bluuebunny/crossref_metadata_2025 huggingface dataset:
Larvicidal activity of microparticles of Melissa officinalis L. essential oil (Lamiaceae) against Aedes aegypti (Diptera, Culicidae)
Authors: Martins Thércia Gabrielle Teixeira , Rosa Paulo Victor Serra , Arruda Mariana Oliveira , Dias Andressa Almeida Santana , Araújo Neto Ari Pereira de , Carvalho Ana Maria Almeida Silva , Silveira Leila da Silva , Conceição Francilidia Oliveira Vitorino de Assunção , Conceição Carlos Eduardo Pereira , Sousa Ricardo Teixeira de , Mendes Filho Nestor Everton , Mouchrek Filho Victor Elias , Everton Gustavo Oliveira
Published: January 2021

This study aimed to evaluate the larvicidal activity of essential oil microparticles (EO) of Melissa officinalis L. against Aedes aegypti. The leaves of M. officinalis were collected in the municipality of São José de Ribamar, Maranhão, Brazil, later dried, crushed and ground. 90g of the dried leaves were used to obtain the EO by the hydrodistillation method. For the synthesis of microencapsulated EO, 60g of sodium alginate (2.5% m/v) was added to the mixture of 15g of Tween 20 with 6g of EO. The mixture was homogenized and drips over CaCl2 5% m/v solution for the hardening of particles via crosslinking. The microparticles were washed with distilled water in filter and dried at 35ºC/24h and 15 days at tamb (30ºC). The eggs of Aedes aegypti were collected at the Federal University of Maranhão by the ovitrampas method. The larvae that hatched were fed until they reached the fourth instar. Groups of larvae (n=20) were submitted to solutions of EO and microparticles of 10-90 mg/L . After 24 h, live and dead larvae were counted and LC50 was calculated by the Reed&Muench method, using Cheng's criterion for classification of active potential. All larvae presented mortality in all concentrations tested. The LC50 obtained for the EO was 40.60 mg/L and for the microparticles 22.10 mg/L, both classified as active according to the adopted criterion, but it is observed that the microparticles increased the larvicidal potential of the EO. Through the results obtained, it is concluded that the microparticles formulated with the EO proved to be efficient in the face of the larvae of Aedes aegypti, being interesting and important in controlling and combating the mosquito that transmits dengue.
Uso de biomateriais e rosuvastatina tópica aumenta angiogênese de feridas cirúrgicas em coelhos
Authors: Ferreira Natália Gonzaga de Oliveira , Vicentini Yuri Ferreira , Breda Maria Rosa Santos , Nogueira Rosa Maria Barilli , Nai Gisele Alborguetti , Santarém Cecília Laposy
Published: January 2021

Estudos têm sido realizados para verificar os efeitos de biomateriais, como o plasma rico em plaquetas (PRP) e a fibrina rica em plaquetas (FRP) e a sua contribuição para o processo de cicatrização de feridas por meio da liberação de fatores de crescimento que têm propriedades de indução de regeneração tecidual. Muitas evidências também se mostram favoráveis ao uso tópico da rosuvastatina (RSV) em lesões de pele, por modificar de forma positiva o fluxo sanguíneo basal tecidual. No entanto, não está claro se este efeito está envolvido no aumento do fluxo sanguíneo e por consequência uma melhora no processo cicatricial. Neste sentido, o presente estudo analisou a quantidade de fibroblastos e número de vasos em feridas induzidas experimentalmente em coelhos após tratamento com e sem associação dos biomateriais e RSV. A hipótese baseia-se que o uso tópico de um fármaco hipolipemiante associado a um biomaterial possa aumentar a quantidade de fibroblastos e angiogênese após lesão experimentalmente induzida, e com isso aumentando a colagenização para produção de uma cicatriz mais homogênea. Verificou-se que a associação da FRP e RSV promoveu um efeito aditivo aumentando em 135% a angiogênese. O uso da RSV isolada também proporcionou um aumento de 77% na quantidade de fibroblastos. Concluiu-se que tanto a FRP quanto a RSV possuem bons efeitos cicatrizantes, de tal forma que a associação entre elas foi benéfica e demonstrou um possível efeito aditivo.
Pentoxifylline therapy for patients with type 2 leprosy reactions: erythema nodusum leprosum in steroid-dependent cases
Authors: Djawad Khairuddin
Published: January 2021

Morbus Hansen is an infectious disease which causes by bacilli intracellular Mycobacterium leprae which mainly affects the skin and peripheral nerves. The leprosy reaction is an episode an immunologically mediated episode of acute or sub-acute inflammation that affecting skin, nerve, mucous membrane. Type 2 reactions can be last for months and the risk of developing a dependence on steroids. Pentoxifylline (PTX) works to hampers the production of TNFα in vitro and in vivo as an alternative for ENL treatment.  One case was reported in a male aged 28 years with complaints of recurring red bumps accompanied by fever and pain. On physical examination obtained erythema nodusum, with impaired sensibility in the left leg. The patient experienced improvement after being given therapy of neurodex/24 hours/oral, rifampicin 600mg, ofloxacin 400 mg, minocycline 100 mg which given 3x for a week, and combination therapy to treat the Leprosy reaction given the combination of methylprednisolone 16mg (3-2-0) and Pentoxifylline 400mg/8 hours/oral. In the 21 days of treatment, the redness lump improved in the middle finger and the left arm was gone. No new reddish bumps appeared and less tingling sensation.
Strategy for enhancing KAI Argo Pahrayangan Customers’ loyalty
Authors: Eka F Bertoto , Haryanto Budhi
Published: January 2021

