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Synthesis of New Biological Active Compounds from Linoleic Acid of Melon Seed and Pro...
Hanaa Soliman

Hanaa Soliman

July 16, 2020
Melon seed was dried, oil was extracted, its parameters had been determined. The produced oil was then hydrolyzed into glycerol and mixture of free fatty acids. Fatty acids mixture was separated. Then, by means of supercritical CO2 extractor linoleic acid was extracted individually. linoleic acid was then confirmed according to its melting point, GC-MS after esterfication , elemental analysis, H1NMR and mass spectrometry (ms) of the corresponding methyl ester in order to detect the corresponding molecular ion peak. The pure individual linoleic acid went through several chemical reactions into derivatives of deferent heterocyclic compounds. The structure elucidation of all synthesized compounds was established according to elemental analysis and spectral data (IR, 1H NMR, 13C NMR and MS). Then the prepared compounds were tasted for their antimicrobial activities. While, the leftover melon seed cake was used for ash production, thus, it was carbonized, and its elemental content was detected, then it was used as a natural adsorbent for improving the quality of used fried oil. Where a frying process was achieved for 24 h.. Some of the used oil was treated with ash of melon seed cake at 105 ̵̊C for 15 min. and compared to other portion that was treated with Magnesol XL at the same conditions. All Physical and chemical parameters of fresh oil, used oil, used oil treated with ash of melon seed cake and used oil treated with Magnesol XL were determined individually.
Mancais de deslizamento: seleção correta para um projeto de máquina confiável
David Lira Nunez

David Lira Nunez

March 29, 2021
IntroduçãoPara \citet*{Norton_2011}, mancais são por definição constituídos de duas partes em contato com movimento relativo entre si. O mancal em termos gerais, existe sempre que há duas partes móveis, onde uma delas , normalmente um eixo, se esfrega com uma camisa ao redor dela, chamado de bucha.  Esses eixos normalmente  são de aço, ferro fundido ou algum outro material estrutural, já as buchas normalmente são encontradas de bronze, babbitt, polímeros ou algum compósito.  As buchas permitem o deslizamento confiável do eixo, seja radial ou axial e elas têm o formato cilíndrico,  seja bipartido ou não.No trabalho de  \citet*{Nu_ez_2018}, busca-se a implementação de um método que gerencie a sáude das máquinas, por meio do monitoramento dos seus elementos mecânicos, em pleno funcionamento, para garantir a vida útil projetada para a máquina como um todo. Nesse trabalho é usada a norma IEC 60050, que define confiabilidade como a capacidade de um elemento mecânico executar uma função conforme o necessário, sem falha, por um determinado intervalo de tempo e sob determinadas condições de operação. Nesse contexto, a confiabilidade de uma bucha pode ser comprometida por não entregar o tempo de funcionamento desejado, pela presença de uma falha ou avaria, dependendo de aspectos como: modo de operação, projeto da máquina para seleção de seus elementos mecânicos, condições ambientais, má lubrificação e falta de manutenção. Normalmente, precisa-se de lubrificação em qualquer mancal para reduzir o atrito e remover o calor. Os mancais podem rolar, escorregar ou fazer ambos simultaneamente. Os mancais são necessários nos mais diversos tipos de máquinas rotativas, como motores, bombas, compressores, turbinas, entre outros. Sem os mancais não seria possível a transmissão ideal do movimento e potência \citep*{Castro_2007}.
Novel therapies in β- thalassemia
Laura Grech
Karen Borg

Laura Grech

and 2 more

July 16, 2020
Beta-thalassaemia is one of the most significant haemoglobinopathies worldwide resulting in the synthesis of little or no β-globin chains. Without treatment, β-thalassaemia major is lethal within the first decade of life due to the complex pathophysiology which leads to wide clinical manifestations. Current clinical management for these patients solely relies on repeated transfusions followed by iron chelating therapy which can eventually results into multi-organ damage. A number of novel approaches to correct the resulting α/β globin chain imbalance are currently being developed. These include reactivation of foetal haemoglobin by pharmacological compounds, allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy. Up to now, the only curative treatment for beta-thalassemia is HSCT, but this is a risky and costly procedure. Gene therapy either by gene addition or gene editing is emerging as a powerful approach to treat this disease. Gene addition is currently based on transplantation of autologous hematopoietic stem cells genetically modified with an integrating lentiviral vector expression the globin gene while gene editing involves the use of CRISPR/Cas9 to correct the causative mutation. Although the early outcomes of the clinical trials in gene therapy are showing promising results, they have also highlighted a number of limitations. In this review we will discuss about the current management strategies used to treat beta-thalassaemia and also focus on novel therapies.
Microbial fatty acid transport proteins and their biotechnological potential
José Manuel Salvador López
Inge Van Bogaert

