extensionistas seu maior desafio, sendo necessária uma análise especìfica das principais dificuldades enfrentadas. A grande presença de orientadores hematologistas nas ligas se mostra como um bom preditor de desenvolvimento futuro.

Introdução e objetivos: As ligas acadêmicas são entidades estudantis que proporcionam o contato direto do aluno com a comunidade em que ele vive, por meio de projetos de extensão, pesquisa e ensino. Elas promovem a expansão do conhecimento intelectual teórico-prático para além da universidade. O tripé: extensão, pesquisa e ensino permite o desenvolvimento de um aprendizado reflexivo e criativo para a consolidação do conhecimento apreendido nas salas de aula (Azevedo et al, 2018). Assim, o objetivo deste trabalho foi analisar seu funcionamento nas Ligas Acadêmicas de Hematologia do Brasil. Métodos: Foi realizada uma pesquisa quantitativa, através da aplicação de questionários online. A população alvo eram as ligas acadêmicas de hematologia do Brasil. No ano de 2020 foram abordadas 44 ligas, a taxa de resposta foi de 72,7%. O instrumento era autoaplicável anônimo, e a participação voluntária, com assinatura do Termo de Consentimento Livre e Esclarecido (TCLE). Esta pesquisa foi aprovada pelo comitê de ética da instituição proponente sob o Caae 24510719.2.0000.0029. Para este trabalho foram analisadas 6 questões, das 13 contidas no questionário, versando sobre o tripé universitário. Os dados foram analisados pela ferramenta Excel 2013, para análise descritiva e foram codificados, de forma a garantir o sigilo dos participantes. Resultados: Na área de pesquisa, 50% das ligas publicam de 1 a 3 trabalhos por semestre; 18,8% 4 a 6 trabalhos, porém, 21,9% não publicam em congressos. Quanto às reuniões de ensino, 50% são quinzenais; 34,4% mensais; 90.6% afirmam ter ligantes assíduos. Em relação à extensão, 75% possuem atividade de extensão e, dentre elas, 83,3% possuem contato com a população. Quanto às dificuldades enfrentadas na extensão, 3,1% afirmam não ter adesão dos estudantes; 12,5% enfrentam dificuldade em encontrar professores hematologistas para auxiliar; 9,4% em elaborar um projeto de extensão na área de hematologia; 28,1% não enfrentam dificuldade. Discussão: As atividades de ensino proporcionam a oportunidade de contato com conteúdos aprofundados em áreas de interesse e convivência com profissionais da área. Além da oportunidade de preencher carências do currículo formal, portanto, é fundamental que as ligas mantenham o pilar do ensino e a assiduidade dos ligantes. Segundo Neves (2008), ao vivenciar áreas de pesquisa, os estudantes tornam-se potencialmente melhores profissionais, devido à ampliação da visão crítica e aumento do poder reflexivo, afetando positivamente o desempenho profissional e o aprendizado de se expressar baseado em informações sólidas. Os projetos extensionistas promovem uma aproximação entre os ligantes e a comunidade, permitindo, assim, acesso aos determinantes sociais que permeiam o binômio saúde-doença. Além disso, as atividades extensionistas contribuem para uma melhor compreensão do funcionamento da saúde pública, a partir das diferentes realidades vivenciadas, de modo a preparar os estudantes para atuar reconhecendo as necessidades da população (COSTA et al., 2017). Conclusão: Embora em muitas universidades as ligas estejam vinculadas às Pró-Reitorias de Extensão e, teoricamente, sejam norteadas pelo tripé ensino, pesquisa e extensão, há predominância das práticas de ensino e de pesquisa sobre a extensão, possivelmente devido à burocracia na criação das Ligas, ao calendário acadêmico e ao distanciamento entre a universidade e a comunidade.

This research examined the effects of monetary and fiscal policies on stock returns in Nigeria. The researchers utilized ex-post facto research design using the time series data of the annual market values of All Share Index (ASI) of the Nigerian Stock Exchange (NSE). It was yearly data on the various monetary policy and fiscal policy variables obtained from the Central Bank of Nigeria Statistical Bulletins covering from 1985 to 2017. The result of the cointegration test reveals a long-run relationship between monetary variables and stock returns. Meanwhile, the overall result shows that monetary policy has a significant effect on stock return. However, there is no long-run relationship between fiscal policy variables and stock returns. Meanwhile, the result of the Unrestricted Vector Autoregression model shows that fiscal policy has a significant effect on stock prices in Nigeria. On the other hand, a long-run relationship exists between monetary policy, fiscal policy, and stock returns. It has a significant effect on stock returns in Nigeria. This implies that monetary and fiscal policies have a significant effect on stock returns in Nigeria. It is recommended that there is a need for the federal government to harmonize fiscal and monetary policies in the same direction and to equally design policies that promote a free market for the growth of the Nigerian economy.