This study aims to know about things that needed to be done to build customer loyalty. Customer loyalty is believed could give a view on the decision to enhance satisfaction and loyalty thus it can be used to make a business strategy. The focus of the study is on the customers of PT. Kereta Api Indonesia (Indonesia Train Company) especially the passenger of Argo Pahrayangan with Jakarta – Bandung route through Gambir Station. Price fairness and service quality become the variable of the study. The methodology used is descriptive qualitative with a library-based approach to analyze customer’s loyalty. The result showed that the higher the level of price fairness, the higher the customer’s satisfaction. It’s possíble to observe that service quality can also affect the customer’s satisfaction. Therefore, in conclusion, both price fairness and service quality are having a significant relationship with customer satisfaction.
The use of Artificial Neural Networks in the diagnosis of manageable factors on Brazilian Primary Health Care
Authors: Cabral Kerla Fabiana Dias , Cerqueira Fábio Ribeiro , Siqueira-Batista Rodrigo , Ferreira Marco Aurélio Marques , Freitas Bruna Rodrigues de
Published: January 2021

The social determinants of health are relevant in the main strategies of Primary Health Care. However, it is known the difficulties of the health sector to overcome the factors that negatively interfere with the health of the population. Thus, it was aimed to create a computer model to present in detail the factors that somehow are related to the Primary Health Care, enabling public health managers to make decisions efficiently. Using artificial neural networks, it was possible to create a classifier model that could show which variables are related to the efficiency in Primary Care and which lead to inefficiency. Moreover, it was used the NICeSim simulator as a tool to evaluate the behavior of each variable identified as relevant to the efficiency in Primary Care of cities. The results demonstrate that the created model was superior to previously proposed models. Furthermore, our model has been demonstrated to be very effective in identifying variables that affect Primary Health. The created model shows that factors, such as illiteracy and welfare programs, considerably affect the efficiency of health care, reinforcing the argument that the focus of the public policies should be dealt in an intersectoral way, improving the factors that positively influence the population health.
Resíduos sólidos urbanos no Estado da Paraíba e o contexto da sustentabilidade ambiental
Authors: Leite Valderi Duarte , Lopes Wilton Silva , Sousa José Tavares de , Albuquerque Maria Virgínia da Conceição , Silva Maria Célia Cavalcante de Paula e , Cartaxo Amanda da Silva Barbosa , Dantas Gabriely Dias
Published: January 2021

Este estudo avaliou a taxa de produção per capita de resíduos sólidos urbanos, bem como identificou os principais mecanismos de disposição final e tratamentos dos resíduos sólidos urbanos coletados do estado da Paraíba. No Brasil a produção per capita de resíduos sólidos urbanos é estimada em 1kg. (hab.dia) -1, sendo produzido diariamente algo em torno de 210 mil toneladas e coletados diariamente em média 172 mil toneladas. Verificou-se que os serviços de limpeza pública, neste estado, do quantitativo dos resíduos sólidos urbanos produzidos, são coletados atualmente algo em torno de 93% e da fração coletada, 40% em média está sendo confinada em aterros sanitários que estão localizados na região metropolitana da cidade de João Pessoa e na cidade de Campina Grande. A quantidade estimada de resíduos sólidos urbanos coletados diariamente é de 2.600 toneladas.dia-1, o que corresponde a um quantitativo de matéria orgânica putrescível de aproximadamente 1.430,000 toneladas.dia-1. Portanto, considerando apenas esta matriz de produção de matéria orgânica putrescível e que esta matéria orgânica será utilizada para produção de composto orgânico, seria produzida um total de 858,0 toneladas de composto orgânico.dia-1, o que propiciaria uma aplicação de 15,9 toneladas de composto orgânico (hab.ano) -1, na área potencialmente agricultável. Pode-se afirmar também, que não é seguro em nenhum aspecto o confinamento de resíduos sólidos urbanos em aterro sanitário, haja vista a complexidade do processo de confinamento em si, a demanda de área requerida e custos financeiros associados, além dos subprodutos gerados e dos impactos ambientais do entorno.
Propriedades ópticas a serem considerados na seleção de cores em Odontologia estética: uma revisão de literatura
Authors: Silva Erika Thaís Cruz da , Silva Adriano Flores da , Costa Suellen Rabelo Rocha da , Bezerra Priscila Lima , Lourenço Aretha Helen Aragão , Pereira Nilson Emmanuel Gomes
Published: January 2021

O objetivo do presente trabalho foi realizar uma revisão de literatura acerca das propriedades ópticas e sua influência na seleção de cores em odontologia estética. Foi realizada uma revisão de estudos disponíveis na literatura por meio da busca bibliográfica nas bases de dados eletrônicos Pubmed/Medline, Lilacs, Science direct e Scielo (scientific eletronic library). para a pesquisa foram utilizados os seguintes descritores: “propriedades ópticas”, “odontologia estética”, “seleção de cores” e “fluorescência”. Os artigos foram selecionados obedecendo-se aos critérios de inclusão e exclusão do estudo. Também foram adicionados alguns livros com conteúdos relevantes para esta pesquisa. Assim como, foi indispensável à disponibilidade do texto integral para sua inclusão no estudo.  A escolha correta da cor é o processo que representa uma das maiores dificuldades dos profissionais, pois não depende apenas da técnica e da experiência profissional, mas também de uma série de fatores relacionados ao meio em que estão inseridos os dentes. As propriedades ópticas apresentam grande relevância na seleção de cores em procedimentos estéticos na odontologia. É importante que o profissional conheça essas propriedades e aplique esses conhecimentos na prática clínica diária para que obtenha os melhores resultados possíveis em seus casos.
The biocompatibility of Achyrocline satureioides plant extract over human gingival fibroblasts
Authors: Ferreira Elis Cecília Castro , Gonçalves Taciano Moreira , Pereira Thaís Cristine , Hasna Amjad Abu , Oliveira Felipe Eduardo de , Jorjão Adeline Lacerda , Camargo Samira Esteves Afonso , Oliveira Luciane Dias de , Spalding Marianne
Published: January 2021