José Manuel Salvador López

and 1 more

July 16, 2020
Fatty acid metabolism has been widely studied in various organisms. However, fatty acid transport has received less attention even though it plays vital roles for the cells, such as export of toxic free fatty acids or uptake of exogenous fatty acids. Hence, there are important knowledge gaps in how fatty acids cross biological membranes and many mechanisms and proteins involved in these processes still need to be determined. The lack of information is more predominant in microorganisms, even though the identification of fatty acids transporters in these cells could lead to new drug targets or improvements in microbial cell factories. This review provides a thorough analysis of the current information on fatty acid transporters in microorganisms, including bacteria, yeasts and microalgae species. Most information available relates to the model organisms Escherichia coli and Saccharomyces cerevisiae, but transport systems of other species are also discussed. Intracellular trafficking of fatty acids and their transport through organelle membranes in eukaryotic organisms is described as well. Finally, applied studies and engineering efforts using fatty acids transporters are presented to show the applied potential of these transporters and to stress the need for further identification of new transporters and their engineering.
Prereview for"Parasitologia desenhada: uma ferramenta auxiliar no aprendizado de disc...
Andreia Weiss

Andreia Weiss

July 20, 2020
Resumo:  Este é um Grupo de Revisores de pré-impressão da Revista Ensino & Pesquisa. O texto avaliado foi "Parasitologia desenhada: uma ferramenta auxiliar no aprendizado de discentes do curso de medicina veterinária", de  Isabella Vilhena Freire Martins, Jankerle Neves Boeloni,Josileia curty de oliveira, cíntia das Chagas Bernardo ( DOI: 10.22541/au.159406482.27359109)  O artigo das autoras Isabella Vilhena Freire Martins, Jankerle Neves Boeloni, Josileia Curty de Oliveira e Cíntia das Chagas Bernardo, apresenta a proposta de metodologia – jogo didático desenvolvido na disciplina de Parasitologia Veterinária, ofertada no 3º período do Curso de Medicina Veterinária da UFES – Campus de Alegre. A revisão bibliográfica está constituída em diferentes autores e comentadores sobre a utilização de jogos e sua possibilidade de ser utilizada e ampliada para o ensino superior. No decorrer da revisão bibliográfica algumas questões são destacadas pelas autoras como a perspectiva de utilizar ferramentas e/ou metodologias diferenciadas que diferem do processo tradicional do ensino – aprendizagem, que seria as metodologias ativas (BORGES; ALENCAR, 2014; ROSA, 2017; MACEDO et al., 2018). E, no caso, definem o jogo como uma possibilidade nesse processo, evidenciando a ludicidade como ponto para o interesse por parte do aluno pelo conteúdo que está sendo ministrado, buscando autores que desenvolveram pesquisas nesse sentido na Medicina Veterinária (ALMEIDA et al., 2012; BRAGAGNOLLO et al., 2019; PIZUTTI et al., 2018). No decorrer da mesma, apresentam os autores Melo, Avila e Santos (2017) e Covos et al. (2018)  para compreender a relação entre o jogo lúdico e o processo de ensino – aprendizagem.Para tanto, esclarecem que a pesquisa se configurou como qualitativa e o jogo didático intitulado “Parasitologia Desenhada”, inspirada num jogo comercial (Imagem & Ação®), se baseou em um dos conteúdos que compreende a Disciplina Parasitologia Veterinária que são as características morfológicas dos parasitos. O referido jogo foi aplicado durante nove (9) anos para nove (9) turmas de alunos do 3º período do referido curso, totalizando 441 alunos participantes. O jogo prevê a interação entre o grupo para chegar ao fim proposto e, todos os membros do grupo tem sua vez de ser o responsável pelo registro da imagem para que seu grupo possa identificar o parasita a que se refere.As autoras analisam que esse jogo possibilita a interação entre docente e discentes, evidenciando o processo de motivação e compreensão do que foi pontuado no jogo com o conteúdo ministrado na disciplina. Por fim concluem que a utilização do jogo é possível, estimulador e se configura em um caminho para se trabalhar no Ensino Superior. Ponderações quanto ao artigo:O artigo possui relevância e possibilita o olhar para o processo de ensino – aprendizagem pelo método de trabalho em grupo - jogo. Algo valido e necessário de ser discutido e disponibilizado.Todavia, após a análise do mesmo, sugiro que alguns pontos necessitam ser revistos pelas autoras:1) revisão bibliográfica: o artigo apresenta alguns autores e comentadores que são utilizados para referendar o uso dos jogos didáticos e sua relação com o processo de ensino-aprendizagem, no entanto, o mesmo não possui um teórico que de corpus ao processo de ensino e aprendizagem e/ou das metodologias ativas. Dessa forma, é importante que as autoras vislumbrem esse teórico que fundamenta esses dois elementos oque, por sua vez, irá  auxiliar no item “resultados e discussão”;2) os jogos e/ou atividades que estimulam o lado lúdico do conteúdo é utilizado com mais frequência em outros cursos/áreas do conhecimento, no entanto, estes estão sendo visualizado como uma possibilidade na Medicina Veterinária (explicar e explorar essa possibilidade, tendo em vista que é o curso foco do artigo). Isso é necessário até para compreender que  somente a fixação não dá conta do processo de aprendizagem (o que é defendido pelas autoras quanto estas esclarecem que as metodologias tradicionais deixam a desejar no processo de ensino-aprendizagem);3) resultados e discussão: a realização da estratégia possui pontos interessantes e permite vislumbrar outra possibilidade de estratégia de ensino para o ensino, no entanto, seria importante   a) analisar o processo da aplicação do jogo com os autores e o teórico que fundamenta o processo de ensino-aprendizagem e a metodologia ativa. Assim, o leitor compreenderá quais foram os desafios e as descobertas com essa ferramenta. Cuidar para não trazerem elementos que no decorrer da discussão ficam sem serem explicadas ou relacionadas com o objeto do artigo; b) apresentar e analisar como foi o processo da avaliação que o docente realizou no decorrer da aplicação da ferramenta, pois no 5º parágrafo da página n. 8 começa a ser mencionado que “[...] foi possível avaliar a aprendizagem e a memorização [...]”.4) Por fim, sugiro rever a relação e/ou o encadeamento das ideias entre as frases e os parágrafos, pois em alguns momentos, as ideias estão “cortadas” / fragmentadas sem a articulação e coerência necessária.
Insight Into The X-Ray Absorption Spectra of Cu-Porphyrazines From Electronic Structu...
Esma  Boydas
Bernd Winter