Abstract Multifunctional signal transducer and activator of transcription (STAT) proteins play important roles in cancer. Here, we have shown that STAT6 is epigenetically silenced in some cases of malignant glioblastoma, which facilitates cancer cell survival in a hypoxic microenvironment. This downregulation results from hypermethylation of CpG islands within the STAT6 promoter by DNA methyltransferases. STAT6 interacts with Rheb under hypoxia and inhibits mTOR/S6K/S6 signaling, in turn, inducing increased HIF-1α translation. STAT6 silencing and consequent tumor-promoting effects are additionally observed in glioma stem-like cells (GSC). Despite recent advances in cancer treatment, survival rates have shown little improvement. This is particularly true in the case of glioma, where multimodal treatment and precision medicine is needed. Our study supports the application of epigenetic restoration of STAT6 with the aid of DNA methyltransferase inhibitors, such as 5-aza-2-deoxycytidine, for treatment of STAT6-silenced gliomas.

Dysfunctional regulation of inflammation may contribute to the progression of neurodegenerative diseases. The results of this study revealed that DJ-1, a Parkinson's disease (PD) gene, regulated expression of prostaglandin D2 synthase (PTGDS) and production of prostaglandin D2 (PGD2), by which DJ-1 enhanced anti-inflammatory function of astrocytes. In injured DJ-1 knockout (KO) brain, expression of tumor necrosis factor-alpha (TNF-α) was more increased, but that of anti-inflammatory heme oxygenase-1 (HO-1) was less increased compared with that in injured wild-type (WT) brain. Similarly, astrocyte-conditioned media (ACM) prepared from DJ-1-KO astrocytes less induced HO-1 expression and less inhibited expression of inflammatory mediators in microglia. With respect to the underlying mechanism, we found that PTGDS that induced expression of HO-1 was lower in DJ-1 KO astrocytes and brains compared with their WT counterparts. In addition, PTGDS levels increased in the injured brain of WT mice, but barely in that of KO mice. We also found that DJ-1 regulated PTGDS expression through Sox9. Thus, Sox9 siRNAs reduced PTGDS expression in WT astrocytes, and Sox9 overexpression rescued PTGDS expression in DJ-1 KO astrocytes. In agreement with these results, ACM from Sox9 siRNA-treated astrocytes and that from Sox9-overexpression astrocytes exerted opposite effects on HO-1 expression and anti-inflammation. These findings suggest that DJ-1 positively regulates anti-inflammatory functions of astrocytes, and that DJ-1 dysfunction contributes to the excessive inflammatory response in PD development.

Abstract Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a common feature of Parkinson’s disease (PD) and further suggests that several PD-related genes are responsible for ER dysfunction. However, the underlying mechanisms are largely unknown. Here, we defined the mechanism by which LRRK2-G2019S (LRRK2-GS), a pathogenic mutation in the PD-associated gene LRRK2, accelerates ER stress and cell death. Treatment of cells with α-synuclein increased the expression of ER stress proteins and subsequent cell death in LRRK2-GS astrocytes. Intriguingly, we found that LRRK2-GS localizes to the ER membrane, where it interacts with sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and suppress its activity by preventing displacement of phospholamban (PLN). LRRK2-GS–mediated SERCA malfunction leads to ER Ca2+ depletion, which induces the formation of mitochondria-ER contacts and subsequent Ca2+ overload in mitochondria, ultimately resulting in mitochondrial dysfunction. Collectively, our data suggest that, in astrocytes, LRRK2-GS impairs ER Ca2+ homeostasis, which determines cell survival, and as a result, could contribute to the development of PD.

BackgroundIn Mali, cutaneous leishmaniasis (CL) and filariasis are co-endemic. Previous studies in animal models of infection have shown that sand fly saliva enhance infectivity of Leishmania parasites in naïve hosts while saliva-specific adaptive immune responses may protect against cutaneous and visceral leishmaniasis. In contrast, the human immune response to Phlebotomus duboscqi (Pd) saliva, the principal sand fly vector in Mali, was found to be dichotomously polarized with some individuals having a Th1-dominated response and others having a Th2-biased response. We hypothesized that co-infection with filarial parasites may be an underlying factor that modulates the immune response to Pd saliva in endemic regions.Methodology/principal findingsTo understand which cell types may be responsible for polarizing human responses to sand fly saliva, we investigated the effect of salivary glands (SG) of Pd on human monocytes. To this end, elutriated monocytes were cultured in vitro, alone, or with SG, microfilariae antigen (MF ag) of Brugia malayi, or LPS, a positive control. The mRNA expression of genes involved in inflammatory or regulatory responses was then measured as were cytokines and chemokines associated with these responses. Monocytes of individuals who were not exposed to sand fly bites (mainly North American controls) significantly upregulated the production of IL-6 and CCL4; cytokines that enhance leishmania parasite establishment, in response to SG from Pd or other vector species. This selective inflammatory response was lost in individuals that were exposed to sand fly bites which was not changed by co-infection with filarial parasites. Furthermore, infection with filarial parasites resulted in upregulation of CCL22, a type-2 associated chemokine, both at the mRNA levels and by its observed effect on the frequency of recruited monocytes.Conclusions/significanceTogether, our data suggest that SG or recombinant salivary proteins from Pd alter human monocyte function by upregulating selective inflammatory cytokines.

