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This article investigates the international panorama of the implementation of Emergency Income in context of the Coronavirus pandemic. To this, we use: a) the database of Social Protection and Jobs Responses to Covid-19 (World Bank) produced from the survey on 5 continents; (b) data from newspaper articles around the world and c) data from the official websites of local governments in different regions of the globe. Particularly in Brazil, we found several adversities of this emergency policy: the long lines for registration of the benefit generating agglomeration; initial difficulties regarding non-regularized CPF; the delay in making the decision to pay the aid; the precariousness of human resources; little familiarity with digital technologies among the poorest population; and the problems of horizontal and vertical inefficiency. Lastly, this study aims to bring contributions to the conflictual relation between State and Society in times of health crisis., Este artigo investiga o panorama internacional da implementação do Auxílio Emergencial no contexto da pandemia do Coronavírus. Para tanto, utilizamos: a) a base de dados do Social Protection and Jobs Responses to Covid-19 (Banco Mundial) produzida a partir do levantamento em 5 continentes; b) os dados provenientes de matérias de jornais ao redor do mundo e c) dados dos sites oficiais dos governos locais em diferentes regiões do globo. Em particular no Brasil, encontramos várias adversidades dessa política emergencial: as longas filas para cadastramento do benefício gerando aglomeração; dificuldades iniciais quanto ao CPF não regularizado; a demora na tomada de decisão para o pagamento do auxílio; a precariedade dos recursos humanos; pouco conhecimento com as tecnologias digitais entre a população mais vulnerável e os problemas de ineficiências horizontal e vertical. Por fim, este estudo pretende trazer contribuições à relação conflituosa entre Estado e Sociedade em tempo de crise sanitária.

OBJETIVO: o presente objetiva caracterizar o impacto dos óbitos em decorrência da dengue no Brasil nos últimos dez anos. MÉTODOS: para estimativa do impacto socioeconômico, utilizou-se a variável Anos Potenciais de Vida Perdidos (APVP), estabelecendo-se como limite para o cálculo a idade de 75 anos. Foram selecionados os dados referentes aos óbitos por dengue no Brasil no período de 2009 a 2018. RESULTADOS: o número de óbitos notificados de indivíduos até 75 anos, em decorrência da dengue foi de 4.295, totalizando 144.301 APVP. A dengue, apesar de ser uma doença negligenciada, gera perdas econômicas elevadas ao país, as maiores dentre o Hemisfério Ocidental. CONCLUSÃO: destarte, é imprescindível aumentar os investimentos nessa temática, de forma a permitir profilaxia e manejo adequados dessa condição, para que seja possível fortalecer estratégias com potencial para minimização da morbimortalidade pela doença.

Summary The PALM trial in the Democratic Republic of the Congo identified a statistically significant survival benefit for two monoclonal antibody-based therapeutics in the treatment of acute Ebola virus disease; however, substantial gaps remain in improving the outcomes of acute Ebola virus disease and for the survivors. Ongoing efforts are needed to develop more effective strategies, particularly for individuals with severe disease, for prevention and treatment of viral persistence in immune-privileged sites, for optimisation of post-exposure prophylaxis, and to increase therapeutic breadth. As antibody-based approaches are identified and advanced, promising small-molecule antivirals currently in clinical stage development should continue to be evaluated for filovirus diseases, with consideration of their added value in combination approaches with bundled supportive care, their penetration in tissues of interest, the absence of interaction with glycoprotein-based vaccines, and filoviral breadth.