Objective: Achyrocline satureioides “A.satureioides” is a subshrub, widely distributed in South America because of its medicinal properties. Although it is widely used in folk medicine, there is still no approval for its therapeutic use, and its biocompatibility is little explored.  This study aimed to evaluate its cytotoxicity and genotoxicity over human gingival fibroblasts (FMM-1). Methodology: Ten different concentration of the glycolic extract of A.satureioides were tested for 5min and 24h of contact with the cells to evaluate its cytotoxicity using the MTT colorimetric assay and to evaluate its genotoxicity using the micronucleus assay. Data were analyzed with one-way ANOVA and Tukey test with a significance level (α=0.05). Results: All tested concentrations of the extract presented cell viability more than 70% and has no significant difference of the control group after 5min and 24h. However, for 5min the 100 mg/mL was cytotoxic and for 24h the 1.56 mg/mL stimulated cell proliferation. For genotoxicity analysis, only the concentration 6.25 mg/mL showed results similar to the control of cell culture in the micronucleus count after 5min and 24h. Conclusions: The glycolic extract of A.satureioides doesn’t have cytotoxic and genotoxic effects in concentrations up to 6.25 mg/mL, but in high concentrations it is considered genotoxic.
Veche and the terms “All Pskov” and “Pskov Men”: The Russian Medieval City Assembly as a Communal Structure
Authors: Vovin Alexei A.
Published: January 2021

The article focuses on the collective political institution, the veche, of the Russian medieval city of Pskov. The author argues that the horizontal political ties within that city prevailed over the vertical ones in the period before its subjugation to the Muscovite State in 1510. Pskov is put into a broad comparative perspective which results in the conclusion by the author that the development of Pskov in the fourteenth–fifteenth centuries very closely resembled that kind of urban synoecism which was practiced by Western European communes in their early stage of development (eleventh–twelfth centuries). It means, first, that the Russian Middle Ages repeated in some important features that which had occurred in Western Europe, and, second, that it happened not due to a borrowing of political institutions (as was the case with many East European countries) but independently because of similar conditions arising, albeit after a two-century delay.
Vasorelaxing Action of Vasonatrin Peptide is Associated with
Activation of Large-Conductance Ca2+-activated Potassium Channels
in Vascular Smooth Muscle Cells
Authors: Yu J , Zhu M , Fu Z , Zhu X , Zhao Y , Chen B
Published: January 2021

The aim of this study was to test the hypothesis that
vasorelaxing action of vasonatrin peptide (VNP) is due to
activation of the large-conductance Ca2+-activated potassium
channel (BKCa) via guanylyl cyclase (GC)-coupled natriuretic
peptide receptors (NPRs) in vascular smooth muscle cells
(VSMCs). Contraction experiments were performed using human
radial artery, whereas BKCa current by patch clamp was recorded
in cells from rat mesenteric artery. Contractility of rings cut from
human radial artery was detected in vitro. As a result, VNP
induced a dose-dependent vasorelaxation of human radial artery,
which could be mimicked by 8-Br-cGMP, and suppressed by TEA,
a blocker of BKCa, HS-142-1, a blocker of GC-coupled NPRs, or
methylene blue (MB), a selective inhibitor of guanylyl cyclase.
Sequentially, whole-cell K+ currents were recorded using patch
clamp techniques. BKCa current of VSMCs isolated from rat
mesentery artery was obtained by subtracting the whole cell
currents after applications of 10-7 mol/l iberiotoxin (IBX) from
before its applications. In accordance with the results of arterial
tension detection, BKCa current was significantly magnified by
VNP, which could also be mimicked by 8-Br-cGMP, whereas
suppressed by HS-142-1, or MB. Taken together, VNP acts as a
potent vasodilator, and NPRA/B-cGMP-BKCa is one possible
signaling system involved in VNP induced relaxation.
Holism and Life Manifestations: Molecular and Space-Time Biology
Authors: Křeček J
Published: January 2021

Appeals of philosophers to look for new concepts in sciences are
being met with a weak response. Limited attention is paid to the
relation between synthetic and analytic approach in solving
problems of biology. An attempt is presented to open a
discussion on a possible role of holism. The term “life
manifestations” is used in accordance with phenomenology.
Multicellular creatures maintain milieu intérieur to keep an
aqueous milieu intracellulair in order to transform the energy of
nutrients into the form utilizable for driving cellular life
manifestations. Milieu intérieur enables to integrate this kind of
manifestations into life manifestations of the whole multicellular
creatures. The integration depends on a uniqueness and
uniformity of the genome of cells, on their mutual recognition
and adherence. The processes of ontogenetic development
represent the natural mode of integration of cellular life
manifestations. Functional systems of multicellular creatures are
being established by organization of integrable cells using a wide
range of developmental processes. Starting from the zygote
division the new being displays all properties of a whole creature,
although its life manifestations vary. Therefore, the whole
organism is not only more than its parts, as supposed by holism,
but also more than developmental stages of its life
manifestations. Implicitly, the units of whole multicellular
creature are rather molecular and developmental events than the
cells per se. Holism, taking in mind the existence of molecular
and space-time biology, could become a guide in looking for a
new mode of the combination of analytical and synthetic
reasoning in biology.
Into the Warm Zone: Essential Elements and Considerations for Developing Warm Zone Capabilities
Authors: Miletta Sam
Published: January 2021