Abstract Background Filariasis and leishmaniasis are two neglected tropical diseases in Mali. Due to distribution and associated clinical features, both diseases are of concern to public health. The goal of this study was to determine the prevalence of co-infection with filarial (Wuchereria bancrofti and Mansonella perstans) and Leishmania major parasites in two ecologically distinct areas of Mali, the Kolokani district (villages of Tieneguebougou and Bougoudiana) in North Sudan Savanna area, and the district of Kolondieba (village of Boundioba) in the South Sudan Savanna area. Methods The prevalence of co-infection (filarial and Leishmania) was measured based on (i) Mansonella perstans microfilaremia count and/or filariasis immunochromatographic test (ICT) for Wuchereria bancrofti-specific circulating antigen, and (ii) the prevalence of delayed type hypersensitivity (DTH) responses to Leishmania measured by leishmanin skin test (LST). Results In this study, a total of 930 volunteers between the age of 18 and 65 were included from the two endemic areas of Kolokani and Kolondieba. In general, in both areas, filarial infection was more prevalent than Leishmania infection with an overall prevalence of 15.27% (142/930) including 8.7% (81/930) for Mansonella perstans and 8% (74/930) for Wuchereria bancrofti-specific circulating antigen. The prevalence of Leishmania major infection was 7.7% (72/930) and was significantly higher in Tieneguebougou and Bougoudiana (15.05%; 64/425) than in Boundioba (2.04%; 8/505) (χ2 = 58.66, P

Summary: Recent evidence of prion-like propagation of α-synuclein (α-syn) into neighboring neurons set up a paradigm to elucidate the mechanism of progression of Parkinson’s disease (PD) and to develop therapeutic strategies. Here, we show that FcγRIIB expressed in neurons functions as a receptor for α-syn fibrils and mediates cell-to-cell transmission of α-syn. SHP-1 and 2 are activated downstream by α-syn fibrils through FcγRIIB and play an important role in cell-to-cell transmission of α-syn. Also, taking advantage of a co-culture system, we show that cell-to-cell transmission of α-syn induces intracellular Lewy body-like inclusion body formation and that the FcγRIIB/SHP-1/2 signaling pathway is involved in it. Therefore, the FcγRIIB-SHP-1/-2 signaling pathway may be a therapeutic target for the progression of PD. The in vitro system is an efficient tool for further high-throughput screening that can be used for developing a therapeutic intervention in PD. : Prion-like propagation of α-synuclein (α-syn) may contribute to the progression of Parkinson’s disease. Choi et al. demonstrate that FcγRIIB functions as a receptor for α-syn fibrils and that the FcγRIIB-SHP-1/2 signaling pathway mediates cell-to-cell transmission of α-syn. Blocking this signaling pathway attenuates transmission, suppressing Lewy body-like inclusion body formation. Keywords: α-synuclein, cell-to-cell transmission, FcγRIIB, SHP-1, SHP-2

OBJECTIVES/GOALS: Allopregnanolone (ALLO), a modulator of GABAA receptors, may be useful as a treatment for human and canine benzodiazepine-refractory status epilepticus (SE). Our objective was to develop a phamacokinetic-pharmacodynamic (PKPD) model relating ALLO plasma concentrations to electroencephalographic (EEG) effects in dogs. METHODS/STUDY POPULATION: Four healthy dogs and one dog with epilepsy that had implanted intracranial electrodes were utilized. ALLO doses ranging from 1-6 mg/kg were administered IV over 5 min. EEG data were collected during four IM doses (1-2 mg/kg). Blood samples were collected up to 6 hr following dosing. ALLO concentrations were measured using HPLC-MS/MS. Power density was determined in EEG bands using a custom algorithm. A two-compartment link PKPD model was developed to describe the relation between ALLO plasma concentration and change in EEG power in the alpha, beta, delta and theta bands. RESULTS/ANTICIPATED RESULTS: ALLO caused a rapid increase in absolute power density in all EEG bands measured (1-4, >4 – 8, >8 – 12, >12 – 25, and >25 – 100 Hz). The onset of effect was rapid (1-3 min) and demonstrated by frequency band and dose analysis. Concentration-EEG data were best fit by a two-compartment PK model and sigmoidal Emax PD indirect link model. The beta frequency band was most sensitive, showing increases in power at the lowest ALLO concentrations. The EC50 concentration for the beta frequency was ~270 ng/mL. The EC50 values for effects on the other frequency bands were ~500-700 ng /mL. In conclusion, IV ALLO causes a rapid effect on EEG that can be used to determine minimal plasma concentrations associated with target engagement. DISCUSSION/SIGNIFICANCE OF IMPACT: Dose selection for future clinical trials will use the effective concentrations determined here in conjunction with studies in animal status epilepticus models. Studies are planned in client owned dogs with epilepsy to evaluate clinical efficacy in dogs and as nonclinical proof-of-concept evidence supporting translational studies in people. CONFLICT OF INTEREST DESCRIPTION: Michael Rogawski and Dorota Zolkowska are named as inventors on patent applications claiming use of neuroactive steroids including allopregnanolone and ganaxolone in the treatment of status epilepticus.