Os gatos, por apresentarem limiar de estresse muito baixo, manifestam durante as consultas parâmetros vitais alterados. sobre a fisiologia do estresse na qual aborda as principais alterações que podem ser encontradas em detrimento deste fenômeno. O presente estudo avaliou os parâmetros clínicos de frequência cardíaca, frequência respiratória e temperatura corporal de gatos, sob condições naturais de estresse, atendidos em ambiente ambulatorial na Clínica Veterinária Universitária da Universidade Federal do Tocantins e os correlacionou às variáveis temperatura ambiente, umidade ambiente e momento da aferição desses parâmetros clínicos (início ou final da consulta). Não houve correlação significativa entre temperatura corporal e temperatura ambiente, o que pode sugerir uma boa adaptação dos gatos que vivem na região de Araguaína a altas temperaturas. A frequência respiratória apresentou valores médios superiores aos descritos pela literatura (p

Quando defeitos palatinos ocasionados por trauma interrompem a separação da cavidade oral e nasal, técnicas cirúrgicas adequadas são essenciais para a reconstrução anatômica. Relata-se um caso de fenda palatina secundária por trauma e fratura de mandíbula, sendo a primeira corrigida cirurgicamente utilizando a técnica de retalho bipediculado deslizante (técnica de Von Langebeck), consistindo no alívio com estafilorrafia e redução da fratura com a técnica de amarria interdental com resina acrílica. As técnicas mostraram-se eficazes no fechamento da fenda palatina e redução da fratura, aliadas aos cuidados adequados no pós-operatório.

Background Long-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia. Methods This retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods. Results Among 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation [SD] 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval [CI] 0.36, 0.41) greater during the 2-year post-index period (0.84 [SD 0.26]) compared with the 2-year pre-index period (0.45 [SD 0.40]). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p

Resumo Este artigo investiga o panorama internacional da implementação do Auxílio Emergencial no contexto da pandemia do Coronavírus. Para tanto, utilizamos: i. a base de dados do Social Protection and Jobs Responses to Covid-19 (Banco Mundial), produzida a partir do levantamento em cinco continentes; ii. os dados provenientes de matérias de jornais ao redor do mundo; e iii. dados dos sites oficiais dos governos locais em diferentes regiões do globo. Em particular no Brasil, encontramos várias adversidades dessa política emergencial: i. as longas filas para cadastramento do benefício, gerando aglomeração; ii. as dificuldades iniciais quanto ao CPF não regularizado; iii. a demora na tomada de decisão para o pagamento do auxílio; iv. a precariedade dos recursos humanos; v. o limitado conhecimento com as tecnologias digitais entre a população mais vulnerável; e vi. os problemas de ineficiências horizontal e vertical. Por fim, este estudo pretende trazer contribuições à relação conflituosa entre Estado e sociedade em tempo de crise sanitária. Abstract This article investigates the international panorama of the implementation of Emergency Income in context of the Coronavirus pandemic. To this, we use: i. the database of Social Protection and Jobs Responses to Covid-19 (World Bank) produced from the survey on five continents; ii. data from newspaper articles around the world; and iii. data from the official websites of local governments in different regions of the globe. Particularly in Brazil, we found several adversities of this emergency policy: i. the long lines for registration of the benefit generating agglomeration; ii. initial difficulties regarding non-regularized CPF; iii. the delay in making the decision to pay the aid; iv. the precariousness of human resources; v. little familiarity with digital technologies among the poorest population; and vi. the problems of horizontal and vertical inefficiency. Lastly, this study aims to bring contributions to the conflictual relation between State and Society in times of health crisis.