Esma Boydas

and 3 more

July 16, 2020
Transition metal porphyrazines are a widely used class of compounds with applications in catalysis, organic solar cells, photodynamic therapy and nonlinear optics. The most prominent members of that family of compounds are metallophtalocyanines that have been subject of numerous spectroscopic and theoretical studies. In this work, the electronic structure and X-ray absorption characteristics of three Cu-porphyrazine derivatives are investigated by means of modern electronic structure theory. More precisely, the experimentally observed N K-edge and Cu L-edge features are presented and reproduced by time-dependent density functional theory, restricted open-shell configuration interaction and a restricted active space approach. Where possible, the calculations are used to interpret the observed spectroscopic features in terms of electronic transitions and furthermore connect spectral differences to chemical variations. Part of the discussion of the computational results concerns the impact of various parameters and approximations that enter the calculations, e.g. the choice of active space.
Pigs are not susceptible to SARS-CoV-2 infection but are a model for viral immunogeni...
Júlia Vergara-Alert
Jordi Rodon

Júlia Vergara-Alert

and 13 more

July 16, 2020
Conventional piglets were inoculated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through different routes, including intranasal, endotracheal, intramuscular and intravenous ones. Although piglets were not susceptible to SARS-CoV-2 and lacked lesions or viral RNA in tissues/swabs, seroconversion was observed in pigs inoculated parenterally (intramuscularly or intravenously).
New aspects of stomatal opening mechanism
Joon Sang Lee

Joon Sang Lee

July 16, 2020
In the mechanisms of stomatal opening, the transports of osmotic materials between the guard cell cytoplasm and vacuole have not been studied much. There were also important lacks of understanding about tonoplast transport proteins and channels. Tonoplast has been found to have many types of channels related to K+ transport, among which are inward-K+ channels/FV, outward-K+ channels/FV, outward-TPK/VK channels and TPC1/SV channels. The two H+ transport enzymes in tonoplast, H+-ATPase and H+-PPase, transport H+ from the cytoplasm to vacuole very actively. They serve to create an ideal pH condition between vacuole and cytoplasm to facilitate the many metabolisms in the cell. The cytosolic K+ cannot easily enter the vacuole to fill the charge balances, because vacuole is too full of positive charges. Therefore, in order to increase the osmotic pressure of the guard cell vacuole, it is necessary to transport solute that can replace K+. Tonoplast contains sucrose-H+ antiports, an active transport protein that can transport cytoplasmic sucrose to vacuole. Although various solutes including K+ are required for stomata to open, sucrose is believed to be the most important substance that can increase the vacuole’s osmotic pressure.
Emerging approaches for the treatment of Alzheimer disease: Targeting NF-κB pathway
Akansh Goel
Shamsher Singh

Akansh Goel

and 1 more

July 16, 2020
Alzheimer’s disease (AD) is the most predominant neurodegenerative disorder and form of dementia around the globe. Despite its prevalence, only a few drugs approved for AD and all concerned with the symptoms rather than the underlying cause of the disorder. Classic neuropathological disease hallmarks (β-amyloid & NFT) and sporadic AD risk genes APOE that activate NF-κB, yet may incite pathology. NF-κB inhibition is a current strategy to counter neuroinflammation and neurodegeneration in the brain of individuals with AD, and numbers of NF-κB modulators are being examined in clinical trials. Modification of the NF-κB system focuses mainly on preventing oxidative stress with the pathway to cell death and managing the levels of neurotransmitters. This review summarizes several shreds of evidence indicating the upregulation of NF-κB in AD and illustrates its function in current efforts for a therapeutic approach. The goal of innovative research strategies is to modulate NF-κB, providing an alternate treatment that may help individuals with AD and generate hope for potential clinical advancements in AD.
CKIP-1 participates in the activation of Nrf2 signaling pathway by Cx43 and the regul...
Heqing Huang
Yan Yang