Tunji S Oluleye,1 Adekunle O Rotimi-Samuel,2 Adetunji Adenekan,2 Olubanke T Ilo,2 Folashade B Akinsola,2 Adeola O Onakoya,2 Olufisayo T Aribaba,2 Adebukunola Adefule-Ositelu,2 Kareem O Musa,2 Yele Oyefeso2 1Retina and Vitreous Unit, Department of Ophthalmology, University College Hospital, Ibadan, 2Department of Ophthalmology, Guinness Eye Center, Lagos University Teaching Hospital, Lagos, Nigeria Abstract: Vogt–Koyanagi–Harada’s (VKH) disease has been reported to be rare in sub-Saharan Africa. Two Nigerians with the disease are presented in this report. The first patient, a 32-year-old pregnant Nigerian woman presented with a 1-month history of bilateral blurring of vision, persistent headache, and alopecia. Presenting visual acuity was 1 m counting fingers in both eyes. Examination revealed vitiligo and poliosis with bilateral panuveitis as well as bilateral exudative retinal detachment. A clinical assessment of complete VKH disease was made. The patient commenced systemic and topical steroids that resulted in remarkable recovery of vision and control of inflammation. The second patient, a 56-year-old Nigerian woman presented with severe headache, tinnitus, and visual loss in both eyes of 2 weeks duration. There was associated redness of both eyes and photophobia. Examination showed visual acuity of Hand motion (HM) and counting fingers at 1 meter (CF). in the right and left eye, respectively, with bilateral panuveitis and bilateral exudative retinal detachment. Subsequent follow-up showed poliosis, vitiligo, and sunsetting fundus appearance. The patient improved with systemic and topical corticosteroids. Developing a high index of suspicion is necessary in diagnosing VKH disease, even in sub-Saharan Africa. Prompt institution of appropriate treatment prevents blindness. Keywords: Vogt–Koyanagi–Harada’s disease, exudative retinal detachment, vitiligo, ­sub-Saharan Africa

Introduction: Spinal muscular atrophy (SMA) and sporadic amyotrophic lateral sclerosis (SALS) are both motor neuron disorders. SMA results from the deletion of the survival motor neuron (SMN) 1 gene. High or low SMN1 copy number and the absence of SMN2 have been reported as risk factors for the development or severity of SALS. Objective: To investigate the role of SMN gene copy number in the onset and severity of SALS in Malians. Material and Methods: We determined the SMN1 and SMN2 copy number in genomic DNA samples from 391 Malian adult volunteers, 120 Yoruba from Nigeria, 120 Luyha from Kenya and 74 U.S. Caucasians using a Taqman quantitative PCR assay. We evaluated the SALS risk based on the estimated SMA protein level using the Veldink formula (SMN1 copy number + 0.2∗SMN2 copy number). We also characterized the disease natural history in 15 ALS patients at the teaching hospital of Point G, Bamako, Mali. Results: We found that 131 of 391 (33.5%) had an estimated SMN protein expression of ≤2.2; 60 out of 391 (15.3%) had an estimated SMN protein expression

BACKGROUND:Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets. The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units (EU) to assess its performance as an integrated surveillance tool for elimination of lymphatic filariasis (LF) and onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS:A cross sectional survey with SD Bioline Onchocerciasis/LF IgG4 Rapid Test was piggy-backed onto a transmission assessment survey (TAS) (using the immunochromatographic card test (ICT) Binax Filariasis Now test for filarial adult circulating antigen (CFA) detection) for LF in Mali among 6-7 year old children in 2016 as part of the TAS in two EUs namely Kadiolo-Kolondieba in the region of Sikasso and Bafoulabe -Kita-Oussoubidiagna-Yelimane in the region of Kayes. In the EU of Kadiolo- Kolondieba, of the 1,625 children tested, the overall prevalence of W. bancrofti CFA was 0.62% (10/1,625) [CI = 0.31-1.09]; while that of IgG4 to Wb123 was 0.19% (3/1,600) [CI = 0.04-0.50]. The number of positives tested with the two tests were statistically comparable (p = 0.09). In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of W. bancrofti CFA was 0% (0/1,700) and that of Wb123 IgG4 antibody was 0.06% (1/1,700), with no statistically significant difference between the two rates (p = 0.99). In the EU of Kadiolo- Kolondieba, the prevalence of Ov16-specific IgG4 was 0.19% (3/1,600) [CI = 0.04-0.50]. All 3 positives were in the previously O. volvulus-hyperendemic district of Kolondieba. In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of Ov16-specific IgG4 was 0.18% (3/1,700) [CI = 0.04-0.47]. These 3 Ov16 IgG4 positives were from previously O.volvulus-mesoendemic district of Kita. CONCLUSIONS/SIGNIFICANCE:The SD Bioline Onchocerciasis/LF IgG4 Rapid test appears to be a good tool for integrated exposure measures of LF and onchocerciasis in co-endemic areas.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Although the etiology of PD has not yet been fully understood, accumulating evidence indicates that neuroinflammation plays a critical role in the progression of PD. α-Synuclein (α-Syn) has been considered to be a key player of the pathogenesis of PD, and recent reports that prion-like propagation of misfolded α-syn released from neurons may play an important role in the progression of PD have led to increased attention to the studies elucidating the roles of extracellular α-syn in the CNS. Extracellular α-syn has also been reported to regulate microglial inflammatory response. In this study, we demonstrated that aggregated α-syn inhibited microglial phagocytosis by activating SHP-1. SHP-1 activation was also observed in A53T α-syn transgenic mice. In addition, aggregated α-syn bound to FcγRIIB on microglia, inducing SHP-1 activation, further inhibiting microglial phagocytosis. Aggregated α-syn upregulated FcγRIIB expression in microglia and upregulated FcγRIIB was also observed in A53T α-syn transgenic mice. These data suggest that aggregated α-syn released from neurons dysregulates microglial immune response through inhibiting microglial phagocytosis, further causing neurodegeneration observed in PD. The interaction of aggregated α-syn and FcγRIIB and further SHP-1 activation can be a new therapeutic target against PD.