Objectives Preferential damage to fast, glycolytic myofibers is common in many muscle-wasting diseases, including Duchenne muscular dystrophy (DMD). Promoting an oxidative phenotype could protect muscles from damage and ameliorate the dystrophic pathology with therapeutic relevance, but developing efficacious strategies requires understanding currently unknown biological roles for dystrophin and utrophin in dystrophic muscle adaptation and plasticity. Methods Combining whole transcriptome RNA sequencing and mitochondrial proteomics with assessments of metabolic and contractile function, we investigated the roles of dystrophin and utrophin in fast-to-slow muscle remodeling with low-frequency electrical stimulation (LFS, 10 Hz, 12 h/d, 7 d/wk, 28 d) in mdx (dystrophin null) and dko (dystrophin/utrophin null) mice, two established preclinical models of DMD. Results Novel biological roles in adaptation were demonstrated by impaired transcriptional activation of estrogen-related receptor alpha-responsive genes supporting oxidative phosphorylation in dystrophic muscles. Further, utrophin expression in dystrophic muscles was required for LFS-induced remodeling of mitochondrial respiratory chain complexes, enhanced fiber respiration, and conferred protection from eccentric contraction-mediated damage. Conclusions These findings reveal novel roles for dystrophin and utrophin during LFS-induced metabolic remodeling of dystrophic muscle and highlight the therapeutic potential of LFS to ameliorate the dystrophic pathology and protect from contraction-induced injury with important implications for DMD and related muscle disorders., Graphical abstract Image 1, Highlights • Transcriptional remodeling to chronic low-frequency electrical stimulation (LFS) is impaired in dystrophic muscles. • Loss of dystrophin and utrophin in dystrophic muscles disrupts remodeling of mitochondrial complexes I-III to chronic LFS. • Loss of dystrophin and utrophin in dystrophic muscles abrogates improvements in fiber respiration after chronic LFS. • Loss of dystrophin and utrophin in dystrophic muscles compromises protection from contraction-induced injury after chronic LFS.

Background: The opioid overdose epidemic in Canada and the United States has become a public health crisis - with exponential increases in opioid-related morbidity and mortality. Recently, there has been an increasing body of evidence focusing on the opioid-sparing effects of medical cannabis use (reduction of opioid use and reliance), and medical cannabis as a potential alternative treatment for chronic pain. The objective of this study is to assess the effect of medical cannabis authorization on opioid use (oral morphine equivalent; OME) between 2013-2018 in Alberta, Canada.Methods: All adult patients defined as chronic opioid users who received medical cannabis authorization in the province of Alberta from 2013-2018 were propensity score matched to non-authorized chronic opioid using controls. 5373 medical cannabis patients were matched to controls, who were all chronic opioid users. The change in the weekly average OME of opioid drugs for medical cannabis patients relative to controls was measured. Interrupted time series (ITS) analyses was used to assess the trend change in OME during the 26 weeks (6 months) before and 52 weeks (1 year) after the authorization of medical cannabis among adult chronic opioid users.Results: Average age was 52 years and 54% were female. Patients on low dose opioids (100), showed a significant decrease over 6 months (-435.5, 95% CI: -596.8 to -274.2) compared to controls. Conclusions: This short-term study found that medical cannabis authorization showed intermediate effects on opioid utilization, which was dependent on initial opioid use. Greater observations of changes in OME appear to be in those patients who were on a high dosage of opioids (OME>100); however, continued surveillance of patients utilizing both opioids and medical cannabis – is warranted by clinicians to understand the long-term potential benefits and any harms of ongoing use.

The former article composes a study about "the woman who killed the fish", published in 1999, by Clarice Lispector and it's pourpouse it's to analyse aspects of the tradtion and inovation on the author's writting, known as one of the most acclaimed writters of the Brazilian modern literature. Known within Brazilian literature for writing books destined to adults, Clarice Lispector began a New style of writing, breaking paterns of traditional and linear writing.&nbsp, O presente artigo constitui um estudo sobre A mulher que matou os peixes, 1999, de Clarice Lispector e seu objetivo é analisar aspectos da inovação na escrita da autora, considerada pela crítica uma das escritoras mais aclamadas da literatura modernista brasileira. Conhecida na tradição da literatura brasileira por ter escritos livros destinados a adultos, Clarice Lispector inaugurou no Brasil um estilo de escrita própria e diferente da sua época por romper com padrões da narrativa linear e tradicional.