Heqing Huang

and 5 more

July 16, 2020
Abstract Background and Purpose We previously reported that both Cx43 and CKIP-1 attenuated diabetic renal fibrosis via the activation of Nrf2 signaling pathway. However, whether CKIP-1, a scaffold protein, participates in regulating the activation of Nrf2 signaling pathway by Cx43 remains to be elucidated. Experimental Approach The effect of adenovirus-mediated Cx43 overexpression on renal fibrosis in CKIP-1−/− diabetic mice was investigated. Cx43 overexpressed plasmid and CKIP-1 small interfering RNA were simultaneously transfected into GMCs and the activity of Nrf2 signaling pathway was observed. The interaction between Cx43 and CKIP-1 was analyzed by immunofluorescence and immunoprecipitation assays. Key Results Overexpression of Cx43 could significantly alleviate renal fibrosis by activating the Nrf2 pathway in diabetic mice, but have no obvious effect in CKIP-1−/− diabetic mice. The effect of activation of Nrf2 signaling pathway by Cx43 was blocked by CKIP-1 depletion. Cx43 interacted with CKIP-1, and the interaction was weakened by high glucose treatment. Cx43 regulated the expression of CKIP-1 and the interaction of CKIP-1 with Nrf2 via Cx43 carboxyl terminus (CT) domain, thereby activating Nrf2 signaling pathway. Conclusion and Implications CKIP-1 participates in regulating the activation of Nrf2 signaling pathway by Cx43, the mechanism of which might be related to the interaction of CKIP-1 with Nrf2 through Cx43 CT. Our study provides further experimental basis for targeting the Cx43-CKIP-1-Nrf2 axis to resist diabetic renal fibrosis.
Hypothesis Article: Free SARS-CoV-2 spike protein S1 particles may act as a factor of...
Andrey Letarov
Vladislav Babenko

Andrey Letarov

and 2 more

July 16, 2020
The disbalance of the renin-angiotensin system was suggested to play an important role in the pathogenesis of the COVID-19 disease. Previously it has been shown that ACE2 expression in downregulated in the murine model in response to SARS-CoV infection and may be also induced by the recombinant spike protein alone. We hypothesize that the soluble SARS-CoV-2 spike protein S1 subunits shed from the infected cells and from the virions in vivo may bind to the ACE2 receptor and trigger ACE2 downregulation. Decreased ACE2 activity on the background of the constant or increased ACE activity in the lungs may lead to the prevalence of angiotensin II effects over angiotensin(1-7) connected to increased thrombosis, inflammation and pulmonary damage.
Investigating the potential of clinical and biochemical markers to diagnose functiona...
Sara Abou Sherif
Rebecca Newman

Sara Abou Sherif

and 8 more

July 16, 2020
Objective: Functional hypothalamic amenorrhoea (FHA) is a common cause of amenorrhoea, but few non-specialist clinicians are able to diagnose affected women. The aim of this study was to investigate the clinical and biochemical features of FHA, compared to that of polycystic ovarian syndrome (PCOS) and assess the diagnostic performance of the different parameters for differentiating between the two conditions. Design: A retrospective observational study Setting: Specialist reproductive endocrine gynaecology clinic, St Mary’s Hospital, London, UK Population: Women diagnosed with FHA and PCOS following specialist assessment. Methods: Clinical and biochemical data were collected from electronic hospital data base. Results: Compared with PCOS, women with FHA had significantly lower body mass index (BMI) (20.1±2.9 vs 31.1±7.8 kg/m2, P<0.0001) and a thinner endometrium (3.75±2.23 vs 6.82±3.32 mm, P<0.0001). Women with FHA had significantly lower luteinising hormone (LH) (3.46±7.31 vs 8.79±4.98 IU/L, P< 0.0001), as well as lower LH: follicle stimulating hormone (FSH) ratio, estradiol, thyroid-stimulating, free thyroxine and prolactin levels; there was no significant difference in FSH levels. Low BMI had the greatest predictive performance for FHA (area under the curve [AUC]; 0.93, P<0.001), followed by low estradiol (AUC 0.89, P<0.001), low LH (AUC 0.88, P<0.001) and LH:FSH ratio (AUC 0.86, P<0.001). Conclusions: Our data provides quantification for diagnostic accuracy of clinical parameters to differentiate FHA from PCOS, namely low BMI, estradiol, LH and LH:FSH ratio. These data could help clinicians more reliably diagnose FHA in women with secondary amenorrhoea. Key words: Amenorrhoea, Hypogonadism, Polycystic Ovarian Syndrome, Luteinising Hormone
Direct and indirect effects of rainfall and vegetation coverage on runoff, soil loss,...
Jiayi Huo
Changjun Liu