Soft drinks are consumed daily in Nigeria due to its affordability, characteristic taste, and thirst quenching potential. However, the high demand may compromise the quality of production with possible contamination of heavy metals which have shown to cause intoxication and death in humans. This study evaluated some constituents of twenty-six soft drinks in Nigeria and investigated the presence of some heavy metal contaminants. The soft drinks were screened for the presence of sugar, carbon dioxide, phosphate and alcohol as well as the pH and acidity determined. The level of cadmium, mercury and lead were determined using atomic absorption spectrophotometer. The study showed the presence of sugar, carbon dioxide, phosphate, and alcohol in the soft drinks. The soft drinks were acidic in nature, pH ranging from 3 to 5 with a mean of 3.6 and the acid concentration was relatively low between 3 and 12 g/L with a mean of 8.1 g/L. Lead was present in all the samples ranging from 0.17 to 3.39 mg/L with a mean of 0.8, mercury was present in 22 samples ranging from 0.29 to 11.32 mg/L with a mean of 2.08 mg/L while cadmium was present only in one sample (0.149 mg/L). When compared to EPA, WHO and NIS standards, the levels of the heavy metal contaminants were above the tolerated limits for good quality drinking water in most samples. These results suggest that soft drinks in Nigeria may be contaminated with heavy metals which constitute a major public health problem. Thus, quality control is recommended during the production process especially at the stages of sterilization and purification.

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder caused by the death of dopaminergic neurons in the substantia nigra. Importantly, altered astrocyte and microglial functions could contribute to neuronal death in PD. In this study, we demonstrate a novel mechanism by which DJ-1 (PARK7), an early onset autosomal-recessive PD gene, negatively regulates inflammatory responses of astrocytes and microglia by facilitating the interaction between STAT1 and its phosphatase, SHP-1 (Src-homology 2-domain containing protein tyrosine phosphatase-1). Astrocytes and microglia cultured from DJ-1-knockout (KO) mice exhibited increased expression of inflammatory mediators and phosphorylation levels of STAT1 (p-STAT1) in response to interferon-gamma (IFN-γ) compared to cells from wild-type (WT) mice. DJ-1 deficiency also attenuated IFN-γ-induced interactions of SHP-1 with p-STAT1 and STAT1, measured 1 and 12 h after IFN-γ treatment, respectively. Subsequent experiments showed that DJ-1 directly interacts with SHP-1, p-STAT1, and STAT1. Notably, DJ-1 bound to SHP-1 independently of IFN-γ, whereas the interactions of DJ-1 with p-STAT1 and STAT1 were dependent on IFN-γ. Similar results were obtained in brain slice cultures, where IFN-γ induced much stronger STAT1 phosphorylation and inflammatory responses in KO slices than in WT slices. Moreover, IFN-γ treatment induced neuronal damage in KO slices. Collectively, these findings suggest that DJ-1 may function as a scaffold protein that facilitates SHP-1 interactions with p-STAT1 and STAT1, thereby preventing extensive and prolonged STAT1 activation. Thus, the loss of DJ-1 function may increase the risk of PD by enhancing brain inflammation.

Barriers to developing treatments for human status epilepticus (SE) include the inadequacy of experimental animal models. In contrast, naturally-occurring canine epilepsy is similar to the human condition and can serve as a platform to translate research from rodents to humans. The objectives of this study were to characterize the pharmacokinetics (PK) of an intravenous (IV) dose of topiramate (TPM) in dogs with epilepsy, and evaluate its effect on intracranial electroencephalographic (iEEG) features. Five dogs with naturally occurring epilepsy were used for this study. Three were getting at least one antiseizure drug as maintenance therapy including phenobarbital (PB). Four (ID 1-4) were used for the 10 mg/kg IV TPM + PO TPM study, and three (ID 3-5) were used for the 20 mg/kg IV TPM study. IV TPM was infused over 5 minutes at both doses. The animals were observed for vomiting, diarrhea, ataxia, and lethargy. Blood samples were collected at scheduled pre- and post-dose times. Plasma concentrations were measured using a validated HPLC-MS method. Non-compartmental and population compartmental modeling were performed (Phoenix WinNonLin and NLME) using plasma concentrations from all dogs in the study. Intracranial EEG (iEEG) was acquired in one dog. The difference between averaged iEEG energy levels at 15 minutes pre- and post-dose was assessed using a Kruskal-Wallis test. No adverse events were noted. Topiramate concentration-time profiles were best fit by a two-compartment model. PB co-administration was associated with a 5.6 fold greater clearance and a ~4 fold shorter elimination half-life. iEEG data showed that TPM produced a significant energy increase at frequencies >4 Hz across all 16 electrodes within 15 minutes of dosing. Simulations suggested that dogs on an enzyme inducer would require 25 mg/kg, while dogs on non-inducing drugs would need 20 mg/kg to attain the target concentration (20-30 µg/mL) at 30-minutes post-dose.This study shows that IV TPM has a relatively rapid onset of action, loading doses appear safe, and the presence of PB necessitates a higher dose to attain targeted concentrations. Consequently, it is a good candidate for further evaluation for treatment of seizure emergencies in dogs and people.

Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas.4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and "other signs/symptoms"). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone.These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended.ClinicalTrials.gov; NCT01586169.

LRRK2, a Parkinson's disease associated gene, is highly expressed in microglia in addition to neurons; however, its function in microglia has not been evaluated. Using Lrrk2 knockdown (Lrrk2-KD) murine microglia prepared by lentiviral-mediated transfer of Lrrk2-specific small inhibitory hairpin RNA (shRNA), we found that Lrrk2 deficiency attenuated lipopolysaccharide (LPS)-induced mRNA and/or protein expression of inducible nitric oxide synthase, TNF-α, IL-1β and IL-6. LPS-induced phosphorylation of p38 mitogen-activated protein kinase and stimulation of NF-κB-responsive luciferase reporter activity was also decreased in Lrrk2-KD cells. Interestingly, the decrease in NF-κB transcriptional activity measured by luciferase assays appeared to reflect increased binding of the inhibitory NF-κB homodimer, p50/p50, to DNA. In LPS-responsive HEK293T cells, overexpression of the human LRRK2 pathologic, kinase-active mutant G2019S increased basal and LPS-induced levels of phosphorylated p38 and JNK, whereas wild-type and other pathologic (R1441C and G2385R) or artificial kinase-dead (D1994A) LRRK2 mutants either enhanced or did not change basal and LPS-induced p38 and JNK phosphorylation levels. However, wild-type LRRK2 and all LRRK2 mutant variants equally enhanced NF-κB transcriptional activity. Taken together, these results suggest that LRRK2 is a positive regulator of inflammation in murine microglia, and LRRK2 mutations may alter the microenvironment of the brain to favor neuroinflammation.

Data from 82 purebred and crossbred Large White and Duroc barrows and gilts were used to describe the growth of carcass primal cuts, of tissues, and of several organs. Pigs were allowed ad libitum to a conventional diet, which contained com and soybean meal. Pigs were weighted weekly and were slaughtered when attained a liveweight over 90kg. An allometric pattern of growth was assumed. Within the observed range of liveweight, the carcass grew slower than the whole animal. An increase of carcass weight corresponds to a similar increase of lean, but also corresponds to a larger increase of fat tissues. A suggestion to slaughter pigs near to 90kg of liveweight is presented, in order to obtain leaner carcasses.

BACKGROUND: Brain inflammation is accompanied by brain injury. However, it is controversial whether inflammatory responses are harmful or beneficial to neurons. Because many studies have been performed using cultured microglia and neurons, it has not been possible to assess the influence of multiple cell types and diverse factors that dynamically and continuously change in vivo. Furthermore, behavior of microglia and other inflammatory cells could have been overlooked since most studies have focused on neuronal death. Therefore, it is essential to analyze the precise roles of microglia and brain inflammation in the injured brain, and determine their contribution to neuronal damage in vivo from the onset of injury. METHODS AND FINDINGS: Acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc) and the cortex of the rat brain. Inflammatory responses and their effects on neuronal damage were investigated by immunohistochemistry, electron microscopy, quantitative RT-PCR, and stereological counting, etc. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h. We defined as the core region the area where both TH(+) and Iba-1(+) cells acutely died, and as the penumbra the area surrounding the core where Iba-1(+) cells showed activated morphology. In the penumbra region, morphologically activated microglia arranged around the injury sites. Monocytes filled the damaged core after neurons and microglia died. Interestingly, neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (∼80% of that in the contralateral side) did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. CONCLUSIONS: Different cellular components (microglia, astrocytes, monocytes, and neutrophils) and different factors (proinflammatory and neurotrophic) could be produced in inflammatory processes depending on the nature of the injury. The results in this study suggest that the inflammatory responses of microglia and monocytes in response to ATP-induced acute injury could not be neurotoxic.

The paper describes the place and the role of civic education within the social system of the Republic of Macedonia. The main argument is that the implementation of the concept of civic education into the Macedonian educational system has successfully passed the initial and the subsequent introductory phase, and is nowadays facing the challenges of the mainstreaming phase. The situation at each stage is described in terms of the objectives, central issues, organization and teacher training.