In 2017, a scholarship funded study tour was undertaken to learn how agencies in the United States of America were addressing a capability gap in relation to accessing, treatment and rescue of victims located in the warm zone of Active Shooter Hostile Events. Since this initial trip a number of after action reports and reviews of such incidents have been released. This paper explores the key learnings from these events to establish several essential elements and important considerations for the development of multi-agency warm zone capabilities. The incidents looked at are the:

2013 LAX Airport Active Shooter

2015 San Bernardino Terrorist Attack

2016 Pulse Nightclub Terrorist Attack

2017 Las Vegas Mass Shooting
INFLUENCE OF METHOD OF LEARNING AND SKILLS SELF- CONFIDENCE OF SCIENCE PROCESS SKILLS IN CLASS V ELEMENTARY SCHOOL OF CITY OF SERANG
Authors: M.P Fahrudin
Published: January 2021

This research discusses the influence of teaching methods and ability of self- confidence of the science process skills. This research was conducted at the State Elementary School fifth grade of City of Serang. The study design using analysis of variance 2 lanes (ANOVA). The results of this study were (1) the difference in science process skills of elementary school students who learn using Discovery methods between students who learn using Inquiry methods (2) The interaction between  the  learning  methods  and  self-confidence  of  students  to  the  science process skills Elementary School Students. (3) The science process skills between student elementary school students who learn by using Discovery methods which has self-confidence high is higher result than the students who learned by using Inquiry methods who has self-confidence high  (4) The science process skills of elementary school students between students who learn to use Discovery methods that have self-confidence low is lower result than the students learn to use the Inquiry methods that has self-confidence low
Kurikulum Multikulturalisme Untuk Pendidikan Berkeadilan
Authors: Tasrif Tasrif
Published: January 2021

Multikultural adalah khazanah bangsa dan dunia. Multikulturalism

harus menjadi dasar filosofis dalam membuat kebijakan dan perencanaan

pendidikan. Pendidikan belum sepenuhnya berwajah multikultural. Nilai-nilai

multikultur harus mengejewantah ke semua aspek kehidupan berbangsa dan

bernegara. Kebijakan pendidikan yang tidak mengadopasi nilai-nilai

multikulturalisme menyisahkan disparitas pendidikan antara pusat dan daerah,

suku satu dengan lain. Sekolah menyambut dan menyediakan siswa yang berasal

dari latar belakang budaya yang berbeda. Sekolah dan pendidik harus responsif

secara cultural sebagai bentuk penghormatan terhadap pendidikan multikultural.

Pendidikan multikultural adalah pendekatan progresif, alat untuk

mentransformasikan pendidikan yang mengkritisi dan memperbaiki literasi rasial

dan kebijakan yang diskriminatif di dalam pendidikan. Kurikulum yang

multikultur harus diterapkan untuk menguatkan cita-cita keadilan sosial.
Modulation of IMD, Toll, and Jak/STAT Immune Pathways Genes in the Fat Body of Rhodnius prolixus During Trypanosoma rangeli Infection
Authors: Rolandelli Agustín , Nascimento Adeisa E. C. , Silva Leticia S. , Rivera-Pomar Rolando , Guarneri Alessandra A.
Published: January 2021

Trypanosoma rangeli is the second most common American trypanosome that infects man. It is vectored by triatomines from the genus Rhodnius, in which it invades the hemolymph and infects the salivary glands, avoiding the bug immune responses. In insects, these responses are initiated by well conserved pathways, mainly the IMD, Toll, and Jak/STAT. We hypothesize that long-term infection with T. rangeli in the gut or hemolymph of Rhodnius prolixus triggers different systemic immune responses, which influence the number of parasites that survive inside the vector. Thus, we investigated groups of insects with infections in the gut and/or hemolymph, and evaluated the parasite load and the expression in the fat body of transcription factors (Rp-Relish, Rp-Dorsal, and Rp-STAT) and inhibitors (Rp-Cactus and Rp-Caspar) of the IMD, Toll, and Jak/STAT pathways. We detected lower parasite counts in the gut of insects without hemolymph infection, compared to hemolymph-infected groups. Besides, we measured higher parasite numbers in the gut of bugs that were first inoculated with T. rangeli and then fed on infected mice, compared with control insects, indicating that hemolymph infection increases parasite numbers in the gut. Interestingly, we observed that genes from the three immune pathways where differentially modulated, depending on the region parasites were present, as we found (1) Rp-Relish downregulated in gut-and/or-hemolymph-infected insects, compared with controls; (2) Rp-Cactus upregulated in gut-infected insect, compared with controls and gut-and-hemolymph-infected groups; and (3) Rp-STAT downregulated in all groups of hemolymph-infected insects. Finally, we uncovered negative correlations between parasite loads in the gut and Rp-Relish and Rp-Cactus expression, and between parasite counts in the hemolymph and Rp-Relish levels, suggesting an association between parasite numbers and the IMD and Toll pathways. Overall, our findings reveal new players in R. prolixus–T. rangeli interactions that could be key for the capacity of the bug to transmit the pathogen.
Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids
Authors: Dahlstrand Rudin Agnes , Khamzeh Arsham , Venkatakrishnan Vignesh , Persson Tishana , Gabl Michael , Savolainen Otto , Forsman Huamei , Dahlgren Claes , Christenson Karin , Bylund Johan
Published: January 2021