BackgroundEbola virus disease (EVD) supportive care strategies are largely guided by retrospective observational research. This study investigated the effect of EVD supportive care algorithms on duration of survival in a controlled nonhuman primate (NHP) model.MethodsFourteen rhesus macaques were challenged intramuscularly with a target dose of Ebola virus (1000 plaque-forming units; Kikwit). NHPs were allocated to intensive care unit (ICU)–like algorithms (n = 7), intravenous fluids plus levofloxacin (n = 2), or a control group (n = 5). The primary outcome measure was duration of survival, and secondary outcomes included changes in clinical laboratory values.ResultsDuration of survival was not significantly different between the pooled ICU-like algorithm and control groups (8.2 vs 6.9 days of survival; hazard ratio; 0.50; P = .25). Norepinephrine was effective in transiently maintaining baseline blood pressure. NHPs treated with ICU-like algorithms had delayed onset of liver and kidney injury.ConclusionsWhile an obvious survival difference was not observed with ICU-like care, clinical observations from this model may aid in EVD supportive care NHP model refinement.

The West Africa Ebola virus disease outbreak of 2014-2016 demonstrated that responses to viral hemorrhagic fever epidemics must go beyond emergency stopgap measures and should incorporate high-quality medical care and clinical research. Optimal patient management is essential to improving outcomes, and it must be implemented regardless of geographical location or patient socioeconomic status. Coupling clinical research with improved care has a significant added benefit: Improved data quality and management can guide the development of more effective supportive care algorithms and can support regulatory approvals of investigational medical countermeasures (MCMs), which can alter the cycle of emergency response to reemerging pathogens. However, executing clinical research during outbreaks of high-consequence pathogens is complicated and comes with ethical and research regulatory challenges. Aggressive care and excellent quality control must be balanced by the requirements of an appropriate infection prevention and control posture for healthcare workers and by overcoming the resource limitations inherent in many outbreak settings. The Joint Mobile Emerging Disease Intervention Clinical Capability was established in 2015 to develop a high-quality clinical trial capability in Uganda to support rigorous evaluation of MCMs targeting high-consequence pathogens like Ebola virus. This capability assembles clinicians, laboratorians, clinical researchers, logisticians, and regulatory professionals trained in infection prevention and control and in good clinical and good clinical laboratory practices. The resulting team is prepared to provide high-quality medical care and clinical research during high-consequence outbreaks.

Objective To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis. Methods We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014-2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis. Results Patients with serologically confirmed chikungunya arthritis (33 of 38 [87%]) were predominantly female (82%) and African Colombian (55%) or white Colombian (33%), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21-23 months). Initial symptoms of chikungunya virus infection included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly. Conclusion This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid.

INTRODUCTION During the 2014-2016 Ebolavirus (EBOV) outbreak, several candidate therapeutics were used in EBOV-infected patients in clinical trials and under expanded access for emergency use. This review will focus briefly on medications used during the outbreak. We will discuss current therapeutic candidates and their status and will then turn to a related and essential topic: supportive care and the standard of care for filovirus infected patients. Potential benefits and pitfalls of combination therapies for filoviruses will be discussed. Areas covered: Clinical trials of therapeutics targeting EBOV; clinical usage of therapeutics during recent EBOV outbreak; potential need for combination therapy; role of supportive care in treatment of Ebola virus disease (EVD). Expert commentary: In the absence of another large scale EBOV outbreak, the path to therapeutic product licensure in the United States of America (USA) would need to be via the FDA Animal Rule. However, human data may be needed to supplement animal data. The future of filovirus therapeutics may therefore benefit by establishing the ability to implement clinical trials in an outbreak setting in a timely fashion. Supportive care guidelines for filovirus infection should be defined and established as standard of care for treatment of EVD.