O autor discute a necessidade de a escola resgatar, através da disciplina Arte-Educação, além das técnicas e práticas artísticas, o exercício da expressividade e da emoção da criança. Salienta a oportunidade de projetos que resgatem e dêem vida à experimentação nas quais a imaginação, a sensibilidade e a identidade aconteçam fora de programações competitivas e estereotipadas.

Abstract Background Heavy consumption of alcohol increases the risk of developing active tuberculosis (TB), contributes to delayed diagnosis and affects adherence to treatment. Within a large urban case-finding project, we aimed to determine the prevalence of and factors associated with alcohol use disorder (AUD) and to understand the challenges that people with AUD face while seeking for TB services and adhering to TB treatment. Methods We carried out an explanatory sequential study in two large urban districts in Uganda. We collected quantitative data on the prevalence of alcohol use disorder using the Cut, Annoyed, Guilty, Eye opener (CAGE) tool. We used a Poisson regression model with robust variance to examine factors associated with AUD. Both the crude and adjusted prevalence risk ratios with 95% confidence intervals were presented. We then conducted two focus group discussions with persons diagnosed with both TB and AUD. Focus group discussions (FGDs) were transcribed, data were analysed inductively and coded into themes using NVIVO version 12 software. Results Out of 325 people with TB people interviewed, 62 (18.7% 95% confidence interval [CI] 18–31%) screened positive for AUD. Majority 82.3% (51/62) were male. Being male aPR 2.32 (95% CI 1.19, 4.49) and living in an urban area aOR 1.79 (95% CI: 1.10, 2.92) were significantly associated with a positive screen. Among people who screened positive for AUD, there was a tendency towards suboptimal TB treatment outcomes, although this did not reach significance aPR 1.65 (95% CI: 0.95, 2.85). Fourteen people (eight male and six female) who screened positive for AUD attended two FGDs. These respondents often did not disclose alcohol use during TB treatment and missed clinic refill appointments due to lack of transport fares to the clinic. Conclusion A significant proportion of people with TB screened positive for AUD but did not disclose alcohol use to their healthcare workers. These patients experienced several challenges while on TB treatment. Therefore, TB care programs need to design interventions that actively assess for AUD and in order to address related challenges.

Abstract The aim of the present study was to elucidate the utility of Mesenchymal Stem Cell Antigen-1 (MSCA1) (tissue nonspecific alkaline phosphatase (TNAP)) as a potential marker for purification of human chondrocyte fraction with less heterogenous phenotype from those with osteogenic properties. Chondrocytes were isolated from human osteoarthritis cartilage and sorted according to MSCA1 expression by MACS (Magnetic-activated cell sorting) and FACS (Fluorescence-activated cell sorting) techniques (MSCA1high and MSCA1low), analyzed for gene expression, osteogenic and adipogenic differentiation capacities, and were compared between the sorted populations. Gene expression analyses revealed upregulation in osteogenic genes (ALPL and RUNX2) and significantly lower expression of chondrocyte-specific genes (COL2A1, SOX9 and MIA) in sorted MSCA1high, as compared to MSCA1low. Expression of Aldehyde dehydrogenase isoform gene ALDH1A2 was enriched in MSCA1low chondrocytes. Stronger osteogenic differentiation was observed in MSCA1high, as compared to the unsorted cells, and particularly, MSCA1low chondrocytes. Expression of MSCA1 in human chondrocytes is biased in their commitment to the osteogenic lineage. We demonstrate that MSCA1 can be used as a marker for separation of cells, prone to differentiate towards osteogenic lineage from those, retaining chondrogenic phenotype. This may allow enrichment of a chondrogenic population and separation from undesirable osteoprogenitors.

Abstract Active conservation of an ice sheet seeks to reduce ice sheet mass loss and sea level rise. Here we explore the response of Sermeq Kujalleq in Greenland to limiting warm water inflow to the fjord it terminates by raising the sill by an artificial barrier at its mouth. We asynchronously couple an ice sheet model with a fjord model, and simulate glacier evolution with varying climate scenarios from the year 2020 to 2100. The tallest barrier cools the fjord water and reduces melt at the ice front. But this has minor impacts on glacier retreat under SSP5-8.5 and SSP2-4.5. Cooling the atmospheric forcing to 1990s levels reduces glacier retreat, but even reducing water temperatures with a barrier cannot stabilize the glacier. The glacier seems to be in an unstoppable phase of marine ice sheet instability on a rapidly deepening retrograde sloping bed and in water much deeper than in 2000s.