Jiayi Huo

and 6 more

July 16, 2020
High nitrogen (N) and phosphorus (P) levels are the main causes of eutrophication of water bodies, and the chemical oxygen demand (COD) is one of the indices of relative organic matter content. Several simulated rainfall experiments have been conducted to investigate the effects of a single controlling factor on soil and nutrient loss. However, the role of precipitation and vegetation coverage in quantifying soil and nutrient loss is still unclear. We monitored runoff, soil loss, and soil nutrient loss under natural rainfall conditions from 2004 to 2015 in runoff plots around Beijing. Soil erosion was significantly reduced when vegetation coverage reached 20 and 60%. At levels below 30%, nutrient loss did not differ among different vegetation cover levels. Minimum soil N and P losses were observed at cover levels above 60%. Irrespective of the management measure, soil nutrient losses were higher at high-intensity rainfall events compared to low-intensity events (p < 0.05). We applied structural equation modelling (SEM) to systematically analyze the relative effects of rainfall characteristics and environmental factors on runoff, soil loss, and soil nutrient loss. At high-intensity rainfall events, neither vegetation cover nor antecedent soil moisture content (ASMC) affected runoff and soil loss. After log-transformation, soil nutrient loss was significantly linearly correlated with runoff and soil loss (p < 0.01). In addition, we identified the direct and indirect relationships among the influencing factors of soil nutrient loss on runoff plots and constructed a structural diagram of these relationships. The factors positively impacting soil nutrient loss were runoff (44-48%), maximum rainfall intensity over a 30-min period (18-29%), rainfall depth (20-27%), and soil loss (10-14%). Studying the effects of rainfall and vegetation coverage factors on runoff, soil loss, and nutrient loss can improve our understanding of the underlying mechanism of slope non-point source pollution.
Preparedness for Caesarean section in COVID-19 positive pregnant patient.
Jasiya MH
ASHOK  DEVOOR

Jasiya MH

and 2 more

July 16, 2020
Introduction : COVID-19 in pregnancy,the outcome is not very clearly defined, this study guides for step wise approach for preparedness if an C-section is planned for COVID-19 positive pregnant patient Aims and objective: • Step wise guide to prepare for C- section for COVID-19 positive pregnant patient Methods : This step wise guide has been formulated after referring guidelines from RCOG,ACOG,FOGSI, and also the SOP followed in our bowring and lady Curzon hospital. Conclusion: Step wise approach allows the surgeon and other health care workers to be adequately prepared both mentally and physically and better and efficient patient care
Dexamethasone, pro-resolving lipids and resolution of inflammation in COVID-19
Evangelos Andreakos
Maria Papadaki