Neutrophil migration from blood to tissue-residing microbes is governed by a series of chemoattractant gradients of both endogenous and microbial origin. Periodontal disease is characterized by neutrophil accumulation in the gingival pocket, recruited by the subgingival biofilm consisting mainly of gram-negative, anaerobic and proteolytic species such asPorphyromonas gingivalis. The fact that neutrophils are the dominating cell type in the gingival pocket suggests that neutrophil-specific chemoattractants are released by subgingival bacteria, but characterization of chemoattractants released by subgingival biofilm species remains incomplete. In the present study we characterized small (< 3 kDa) soluble chemoattractants released by growingP. gingivalis, and show that these are selective for neutrophils. Most neutrophil chemoattractant receptors are expressed also by mononuclear phagocytes, the free fatty acid receptor 2 (FFAR2) being an exception. In agreement with the selective neutrophil recruitment, the chemotactic activity found inP. gingivalissupernatants was mediated in part by a mixture of short chain fatty acids (SCFAs) that are recognized by FFAR2, and other leukocytes (including monocytes) did not respond to SCFA stimulation. Although SCFAs, produced by bacterial fermentation of dietary fiber in the gut, has previously been shown to utilize FFAR2, our data demonstrate that the pronounced proteolytic metabolism employed byP. gingivalis(and likely also other subgingival biofilm bacteria associated with periodontal diseases) may result in the generation of SCFAs that attract neutrophils to the gingival pocket. This finding highlights the interaction between SCFAs and FFAR2 in the context ofP. gingivaliscolonization during periodontal disease, but may also have implications for other inflammatory pathologies involving proteolytic bacteria.
Genomic Characterization of WRKY Transcription Factors Related to Andrographolide Biosynthesis in Andrographis paniculata
Authors: Zhang Rongrong , Chen Zhenzhen , Zhang Libing , Yao Wei , Xu Zhichao , Liao Baosheng , Mi Yaolei , Gao Han , Jiang Chunhong , Duan Lixin , Ji Aijia
Published: January 2021

Andrographolide, which is enriched in the leaves of Andrographis paniculata, has been known as “natural antibiotic” due to its pharmacological activities such as anti-inflammatory, antimicrobial and antioxidant effects. Several key enzymes in andrographolide biosynthetic pathway have been studied since the genome sequences were released, but its regulatory mechanism remains unknown. WRKY transcription factors proteins have been reported to regulate plant secondary metabolism, development as well as biotic and abiotic stresses. Here, WRKY transcription factors related to andrographolide biosynthesis were systematically identified, including sequences alignment, phylogenetic analysis, chromosomal distribution, gene structure, conserved motifs, synteny, alternative splicing event and Gene ontology (GO) annotation. A total of 58 WRKYs were identified in Chuanxinlian genome and phylogenetically classified into three groups. Moreover, nine WRKY genes underwent alternative splicing events. Furthermore, the combination of binding site prediction, gene-specific expression patterns, and phylogenetic analysis suggested that 7 WRKYs (ApWRKY01, ApWRKY08, ApWRKY12, ApWRKY14, ApWRKY19, ApWRKY20, and ApWRKY50) might regulate andrographolide biosynthesis. This study laid a foundation for understanding the regulatory mechanism of andrographolide biosynthesis and the improvement and breeding of Andrographis paniculata varieties.
Acute Functional Outcomes in Critically Ill COVID-19 Patients
Authors: Tay Matthew Rong Jie , Ong Poo Lee , Puah Ser Hon , Tham Shuen Loong
Published: January 2021

Background:COVID-19 (Coronavirus Disease 2019) is a global cause of morbidity and mortality currently. We aim to describe the acute functional outcomes of critically ill coronavirus disease 2019 (COVID-19) patients after transferring out of the intensive care unit (ICU).

Methods:51 consecutive critically ill COVID-19 patients at a national designated center for COVID-19 were included in this exploratory, retrospective observational cohort study from January 1 to May 31, 2020. Demographic and clinical data were collected and analyzed. Functional outcomes were measured primarily with the Functional Ambulation Category (FAC), and divided into 2 categories: dependent ambulators (FAC 0–3) and independent ambulators (FAC 4–5). Multivariate analysis was performed to determine associations.

Results:Many patients were dependent ambulators (47.1%) upon transferring out of ICU, although 92.2% regained independent ambulation at discharge. On multivariate analysis, we found that a Charlson Comorbidity Index of 1 or more (odds ratio 14.02, 95% CI 1.15–171.28,P= 0.039) and a longer length of ICU stay (odds ratio 1.50, 95% CI 1.04–2.16,P= 0.029) were associated with dependent ambulation upon discharge from ICU.

Conclusions:Critically ill COVID-19 survivors have a high level of impairment following discharge from ICU. Such patients should be screened for impairment and managed appropriately by rehabilitation professionals, so as to achieve good functional outcomes on discharge.
Study on Circulating Antigens in Serum of Mice With Experimental Acute Toxoplasmosis
Authors: Liu Qi , Jiang Wei , Chen Yun , Zhang Manyu , Geng Xiaoling , Wang Quan
Published: January 2021