Abstract Proteolytic processing of Receptor Tyrosine Kinases (RTKs) leads to the release of ectodomains in the extracellular space. These soluble ectodomains often retain the ligand binding activity and dampen canonical pathways by acting as decoy receptors. On the other hand, shedding the ectodomains may initiate new molecular events and diversification of signalling. Members of the TAM (TYRO3, AXL, MER) family of RTKs undergo proteolytic cleavage, and their soluble forms are present in the extracellular space and biological fluids. TAM receptors are expressed in professional phagocytes, mediating apoptotic cell clearance, and suppressing innate immunity. Enhanced shedding of TAM ectodomains is documented in autoimmune and some inflammatory conditions. Also, soluble TAM receptors are present at high levels in the biological fluids of cancer patients and are associated with poor survival. We outline the biology of TAM receptors and discuss how their proteolytic processing impacts autoimmunity and tumorigenesis. In autoimmune diseases, proteolysis of TAM receptors likely reflects reduced canonical signalling in professional phagocytes. In cancer, TAM receptors are expressed in the immune cells of the tumour microenvironment, where they control pathways facilitating immune evasion. In tumour cells, ectodomain shedding activates non-canonical TAM pathways, leading to epithelial-mesenchymal transition, metastasis, and drug resistance.

The study aims to examine the impact of international trade on the sustainability of regional ecosystems in Ukraine, particularly amid the ongoing Russia-Ukraine war. The paper applies econometric modeling, factor analysis, cluster analysis, and geographic information systems (GIS) for spatial analysis. Sustainability indicators include environmental resilience indicators (carbon emissions, water quality), economic stability metrics (GDP per capita, investment in green technologies), and social sustainability factors (employment rate, access to education and healthcare). Results indicate that a 1% increase in exports enhances sustainability indicators by 0.9%, while a 1% rise in imports or demographic density reduces these indices by 0.94% and 0.75%, respectively. Cluster analysis identifies five groups of regions with varying ecological resilience, revealing critical vulnerabilities in southern and eastern Ukraine where resilience indices are below 0.5. War actions exacerbate these issues, causing infrastructure destruction, soil and water degradation, and pollutant emissions ranging from 152.5 to 16,311.4 thousand tons. Recommendations include scaling up environmental protection investments by 20% (from the current 5,965–165,228 thousand UAH) and integrating sustainability standards into international trade policies to harmonize economic activities with environmental management in crisis and post-war recovery contexts.

Alpha‐smooth muscle actin (α‐SMA) expression in the stroma is linked to the presence of cancer‐associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor and α‐SMA‐expressing stromal cell compartments in pancreatic neuroendocrine tumors (PanNETs). The profiling was performed on tissues from eight retrospective cases (three grade 1, four grade 2, and one grade 3). Selected regions of interest were segmented geometrically based on tissue morphology and fluorescent signals from synaptophysin and α‐SMA markers. The α‐SMA‐expressing stromal‐cell‐associated genes were involved in pathways of extracellular matrix modification, whereas, in tumor cells, the gene expression profiles were associated with pathways involved in cell proliferation. The comparison of gene expression profiles across all three PanNET grades revealed that the differences between grades are not only present at the level of the tumor but also in the α‐SMA‐expressing stromal cells. Furthermore, the tumor cells from regions with a rich presence of adjacent α‐SMA‐expressing stromal cells revealed an upregulation of matrix metalloproteinase‐9 (MMP9) expression in grade 3 tumors. This study provides an in‐depth characterization of gene expression profiles in α‐SMA‐expressing stromal and tumor cells, and outlines potential crosstalk mechanisms.

Abstract Pathogenic variants in the creatine transporter gene SLC6A8, reported to represent 2% of all intellectual disabilities in males, result in a spectrum of behavioral abnormalities including developmental delay, intellectual disability, and deficit in speech. While at present there are no effective treatments available, preclinical development and testing of gene therapy and other approaches to increase brain creatine are being actively pursued. In studying a mouse model of the disorder, [18F]fluorodeoxyglucose ([18F]FDG)-based positron emission tomography (PET)/computed tomography (CT) was performed to assess brain glucose metabolism in wild type and creatine transporter mutant mice (Slc6a8 -/y ). The findings demonstrate marked differences in glucose metabolism in the brains of wild type and Slc6a8 -/y mice. In conducting behavioral phenotyping studies, notable abnormalities in behavior in the murine model led to additional studies in serotonin-mediated activity. Serotonergic signaling differences were detected between wild type and Slc6a8 -/y mice using 4-(2′-methoxyphenyl)-1-[2′-(N-2″-pyridinyl)-p-[18F]fluorobenzamido]ethylpiperazine ([18F]MPPF). These data demonstrate that [18F]FDG-PET and [18F]-MPPF-PET may serve as appropriate and sensitive biomarkers that could be used to assess the efficacy of not only new approaches in treating mutations of the creatine transporter SLC6A8 and their effectiveness in normalizing brain metabolism but also in enhancing our understanding of the mechanism of brain dysfunction that occurs in this complex brain disorder.

Abstract The molecular structure of an odor determines whether and how it is perceived by humans. However, the principles of how odorant chemistry links to perceptual patterns remain largely unknown and are primarily studied using odor rating datasets from highly trained olfactory experts, such as perfumers. This limits our knowledge of typical odor perception and its variability over individuals. We provide a dataset featuring free descriptions, evaluative ratings, and qualitative labels for 74 chemically diverse mono-molecular odorants, rated by a large sample of young adults. A total of 1,227 participants described and rated the odors, and completed questionnaires covering their demographic background, personality traits, and the role of olfaction in their daily lives. The dataset offers a valuable foundation for research aimed at understanding the fundamentals of olfactory perception.