Evangelos Andreakos

and 2 more

July 16, 2020
EDITORIAL Coronavirus disease‐19 (COVID‐19) is a new disease caused by SARS‐CoV2. Since the beginning of 2020, it has become one of the main challenges of our times, causing a high incidence of severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure and death1. At the root of COVID-19 lies the sudden development of ‘cytokine storms’, hyper-inflammatory responses involving the release of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-1, IL-8, and MCP-1) that impair the gas exchange function of the lung and lead in select patients, mostly with underlying comorbidities, to multiorgan failure and death1,2. Additional complications triggered by ‘cytokine storms’ include endothelial dysfunction and hypercoagulation, increasing the risk of thromboembolytic events, and life-threatening cardiovascular complications. Anti-inflammatory therapies are thus being considered for alleviating the damaging side effects of hyper-inflammation with many trials including anti-cytokine biologicals, disease-modifying antirheumatic drugs (DMARDs) and corticosteroids being ongoing3. Surprisingly, among them dexamethasone has taken center stage as initial results from the RECOVERY trial, a large multicenter randomized open-label trial for hospitalized patients run in the United Kingdom, revealed notable efficacy in the treatment of critically ill COVID-19 patients4.Dexamethasone is one of the oldest synthetic glucocorticoid agonists synthesized in 1957 and introduced into the clinic in 1961. When administered at 6 mg daily, either orally or intravenously for 10 days, dexamethasone was shown in the RECOVERY trial to improve survival rates of hospitalized patients with severe COVID-19 receiving oxygen or being on mechanical ventilation by a remarkable 30%4. Benefit was restricted to patients requiring respiratory support whereas in milder cases this was not clear. This notable efficacy of dexamethasone treatment goes against the current view of corticosteroid use in respiratory viral infections which remains contradictory. Although corticosteroids improve ventilator weaning and can lower the intensity of the host response to the virus, tempering the ‘cytokine storm’ and limiting immunopathology, they can also reduce viral clearance and lead to more severe disease. Understanding therefore how dexamethasome mediates its effects is of paramount importance.Dexamethasone, as other corticosteroids, is held to mediate its anti-inflammatory and immunosuppressive effects via the glucocorticoid receptor. Upon ligand binding, the receptor-corticosteroid molecule complex moves into the cell nucleus, where it dimerizes and binds to glucocorticoid response elements (GRE), acting as transcriptional repressor or transactivator of diverse sets of genes. This results in the inhibition of inflammatory cell activity, including neutrophils, macrophages and lymphocytes, and the suppression of pro-inflammatory cytokines such as TNF and interleukins and other genes such as cyclooxygenase-2 and inducible nitric oxide synthase5. However, we have recently uncovered that dexamethasone can also induce the D-series proresolving lipid mediator pathway leading to the production of 17-HDHA and the protectins D1 and DX6. These are potent major players of the molecular machinery driving the resolution of inflammation, i.e. the proper regulated termination of pro-inflammatory responses involving the catabolism of pro-inflammatory mediators, the removal of inflammatory cells and the restoration of the tissue in a timely and highly coordinated manner7. Although resolution of inflammation has long been considered to occur spontaneously as a result of the waning of pro-inflammatory responses, this is now known to be an ordered and highly regulated process involving the timely production of enzymatically oxygenated lipid-derived mediators such as protectins, D-series resolvins and maresins derived from the omega-3 fatty acid docosahexaenoic acid (DHA), E-series resolvins derived from eicosapentaenoic acid (EPA), and lipoxins biosynthesized from omega-6 fatty acids following eicosanoid class switching7. Interestingly, certain lipid mediators have been shown to exert additional non-conventional functions; resolvin D4 can attenuate pathologic thrombosis, reduce NETosis and promote clot removal8 which is now recognized as a key pathology of COVID-19 infection, while resolvin E4 (RvE4) stimulates efferocytosis of senescent erythrocytes in hemorrhagic exudates especially under hypoxic conditions that characterize COVID-199. Moreover, corticosteroids have been reported to reduce fibrinogen and procoagulant factors under pro-inflammatory conditions and increase anticoagulant factors10.The ability of viral infections to induce proresolving lipids has been reported earlier. Toll-like receptor 7 (TLR7), a major pattern recognition receptor of viral RNA, activates PD1 and PDX production11. Moreover, influenza virus infection has been demonstrated to drive proresolving lipid mediator networks including the production of PD1 which limits influenza pathogenicity by directly interacting with the RNA replication machinery to inhibit viral RNA nuclear export12,13. Notably, in particularly virulent strains of influenza virus such as the H5N1 avian strain, PD1 formation is not sufficiently upregulated, leading to more efficient viral replication and host demise12. It is therefore plausible that the efficacy of dexamethasone in COVID-19 is due at least in part to its ability to induce proresolving lipid mediators that possess multiple anti-inflammatory and proresolving actions tempering down inflammation and promoting its resolution, preventing coagulation and enhancing viral and bacterial clearance (Figure 1) yet are not immunosuppressive . Whether other corticosteroids beyond dexamethasone can also mediate such effects, and to what extent, is not known. Whether inhalable corticosteroids, such as those given to asthmatic patients, can also induce proresolving lipid mediator networks locally and thus prevent the development of severe SARS‐CoV‐2 infection remains to be determined. There is evidence that asthmatic patients exhibit reduced incidence of severe and/or critical COVID-1914.Recently, COVID-19 patients showed increased association of serum arachidonate-derived proinflammatory lipid mediators, e.g. prostaglandins, in severe COVID -19 infections while some pro-resolving mediators such as resolvin E3 were up-regulated in the moderate COVID-19 group suggesting that an imbalance in lipid mediators with a swift toward pro-inflammatory mediators in severe disease may contribute to COVID-19 disease severity15. Although the involvement of proresolving lipid mediator pathways in COVID-19 is an attractive hypothesis, further evidence from human trials is needed as there are no studies at present reporting the induction or modulation of such networks in the context of the various disease stages and treatments. It is thus of uttermost priority to investigate proresolving lipid mediators in COVID-19, in a temporal and longitudinal manner, as modulating these networks either through drug treatment or direct administration of resolvin and protectins agonists has the potential to affect this highly lethal and devastating disease in a way other approaches cannot. Such studies are therefore eagerly awaited.
Maternal pre-pregnancy body mass index, gestational weight gain, and risk of childhoo...
Rong Wu
Runhui Gu

Rong Wu

and 5 more

July 16, 2020
Introduction: The goal of this study was to evaluate the association between maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and risk of childhood asthma/wheeze by conducting a meta-analysis of cohort studies. Methods: A systematic literature search of several databases was conducted through January 2020 to identify relevant studies. The exposure of interest was maternal pre-pregnancy BMI (e.g., underweight, overweight, obesity, and continuous BMI) and GWG (e.g., inadequate GWG, excessive GWG, GWG < 9 kg, GWG > 15 kg, and continuous GWG). Random-effects models were used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Twenty-one cohort studies were included (N = 150,198 mother-child pairs). Age of children was 3 months to 16 years. Maternal overweight (OR = 1.13; 95% CI: 1.07 - 1.19) and obesity (OR = 1.39; 95% CI: 1.23 - 1.58) were associated with higher odds of childhood asthma/wheeze; each 1-kg/m2 increase in maternal pre-pregnancy BMI was associated with a 4% increase in the odds of childhood asthma/wheeze. GWG < 9 kg (OR = 1.08; 95% CI, 1.01 - 1.14) was slightly associated with higher odds of childhood asthma/wheeze. Subgroup analyses have identified several variables associated with the between-study heterogeneity. Conclusions: Maternal overweight and obesity are associated with an elevated risk of childhood asthma/wheeze, suggesting that maternal pre-pregnancy BMI need to be considered in studies on the early origins of asthma. Further studies are needed to confirm the association between GWG and risk of childhood asthma/wheeze.
Association of the maternal gut microbiota/metabolome with cord blood CCL17
Hiromi Tanabe
Kenichi SAKURAI