The establishment of correlates of protection is particularly relevant in the context of rare, highly lethal pathogens. We previously demonstrated that an Ebola glycoprotein virus-like particle (VLP) vaccine, when given as two intramuscular doses, conferred protection from challenge in a murine challenge model. Adjuvants were key to protection and the protection was dependent on a combination of cellular and humoral immunity. In this study, we compared the ability of novel delta inulin-based adjuvant formulations (Advax1-4) to enhance protection mediated by our Ebola VLP vaccine in mice. After two immunizations, Advax-adjuvants that included a TLR9 agonist component induced high IgG responses to the Ebola vaccine, with complete protection against Ebola virus challenge. Although anti-Ebola GP IgG levels waned slowly overtime, protection was durable and was still evident 150 days post-immunization. Mice were protected after just a single VLP immunization with Advax-2 or -4 adjuvants. Advax-adjuvanted VLPs induced a stronger IFN-γ, TNF and IL-12 signature post-immunization. Serum transferred from Advax-adjuvanted vaccinees was able to transfer protection to naïve animals, showing that Ebola protection can be achieved by humoral immunity in the absence of cellular immunity. By contrast, serum from pICLC vaccinees did not transfer protection despite high anti-GP antibody levels on ELISA. These data highlight the importance of adjuvant selection for development of successful Ebola VLP vaccines.

Most alphaviruses are mosquito-borne and can cause severe disease in domesticated animals and humans. The most notable recent outbreak in the Americas was the 2014 chikungunya virus (CHIKV) outbreak affecting millions and producing disease highlighted by rash and arthralgia. Chikungunya virus is a member of the Semliki Forest (SF) serocomplex, and before its arrival in the Americas, two other member of the SF complex, Una (UNAV) and Mayaro (MAYV) viruses, were circulating in Central and South America. This study examined whether antibodies from convalescent CHIKV patients could cross-neutralize UNAV and MAYV. Considerable cross-neutralization of both viruses was observed, suggesting that exposure to CHIKV can produce antibodies that may mitigate infection with UNAV or MAYV. Understanding the impact of CHIKV exposure on population susceptibility to other emerging viruses may help predict outbreaks; moreover, identification of cross-reactive immune responses among alphaviruses may lead to the development of vaccines targeting multiple viruses.

Uma abordagem mais sustentável na produção de concreto autoadensável (CAA) visa substituir os agregados naturais por agregados reciclados, no entanto essa substituição causa uma alteração nas propriedades do material produzido. Esta pesquisa objetiva avaliar o efeito do agregado reciclado miúdo de concreto nas propriedades no estado fresco e endurecido de concretos autoadensáveis, utilizando uma metodologia de dosagem com foco na reologia dos materiais. O estudo de dosagem foi realizado através de uma adequação do método de Gomes utilizando três teores de substituição de AMN por AMRC (10%, 20% e 30%). Foram analisadas as propriedades no estado fresco de acordo com os parâmetros estabelecido na bibliografia sobre o tema e pela prescrição normativa referente, além das propriedades no estado endurecido. Neste estudo, observou-se uma redução da viscosidade aparente, da habilidade passante e da resistência à segregação proporcional ao aumento da substituição de AMN por AMRC. Porém, todos os traços alcançaram a autoadensabilidade exigida, com o mínimo de ajustes. Os traços apresentaram resistência à compressão axial que se enquadravam na classe de concreto estrutural. Portanto, por meio das respostas encontradas durante o estudo de dosagem foi possível produzir concretos autoadensáveis com teores de até 30% de AMRC que atendessem aos requisitos estabelecidos. A more sustainable approach in the production of self-compacting concrete (SCC) aims to replace the natural aggregates by recycled concrete aggregates, however this substitution affects the properties of the concrete produced. This research propose evaluate the effect of the fine recycled aggregate on the properties in the fresh and hardened state of self-compacting concrete using a methodology of dosage focused on the rheology of materials. The dosage study was performed through an adaptation of the Gomes method, and four levels of FNA substitution by FRCA were determined (10%, 20% and 30%). Were analyzed the fresh state properties according to the parameters established according to the specifications on the subject and by the normative prescription of reference, and the properties in the hardened state. In this study, was observed a decrease in apparent viscosity, passing ability and segregation resistance, proportional to the increase in FNA substitution. However, all mix designs have attend the required of self-compacting, with minimum adjustments. All concretes obtained axial compressive strength at which fit in the structural concrete class. Therefore, through the responses founded during the dosing study, it was possible to produce self-compacting concretes with 30% of FRCA that met the requirements established.