Toxoplasma gondii is a ubiquitous apicomplexan protozoan parasite that can infect all warm-blooded animals, causing toxoplasmosis. Thus, efficient diagnosis methods for acute T. gondii infection are essential for its management. Circulating antigens (CAgs) are reliable diagnostic indicators of acute infection. In this study, we established a mouse model of acute T. gondii infection and explored new potential diagnostic factors. CAgs levels peaked 60 h after T. gondii inoculation and 31 CAgs were identified by immunoprecipitation-liquid chromatography-tandem mass spectrometry, among which RuvB-like helicase (TgRuvBL1), ribonuclease (TgRNaseH1), and ribosomal protein RPS2 (TgRPS2) were selected for prokaryotic expression. Polyclonal antibodies against these three proteins were prepared. Results from indirect enzyme-linked immunosorbent assay indicated that anti-rTgRuvBL1, anti-rTgRNase H1, and anti-rTgRPS2 mouse sera were recognized by natural excretory-secretory antigens from T. gondii tachyzoites. Moreover, immunofluorescence assays revealed that TgRuvBL1 was localized in the nucleus, while TgRNase H1 and TgRPS2 were in the apical end. Western blotting data confirmed the presence of the three proteins in the sera of the infected mice. Moreover, mice immunized with rTgRuvBL1 (10.0 ± 0.30 days), TgRNaseH1 (9.67 ± 0.14 days), or rTgRPS2 (11.5 ± 0.34 days) had slightly longer lifespan when challenged with a virulent T. gondii RH strain. Altogether, these findings indicate that these three proteins can potentially be diagnostic candidates for acute toxoplasmosis. However, they hold poor protective potential against highly virulent T. gondii infection.
Sleep Disturbance is Associated With Higher Plasma Aβ Levels in Cognitively Normal Adults—A Population-Based Cross-Sectional Study
Authors: Gao Yao , Wei Shan , Gao Fan , Gao Ling , Dang Liangjun , Shang Suhang , Chen Chen , Huo Kang , Wang Jingyi , Wang Jin , Qu Qiumin
Published: January 2021

Objective: Growing evidence suggests that sleep disturbance is a risk factor for Alzheimer's disease (AD). Amyloid-β (Aβ) deposition in the brain is a main pathophysiology of AD. Considering that peripheral Aβ level is associated with brain Aβ deposition, the present study investigated the relationship between sleep disturbance and plasma Aβ levels.

Methods: This is a population-based cross-sectional study. A total of 1,459 participants from a village in the suburbs of Xi'an, China, were enrolled from January 3, 2017 to March 26, 2017. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and a PSQI score of <5 points was considered as good sleep quality and a PSQI score of >10 points as poor sleep quality. Cognitive function was assessed with the Mini-Mental State Examination (MMSE). Fasting venous blood was taken in the morning, and the plasma Aβ levels were measured using ELISA. The relationships between plasma Aβ levels and sleep quality were analyzed using multiple linear regression.

Results: Among the participants, 231 had poor sleep quality (15.83%). The log-transformed Aβ40 level had significant differences among the different sleep groups (F = 3.216, p = 0.040). The log-transformed Aβ40 level was higher in the poor sleep quality group than that in the general sleep quality group [87.17 (73.42, 107.34) vs. 89.69 (74.81, 125.79) pg/ml, p = 0.016]. In bivariate analysis, sleep quality was negatively associated with the log-transformed plasma Aβ40 level (β = −0.025, p = 0.011).

Conclusion: In the community population, poorer sleep quality is associated with a higher plasma Aβ40 level. This indicated that sleep disturbance might also involve in dysfunction of peripheral Aβ clearance.
Putative Activation of the CB1 Cannabinoid Receptors Prevents Anxiety-Like Behavior, Oxidative Stress, and GABA Decrease in the Brain of Zebrafish Submitted to Acute Restraint Stress
Authors: Lucas Luz Waldo , Santos-Silva Mateus , Cardoso Patrick Bruno , Assad Nadyme , Moraes Edinaldo Rogério da Silva , Grisólia Alan Barroso Araújo , Braga Danielle Valente , Leão Luana Ketlen Reis , Moraes Suellen Alessandra Soares de , Passos Adelaide da Conceição , Batista Evander de Jesus Oliveira , Gouveia Amauri , Oliveira Karen R. H. Matos , Herculano Anderson Manoel
Published: January 2021

Anxiety disorder is a well-recognized condition observed in subjects submitted to acute stress. Although the brain mechanisms underlying this disorder remain unclear, the available evidence indicates that oxidative stress and GABAergic dysfunction mediate the generation of stress-induced anxiety. Cannabinoids are known to be efficient modulators of behavior, given that the activation of the cannabinoid receptors type-1 (CB1 receptors) induces anxiolytic-like effects in animal models. In the present study, we aimed to describe the effects of the stimulation of the CB1 receptors on anxiety-like behavior, oxidative stress, and the GABA content of the brains of zebrafish submitted to acute restraint stress (ARS). The animals submitted to the ARS protocol presented evident anxiety-like behavior with increased lipid peroxidation in the brain tissue. The evaluation of the levels of GABA in the zebrafish telencephalon presented decreased levels of GABA in the ARS group in comparison with the control. Treatment with ACEA, a specific CB1 receptor agonist, prevented ARS-induced anxiety-like behavior and oxidative stress in the zebrafish brain. ACEA treatment also prevented a decrease in GABA in the telencephalon of the animals submitted to the ARS protocol. Overall, these preclinical data strongly suggest that the CB1 receptors represent a potential target for the development of the treatment of anxiety disorders elicited by acute stress.
Can GLP-1 Be a Target for Reward System Related Disorders? A Qualitative Synthesis and Systematic Review Analysis of Studies on Palatable Food, Drugs of Abuse, and Alcohol
Authors: Eren-Yazicioglu Candan Yasemin , Yigit Arya , Dogruoz Ramazan Efe , Yapici-Eser Hale
Published: January 2021

The role of glucagon-like peptide 1 (GLP-1) in insulin-dependent signaling is well-known; GLP-1 enhances glucose-dependent insulin secretion and lowers blood glucose in diabetes. GLP-1 receptors (GLP-1R) are also widely expressed in the brain, and in addition to its role in neuroprotection, it affects reward pathways. This systematic review aimed to analyze the studies on GLP-1 and reward pathways and its currently identified mechanisms.