Hiromi Tanabe

and 14 more

July 16, 2020
BACKGROUND: Chemokine (C-C motif) ligand 17 (CCL17; also known as thymus and activation-regulated chemokine or TARC) is a pro-allergic factor, and high CCL17 levels in cord blood (CB) precede the allergic predisposition later in life. Offspring of pregnant mice treated with short-chain fatty acid (SCFA) have been shown to be protected against allergic diseases. The maternal microbial metabolome during pregnancy may affect foetal allergic immune responses. To examine this, the associations between CB CCL17 and gut SCFA levels in pregnant Japanese women were investigated here. METHODS: This study was conducted as part of the Chiba Study of Mother and Child Health; 434 healthy pregnant women were recruited. The CB CCL17 and maternal non-specific IgE levels were measured using CB sera at birth and maternal sera at 32 weeks of gestation. Stool samples were collected from pregnant women at 12 (n = 59) and 32 (n = 58) weeks of gestation and used for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. RESULTS: The CB CCL17 levels correlated negatively with butyrate concentrations at 12 weeks of gestation. In contrast, CB CCL17 levels correlated positively with isobutyrate levels at 12 weeks of gestation, and valerate and lactate concentrations at 32 weeks of gestation in maternal faeces. CONCLUSION: The metabolites in maternal faeces may alter the foetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring, even before birth.
Poor diet quality in childhood cancer patients during treatment: A target for nutriti...
Jennifer Cohen
Emma Goddard

Jennifer Cohen

and 4 more

July 16, 2020
Background With improved survivorship and long-term health outcomes, the long-term nutritional management of childhood cancer survivors, from diagnosis to long-term follow-up, has become a priority. The aim of this study was to assess diet quality of children receiving treatment for cancer. Procedure Participants were parents of childhood cancer patients who were receiving active treatment and not receiving supplementary nutrition. A three-pass 24-hour dietary recall assessed food and nutrient intake. Serves of food group intakes and classification of core and discretionary items were made according to the Australian Dietary Guidelines and compared with age and sex recommendations. Results Sixty-four parents participated (75% female). Nearly all children were not consuming adequate intake of vegetables (94% of patients), fruit (77%) and milk/alternatives (75%). Of the vegetables that were consumed, half were classified as discretionary foods (e.g. chips/fries). Nearly half (49%) of children exceeded recommendations for total sugar intake and 65% of patients had an excessive sodium intake. Discussion The diet quality of children undergoing treatment for cancer is generally poor. Information provided during treatment should focus on educating parents on a healthy diet for their child, the importance of establishing healthy eating habits for life, and strategies to overcome barriers to intake during treatment.
Experiences in academic publication among ENT trainees in the UK: results from a nati...
Shayan Shahidi
Max Osborne

Shayan Shahidi

and 4 more

July 16, 2020
Objective: To determine the number of academic papers which have been submitted and published by ENT specialty trainees at each level of higher surgical training. Design: A cross-sectional survey was designed and validated according to the ‘Good Practice in Conduct of and Reporting of Survey Research’ checklist. Settings: Voluntary completion of a web-based questionnaire which was distributed to participants between 11 May – 22 June 2020. Participants: All ENT higher surgical trainees (ST3-ST8 level) in the UK. Main outcomes measured: The number of submitted and published articles by each higher surgical trainee. Comparisons were made between deaneries, training grades and trainees who had achieved a higher degree. Trainees in academic training pathways and those in less than full-time training were analysed separately. Results: One hundred fifty-three ENT speciality trainees across the UK took part in the survey, giving a national response rate of 46.5%. There was a slight male preponderance in the respondents, with 85 males and 68 females completing the survey. Across all years of training, the mean number of first author publications was three and for non-first author publications the mean number was two. For trainees at ST8 level, these numbers were nine and five, respectively. Trainees undertaking a PhD programme produced a mean number of nine first author publications – 5.31 more than the rest (p < 0.0001). Those in academic training pathways achieved 3.48 more publications compared to those who were not (p = 0.092). Trainees with additional undergraduate degrees and those in less than full-time training had an overall lower number of first author publications compared to the general cohort. Conclusions: ENT specialty trainees achieve a higher average number of academic publications than is currently required in order to successfully obtain a Certificate of Completion of Training (CCT). This is particularly the case for trainees in an academic training programme and those with a higher degree. It is the authors’ hope that the data from this study will help in informing and guiding junior trainees, educational supervisors and training programme directors when considering the level of research engagement required for gaining a CCT.
Prognostic sensibility of clinical scales in Bell’s Palsy: a prospective longitudinal...
Diane Picard
Rémi Hervochon