Objetivo: Discorrer sobre seus impactos clínicos e de comorbidades associadas, abordando também, medidas terapêuticas e suas eficácias. Revisão bibliográfica: A SHO é uma condição crônica dada pela associação de fatores como hipercapnia, alterações respiratórias e obesidade. Juntamente a SHO podem surgir outros distúrbios, como AOS e alterações cardiovasculares, as quais se correlacionam com desfechos desfavoráveis. O tratamento de escolha inicial da SHO é o CPAP, sendo indispensável uma abordagem multidisciplinar sobre a melhora da higiene do sono e mudanças de estilo de vida, medidas essas, consideradas primordiais. Considerações finais: Por meio de uma análise sem sistematização e comparação com outras técnicas disponíveis, constatou-se que o tratamento de escolha é feito com o CPAP, devido a redução do Índice de Apneia-Hipopneia (IAH) na maioria dos pacientes, não sendo necessária a associação com outras medidas terapêuticas. Terapias como a traqueostomia e flebotomia devem ser realizadas somente se necessário. Além disso, devem ser evitadas medicações como medroxiprogesterona e acetazolamida e o uso excessivo de diuréticos de alça e sedativos/hipnóticos.

Despite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk–pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid–based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp). We review Ebola therapeutics progress in the aftermath of the West Africa Ebola virus outbreak and attempt to offer a glimpse of a path forward.

Objective The insulin-like growth factor binding proteins (IGFBPs) are thought to modulate cell size and homeostasis via IGF-I-dependent and -independent pathways. There is a considerable dearth of information regarding the function of IGFBPs in skeletal muscle, particularly their role in the pathophysiology of Duchenne muscular dystrophy (DMD). In this study we tested the hypothesis that intramuscular IGFBP-2 overexpression would ameliorate the pathology in mdx dystrophic mice. Design 4week old male C57Bl/10 and mdx mice received a single intramuscular injection of AAV6-empty or AAV6-IGFBP-2 vector into the tibialis anterior muscle. At 8weeks post-injection the effect of IGFBP-2 overexpression on the structure and function of the injected muscle was assessed. Results AAV6-mediated IGFBP-2 overexpression in the tibialis anterior (TA) muscles of 4-week-old C57BL/10 and mdx mice reduced the mass of injected muscle after 8weeks, inducing a slower muscle phenotype in C57BL/10 but not mdx mice. Analysis of inflammatory and fibrotic gene expression revealed no changes between control and IGFBP-2 injected muscles in dystrophic ( mdx ) mice. Conclusions Together these results indicate that the IGFBP-2-induced promotion of a slower muscle phenotype is impaired in muscles of dystrophin-deficient mdx mice, which contributes to the inability of IGFBP-2 to ameliorate the dystrophic pathology. The findings implicate the dystrophin-glycoprotein complex (DGC) in the signaling required for this adaptation.

Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials.

The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. The Ebola virus-like particle (VLP) vaccine expressing Ebola virus glycoprotein (GP) and matrix protein (VP40) was used in this study to evaluate the ability of TLR4 agonist glucopyranosyl lipid adjuvant (GLA) formulated in a stable emulsion (SE) to enhance immunogenicity and promote durable protection against mouse-adapted Ebola virus (ma-EBOV). Antibody responses and Ebola-specific T cell responses were evaluated post vaccination. Survival analysis after lethal ma-EBOV challenge was performed 4 weeks and 22 weeks following final vaccination. GLA-SE enhanced EBOV-specific immunity and resulted in long-term protection against challenge with ma-EBOV infection in a mouse model. Specifically, GLA-SE elicited Th1-skewed antibodies and promoted the generation of EBOV GP-specific polyfunctional T cells. These results provide further support for the utility of TLR4 activating GLA-SE-adjuvanted vaccines.