Methods: “Web of Science” and “Pubmed” were searched to identify relevant studies using GLP-1 as the keyword. Among the identified 26,539 studies, 30 clinical, and 71 preclinical studies were included. Data is presented by grouping rodent studies on palatable food intake, drugs of abuse, and studies on humans focusing on GLP-1 and reward systems.

Results: GLP-1Rs are located in reward-related areas, and GLP-1, its agonists, and DPP-IV inhibitors are effective in decreasing palatable food intake, along with reducing cocaine, amphetamine, alcohol, and nicotine use in animals. GLP-1 modulates dopamine levels and glutamatergic neurotransmission, which results in observed behavioral changes. In humans, GLP-1 alters palatable food intake and improves activity deficits in the insula, hypothalamus, and orbitofrontal cortex (OFC). GLP-1 reduces food cravings partially by decreasing activity to the anticipation of food in the left insula of obese patients with diabetes and may inhibit overeating by increasing activity to the consumption of food in the right OFC of obese and left insula of obese with diabetes.

Conclusion: Current preclinical studies support the view that GLP-1 can be a target for reward system related disorders. More translational research is needed to evaluate its efficacy on human reward system related disorders.
Serum Tumor Markers in Paraneoplastic Neurologic Syndromes: A Systematic Review of Guidelines
Authors: Trevisiol Chiara , Cani Ilaria , Fabricio Aline S. C. , Gion Massimo , Giometto Bruno , De Massis Patrizia
Published: January 2021

Purpose: Algorithms for the detection of a malignancy in patients with unclear neurologic symptoms of suspicious paraneoplastic origins are not universally applied. Frequently, circulating tumor markers (TMs) are considered a valuable tool for cancer diagnosis in patients with paraneoplastic neurologic syndromes (PNS). Our aim was to extract the recommendations on the use of TMs and onconeural antibodies (Abs) for the diagnosis of malignancies in PNS from clinical practice guidelines and put them forward as evidence in a common framework to facilitate diffusion, dissemination, and implementation.

Methods: Systematic literature searches were performed for guidelines on both oncology and PNS published since 2007. Guidelines containing information and recommendations for clinical practice pertaining to the screening and diagnosis of PNS were selected. Information on circulating TMs and onconeural Abs was extracted and synthesized in consecutive steps of increasing simplification.

Results: We retrieved 799 eligible guidelines on oncology for the potential presence of information on PNS but only six covered treated diagnosis or the screening of cancer in PNS, which were then selected. Seventy-nine potentially relevant guidelines on PNS were identified as eligible and 15 were selected. Synoptic tables were prepared showing that classical TMs are not recommended for the screening or the diagnosis of a malignancy in patients with a suspected PNS. Neither should onconeural Abs be considered to screen for the presence of a malignancy, although they could be helpful to define the probability of the paraneoplastic origin of a neurologic disorder.

Conclusion: The present work of synthesis may be a useful tool in the diffusion, dissemination, and implementation of guideline recommendations, potentially facilitating the decrease of the inappropriate use of circulating biomarkers for cancer screening in the presence of PNS.
Respiratory Syncytial Virus Bronchiolitis in Infancy: The Acute Hospitalization Cost
Authors: Bozzola Elena , Ciarlitto Claudia , Guolo Stefano , Brusco Carla , Cerone Gennaro , Antilici Livia , Schettini Livia , Piscitelli Anna Lucia , Chiara Vittucci Anna , Cutrera Renato , Raponi Massimiliano , Villani Alberto
Published: January 2021

Introduction: Respiratory syncytial virus (RSV) bronchiolitis is among the leading causes of hospitalization in infants. Prophylaxis with palivizumab may reduce RSV infection, but its prescription is restricted to high-risk groups. The aim of the study is to retrospectively determine acute hospitalization costs of bronchiolitis.

Materials and methods: Infants aged 1 month−1 year, admitted to Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of bronchiolitis from January 1 till December 31, 2017, were included in the study.

Results: A total of 531 patients were enrolled in the study, and the mean age was 78.75 days. The main etiologic agent causing bronchiolitis was RSV, accounting for 58.38% of infections. The total cost of bronchiolitis hospitalization was 2,958,786 euros. The mean cost per patient was significantly higher in the case of RSV (5,753.43 ± 2,041.62 euros) compared to other etiology (5,395.15 ± 2,040.87 euros) (p = 0.04).

Discussion: The study confirms the high hospitalization cost associated with bronchiolitis. In detail, in the case of RSV etiology, the cost was higher compared to other etiology, which is likely due to the longer hospitalization and the more frequent admission to the intensive cure department.

Conclusion: This study highlights that bronchiolitis is an important cost item even in a tertiary hospital and that cost-effective interventions targeting RSV are increasingly urgent.
Effects of Simulated Microgravity on Ultrastructure and Apoptosis of Choroidal Vascular Endothelial Cells
Authors: Zhao Hongwei , Shi Yuanyuan , Qiu Changyu , Zhao Jun , Gong Yubo , Nie Chuang , Wu Bin , Yang Yanyan , Wang Fei , Luo Ling
Published: January 2021

Background

It was confirmed that simulated microgravity (SMG) led to ultrastructural alterations and apoptosis in many types of microvascular endothelial cells. However, whether SMG would also affect choroidal vascular endothelial cells (CVECs) remains unknown. This study was designed to investigate the effects of SMG on ultrastructure and apoptosis of CVECs.