Diane Picard

and 5 more

July 16, 2020
Introduction: The first aim of the study was to compare three clinical scales at baseline: the Sunnybrook Facial Grading System (SFGS), the eFACE and the MBLF protocol. Then we intend to specify their sensibility to predict sequelae of Bell’s palsy at 12 months. Methods: We carried out a longitudinal study of 23 patients with Bell’s palsy. We reported every three months, from baseline to follow-up at 12 months, all the results of their facial assessment. In order to precise the criterion validity of the three clinical scales at baseline, effect of House and Brackmann severity grades was tested on SFGS composite score, eFACE dynamic score and MBLF total score. Then, these three scores were compared between group A (patients without sequelae at 12 months) and group B (patients with sequelae). Sensibility in predicting sequelae at 12 months was specified with Receiver Operating Characteristics curve for each clinical scale. Results: Grades effect on each clinical scale was found (p< .005). At baseline, no significant difference was observed between group A and group B on clinical scales. At three months, only the MBLF total score was significant to predict recovery (χ2 = 8.37, p < .0038*, AUC = .769). From the 6th month, the three clinical scales could predict sequelae at 12 month (p <.005). Conclusion: Clinical tools are essential to assess patients with Bell’s palsy at baseline and follow-up. At baseline, the dynamic scores are not significantly different. At 3 months, only the MBLF significantly discriminated patients with or without sequelae at 12 months. At 6 months, all three scales were able to predict sequelae at 12 months.
Sulforaphane: from death rate heterogeneity in countries to candidate for prevention...
Jean Bousquet
Josep Anto

Jean Bousquet

and 8 more

July 16, 2020
To the Editor, Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane] is a clinically relevant nutraceutical compound present in cruciferous vegetables (Brassicaceae). It is used for the prevention and treatment of chronic diseases and may be involved in ageing.1Along with other natural nutrients, sulforaphane has been suggested to have a therapeutic value for the treatment of the coronavirus disease 2019 (COVID-19).2 Sulforaphane is an isothiocyanate stored in its inactive form glucoraphanin.3 The enzyme myrosinase, found in plant tissue and in the gut microbiome, is involved in the conversion of glucoraphanin to its active form sulforaphane.4
The influence of food histamine intake on asthma activity
Emilia Vassilopoulou
George Konstantinou

Emilia Vassilopoulou

and 4 more

July 16, 2020
Background: Asthma is a complex chronic inflammatory disorder, with many factors influencing its prevalence. Diet’s impact on the symptoms of the disease is still controversial, although various dietary patterns or specific nutrients have been studied. Objective: The objective of this crossover, randomised, two-period study was to examine the potential of controlling dietary histamine intake and, through this, alter asthma symptoms in children with mild intermittent asthma. Methods: Children with mild intermittent asthma were randomly assigned to either a high- (HH) or low- histamine (LH) diet, based on the Mediterranean pattern, for 4 weeks (t0). This was followed by a 2-week washout period (t1) before patients crossed to the alternative diet (t2) for an additional 4 weeks. Children were assessed at baseline and after the completion of each diet phase. They also recorded symptoms and peak flow throughout the intervention. Adherence to the dietary intervention was assessed via four random 24-hour recalls for each intervention period and comparison of selected qualitative and quantitative indices, i.e. histidine, food choices, energy, macro- and micronutrients intake. Results: Eighteen children (10 boys), with mean age 11,5±3,1years were recruited and completed the study. A trend for prolonged and more severe symptoms was observed during HH. There was good adherence to the diet during remission periods, but lower compliance during symptomatic periods, particularly for the HH group. The mean actual intake differed significantly between the two diets, not only in the histamine content but also in energy, sugar and various micronutrients, including sodium. Conclusions & Clinical Relevance: Diet may have an active and direct impact on asthma symptoms. A diet deviating from the Mediterranean standard in terms of high energy, histamine, and salt has been associated with asthma worsening. Dietary interventions in asthmatic patients should be prospectively evaluated for a longer period and with proper nutritional education.
Convalescent plasma for pediatric patients with COVID-19 associated acute respiratory...
Caroline Diorio
Elizabeth Anderson

Caroline Diorio

and 28 more

July 16, 2020
There are no proven safe and effective therapies for children who develop life-threatening complications of SARS-CoV-2. Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2 but has theoretical risks. We report on the first use of CP in children with life-threatening COVID-19, providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody-dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.
Not all animals are equal - farm living and allergy in Upper Bavaria
Matthias Wjst

Matthias Wjst

July 16, 2020
Background: A lower allergy and asthma prevalence in farm children has been described three decades ago in Switzerland. After years of research into bacterial exposure at farms, the origin of the farm effect is unknown. It could be still the effect of a sampling bias. As there was never any effect in large industrial cattle farms with slatted floors, we now hypothesize that in small farms, where animals are grazing outdoors, children may be exposed to animals with a higher endoparasite load. Methods: We re-analyze an earlier epidemiological study by record-linkage to later agricultural surveys. The Asthma and Allergy Study in 1989/90 was a cross-sectional study of 1714 ten year old children in 63 villages covering ten different districts of Upper Bavaria. The farm effect is defined here as the association of number of cows per villager on lifetime prevalence of allergic rhinitis prevalence in the children. Results: The farm effect is restricted to small villages only. Furthermore, districts with a higher Fasciola infection rates of cows, show a stronger farm effect than districts with lower infection rates. Conclusions: Research into parasite effector molecules is warranted.
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