investments to support countries with greatest burden of viral hepatitis All heavily burdened countries to have fully funded elimination plans by 2019 Recognition of need to focus on high burden countries and support for national policy development (All) Funding for national elimination plans Creation of fiscal space for new programmes with costed investment programmes Adopt domestic innovative finance tools where appropriate Support national policy makers in their activity (WHO, UNITAID, NGOs) Provide international support for financing measures (UNITAID, GFATM, bilaterial donors) Prevention Ensure all WHO elimination targets addressed in plans Address operational challenges in delivery of birth dose HBV vaccine Ensure provision of harm reduction services and engage with marginalised group (e.g. prisoners, PWIDs). Ensure clear public health messages to encourage testing and treatment Support countries to decriminalise injecting drug use and ensure equitable access to services for all (NGOs, WHO, civil society) Ensure appropriate funding for HBV vaccine, including birth dose (GAVI, WHO) Support R&D into HCV vaccine development (Research funders and pharma) Testing and Models of Care Focus on substantially scaling up testing for HBV and HCV Create and evaluate simplified care pathways relevant to local setting, integrating with existing services. Promote task sharing and decentralisation of care through capacity building, training and removal of Support operational research into simplified pathways (Research funders, UNITAID) requirements for specialised prescribing Diagnostics Ensure testing is integrated into the wider healthcare system, rather than centralised facilties Ensure access to quality diagnostics through Essential Diagnostic List and prequalification (WHO, funders) Support implementation science for models of care and R&D into novel diagnostics suitable for decentralised settings. (Research funders, FIND, industry) Access to treatment Ensure all Essential Medicines for viral hepatitis are included in national programmes, with an emphasis on pan-genotypic regimens Apply comprehensive policy approach to promoting access, including compulsory licensing Ensure all essential medicines are pre-qualified and either available through voluntary licensing or Medicines Patent Pool (WHO, NGOs, civil society, funders) Support shared procurement mechanisms for treatment (PAHO) Monitor Progress National plans need clearly defined, measurable objectives Develop new indices of national progress Progress of individual countries needs to be closely monitored towards elimination goals (Polaris, WHO, Creation of Elimination Index) Develop greater capacity for advocacy in high burden regions (all) Viral hepatitis is one of the leading causes of death in the world. 96% of those deaths are due to hepatitis B and C, which are the focus of this commission. Unlike many other major diseases, the tools exist to eliminate viral hepatitis. A highly effective vaccine is available to prevent hepatitis B, and a revolution in HCV treat...

Three-finger fold toxins are miniproteins frequently found in Elapidae snake venoms. This fold is characterized by three distinct loops rich in b-strands and emerging from a dense, globular core reticulated by four highly conserved disulfide bridges. The number and diversity of receptors, channels, and enzymes identified as targets of three-finger fold toxins is increasing continuously. Such manifold diversity highlights the specific adaptability of this fold for generating pleiotropic functions. Although this toxin superfamily disturbs many biological functions by interacting with a large diversity of molecular targets, the most significant target is the cholinergic system. By blocking the activity of the nicotinic and muscarinic acetylcholine receptors or by inhibiting the enzyme acetylcholinesterase, three-finger fold toxins interfere most drastically with neuromuscular junction functioning. Several of these toxins have become powerful pharmacological tools for studying the function and structure of their molecular targets. Most importantly, since dysfunction of these receptors/enzyme is involved in many diseases, exploiting the three-finger scaffold to create novel, highly specific therapeutic agents may represent a major future endeavor.

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with openlabel eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population.

Objective To assess whether eculizumab, a terminal complement inhibitor, improves patient‐ and physician‐reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods Patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open‐label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open‐label extension were analyzed. Results Of the 125 patients who participated in REGAIN, 117 enrolled in the open‐label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open‐label extension. Interpretation Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis.

ResumoAs fissuras são problemas que surgem frequentemente nas estruturas de concreto, que podem chegar a afetar sua durabilidade com redução de vida útil. No entanto, a identificação destas patologias é ainda limitada à inspeção visual, sem considerar outras tecnologias. O objetivo deste estudo consiste em verificar a aplicabilidade da termografia infravermelha para a detecção e análise de fissuras verticais de diferentes profundidades (5, 10 e 15) cm. Para tanto, foram moldados três corpos de prova de dimensões (50x20x20) cm, com fissuras criadas artificialmente utilizando placas de alumínio. Os corpos de prova foram expostos à radiação solar e às condições ambientais, sendo monitoradas durante 12 horas, das 7 às 19 horas. Os resultados apontaram que as fissuras têm uma temperatura mais baixa que o concreto intacto durante o dia, e apresentam um comportamento inverso durante a noite. Além disso, observou-se que quanto mais profunda é uma fissura, mais fria se torna em relação às fissuras superficiais. A termografia infravermelha demonstra capacidade de identificar fissuras durante a maior parte do dia e também permite uma análise das suas características através do gradiente térmico, formado entre a temperatura da fissura e o concreto. No entanto, é uma técnica sensível às condições ambientais, por conseguinte, a sua aplicação é sujeita a parâmetros ambientais ideais.Palavras-Chave: Termografia infravermelha; Fissuras; Concreto. AbstractCracks are problems that often arise in concrete structures, which can affect their durability with reduced life. However, the identification of these pathologies is still limited to visual inspection,

Sesamoiditis secondary to gout is an extremely rare condition with few case reports in the literature. It is an important differential diagnosis because the treatment depends on targeted therapy, unlike the main causes of sesamoiditis that often involves immobilization with special orthoses and prescription of anti-inflammatory drugs. We report here a case of a 38-year-old male, athlete, with bipartite medial sesamoid, who had insidious pain in the base of the left hallux. Laboratory tests showed no alterations, and imaging examinations demonstrated sesamoiditis with suspicion of stress fracture. The patient was initially prescribed an immobilization boot and analgesic and anti-inflammatory drugs, but he did not respond to the measures taken. After the onset of the same condition in the contralateral foot and getting the same imaging findings, we began an investigation of systemic disease, focusing on gout, because of a positive family history, which was confirmed by dual-energy computed tomography.

OBJETIVO: Investigar o desempenho de escolares de 7 a 12 anos de idade, sem queixas auditivas, no teste Gaps-in-Noise (GIN). MÉTODOS: Todas as crianças foram submetidas à otoscopia, audiometria tonal, logoaudiometria, medidas de imitância acústica e teste dicótico de dígitos. Somente realizaram o teste GIN os escolares com resultados dentro do esperado nos referidos testes (37 crianças, sendo 20 de escola particular e 17 de escola pública). Uma vez que não houve diferença entre o desempenho das crianças de escola pública e escola particular, o grupo foi tratado como único. RESULTADOS: Foram encontrados os seguintes valores médios no GIN por faixa etária: 7 anos (5,65 ms); 8 anos (5,12 ms); 9 anos (4,87 ms); 10 anos (5,1 ms) e acima de 11 anos (4,75 ms). CONCLUSÃO: O limiar médio de detecção de gap na orelha direita foi de 5 ms e na orelha esquerda foi de 5,19 ms. Não houve diferença entre as diversas faixas-etárias, orelhas e gêneros, no que se refere aos limiares de detecção de gap avaliados pelo GIN.

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