Methods

The rotary cell culture system (RCCS) was utilized to simulate microgravity condition. Human CVECs were cultured under normal gravity (NG) or SMG condition for 3 days. The ultrastructure was viewed under transmission electron microscopy, and the organization of F-actin was observed by immunofluorescence staining. Additionally, the apoptosis percentage was calculated using flow cytometry. Moreover, the mRNA and protein expression of BAX, Bcl-2, Caspase3, Cytochrome C, p-AKT, and p-PI3K were detected with quantitative PCR and Western blot at different exposure time.

Results

In the SMG group, CVECs presented with a shrunk cell body, chromatin condensation and margination, mitochondria vacuolization, and apoptotic bodies. The amount of F-actin decreased, and the filaments of F-actin were sparse or even partly discontinuous after cultivation under SMG for 72 h. The proportions of apoptotic CVECs in SMG groups at 24 and 72 h were significantly higher than those in the NG group (P < 0.001). The mRNA and protein expression of Bax, Caspase3, and Cytochrome C of CVECs in SMG groups at 24 and 72 h significantly increased than those of the NG group, respectively (P < 0.001). The alterations of p-AKT and p-PI3K protein expression possessed similar trends. On the contrary, the mRNA and protein expression of Bcl-2 in CVECs under SMG at 24 and 72 h were significantly less than that of the NG group, respectively (P < 0.001).

Conclusion

Simulated microgravity conditions can lead the alterations of the F-actin structure and apoptosis of CVECs. The Bcl-2 apoptosis pathway and PI3K/AKT pathway may participate in the damage of CVECs caused by SMG.
Repositioning Drugs on Human Influenza A Viruses Based on a Novel Nuclear Norm Minimization Method
Authors: Liang Hang , Zhang Li , Wang Lina , Gao Man , Meng Xiangfeng , Li Mengyao , Liu Junhui , Li Wei , Meng Fanzheng
Published: January 2021

Influenza A viruses, especially H3N2 and H1N1 subtypes, are viruses that often spread among humans and cause influenza pandemic. There have been several big influenza pandemics that have caused millions of human deaths in history, and the threat of influenza viruses to public health is still serious nowadays due to the frequent antigenic drift and antigenic shift events. However, only few effective anti-flu drugs have been developed to date. The high development cost, long research and development time, and drug side effects are the major bottlenecks, which could be relieved by drug repositioning. In this study, we proposed a novel antiviral Drug Repositioning method based on minimizing Matrix Nuclear Norm (DRMNN). Specifically, a virus-drug correlation database consisting of 34 viruses and 205 antiviral drugs was first curated from public databases and published literature. Together with drug similarity on chemical structure and virus sequence similarity, we formulated the drug repositioning problem as a low-rank matrix completion problem, which was solved by minimizing the nuclear norm of a matrix with a few regularization terms. DRMNN was compared with three recent association prediction algorithms. The AUC of DRMNN in the global fivefold cross-validation (fivefold CV) is 0.8661, and the AUC in the local leave-one-out cross-validation (LOOCV) is 0.6929. Experiments have shown that DRMNN is better than other algorithms in predicting which drugs are effective against influenza A virus. With H3N2 as an example, 10 drugs most likely to be effective against H3N2 viruses were listed, among which six drugs were reported, in other literature, to have some effect on the viruses. The protein docking experiments between the chemical structure of the prioritized drugs and viral hemagglutinin protein also provided evidence for the potential of the predicted drugs for the treatment of influenza.
Dynamic RNA Regulation in the Brain Underlies Physiological Plasticity in a Hibernating Mammal
Authors: Fu Rui , Gillen Austin E. , Grabek Katharine R. , Riemondy Kent A. , Epperson L. Elaine , Bustamante Carlos D. , Hesselberth Jay R. , Martin Sandra L.
Published: January 2021

Hibernation is a physiological and behavioral phenotype that minimizes energy expenditure. Hibernators cycle between profound depression and rapid hyperactivation of multiple physiological processes, challenging our concept of mammalian homeostasis. How the hibernator orchestrates and survives these extremes while maintaining cell to organismal viability is unknown. Here, we enhance the genome integrity and annotation of a model hibernator, the 13-lined ground squirrel. Our new assembly brings this genome to near chromosome-level contiguity and adds thousands of previously unannotated genes. These new genomic resources were used to identify 6,505 hibernation-related, differentially-expressed and processed transcripts using RNA-seq data from three brain regions in animals whose physiological status was precisely defined using body temperature telemetry. A software tool, squirrelBox, was developed to foster further data analyses and visualization. SquirrelBox includes a comprehensive toolset for rapid visualization of gene level and cluster group dynamics, sequence scanning of k-mer and domains, and interactive exploration of gene lists. Using these new tools and data, we deconvolute seasonal from temperature-dependent effects on the brain transcriptome during hibernation for the first time, highlighting the importance of carefully timed samples for studies of differential gene expression in hibernation. The identified genes include a regulatory network of RNA binding proteins that are dynamic in hibernation along with the composition of the RNA pool. In addition to passive effects of temperature, we provide evidence for regulated transcription and RNA turnover during hibernation. Significant alternative splicing, largely temperature dependent, also occurs during hibernation. These findings form a crucial first step and provide a roadmap for future work toward defining novel mechanisms of tissue protection and metabolic depression that may 1 day be applied toward improving human health.