Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Endoscopic Anatomy of the Pterygopalatine Fossa and the Transpterygoid Approach: Development of a Surgical Instruction Model

Introduction: The pterygopalatine fossa (PPF) is a narrow space located between the posterior wall of the antrum and the pterygoid plates. Surgical access to the PPF is difficult because of its protected position and its complex neurovascular anatomy. Endonasal approaches using rod lens endoscopes, however, provide better visualization of this area and are associated with less morbidity than external approaches. Our aim was to develop a simple anatomical model using cadaveric specimens injected with intravascular colored silicone to demonstrate the endoscopic anatomy of the PPF. This model could be used for surgical instruction of the transpterygoid approach. Methods: We dissected six PPF in three cadaveric specimens prepared with intravascular injection of colored material using two different injection techniques. An endoscopic endonasal approach, including a wide nasoantral window and removal of the posterior antrum wall, provided access to the PPF. Results: We produced our best anatomical model injecting colored silicone via the common carotid artery. We found that, using an endoscopic approach, a retrograde dissection of the sphenopalatine artery helped to identify the internal maxillary artery (IMA) and its branches. Neural structures were identified deeper to the vascular elements. Notable anatomical landmarks for the endoscopic surgeon are the vidian nerve and its canal that leads to the petrous portion of the internal carotid artery (ICA), and the foramen rotundum, and V2 that leads to Meckel`s cave in the middle cranial fossa. These two nerves, vidian and V2, are separated by a pyramidal shaped bone and its apex marks the ICA. Conclusion: Our anatomical model provides the means to learn the endoscopic anatomy of the PPF and may be used for the simulation of surgical techniques. An endoscopic endonasal approach provides adequate exposure to all anatomical structures within the PPF. These structures may be used as landmarks to identify and control deeper neurovascular structures. The significance is that an anatomical model facilitates learning the surgical anatomy and the acquisition of surgical skills. A dissection superficial to the vascular structures preserves the neural elements. These nerves and their bony foramina, such as the vidian nerve and V2, are critical anatomical landmarks to identify and control the ICA at the skull base

Crescimento de plantas micropropagadas de macieira em casa de vegetação com aplicações de ácido giberélico Growth of micropropagated apple plants in greenhouse with gibberellic acid applications

O objetivo deste trabalho foi otimizar o crescimento de plantas micropropagadas do porta-enxerto de macieira 'Marubakaido' (Malus prunifolia) em casa de vegetação, por meio da aplicação de ácido giberélico (AG3) por uma, duas, ou três vezes, em intervalos semanais. As concentrações testadas foram: 0, 50, 100, 200, 400, 800 e 1.600 mg L-1. O crescimento das plantas foi avaliado quinzenalmente, por um período de dois meses. O comprimento dos entrenós e a matéria seca da parte aérea das plantas também foram avaliados no final do experimento. Três aplicações de AG3 na concentração de 800 mg L-1 foi o tratamento que proporcionou a maior taxa de crescimento das plantas (912% contra 114% das plantas não-tratadas), além de proporcionar plantas com maior comprimento de entrenós e massa seca da parte aérea. Plantas pulverizadas uma única vez não apresentaram diferenças significativas em nenhuma das variáveis estudadas. Estes resultados sugerem que o uso do AG3 em plantas de macieira, oriundas da micropropagação, melhora o crescimento, embora um número de pelo menos três aplicações, associado com concentrações mais elevadas, seja necessário para melhorar a eficiência deste regulador.<br>Aiming to optimize plant growth of the apple rootstock cultivar Marubakaido (Malus prunifolia) in greenhouse, one-year old plants coming from in vitro cultivation were sprayed once, twice and three times in a 7-day interval with gibberellic acid (GA3). The concentrations of 0, 50, 100, 200, 400, 800 and 1,600 mg L-1 were used. Plant growth was evaluated every two weeks during two months. Internode length, number of buds and the dry mass of the aerial part were also evaluated at the end of the experiment. Three sprays of GA3 at 800 mg L-1 was the best treatment providing the largest rate of plant growth (912% against 114% of non-treated plants) in relation to their initial height, besides providing larger internode length and higher dry matter of aerial parts. Plants sprayed once did not present significant response to GA3 for none of the studied variables. These results suggest that the use of GA3, in apple plants coming from micropropagation, improves the growth, although a number of at least three applications, associated with high concentrations, is necessary to improve the efficiency of this regulator

Superação de dormência em sementes de Gleditschia amorphoides Taub. Overcoming of seed dormancy in Gleditschia amorphoides Taub.

O trabalho teve como objetivo avaliar métodos para a superação da dormência de sementes de sucará. As sementes receberam os seguintes tratamentos: 1) testemunha; 2) escarificação mecânica; 3) escarificação mecânica + água/24h; 4) escarificação mecânica + água quente/24h; 5) água quente/24h; 6) ácido sulfúrico (H2SO4)/1h; 7) H2SO4/2h; 8) H2SO4/1h + água/24h; 9) H2SO4/30min + água corrente/4h; 10) escarificação mecânica + água corrente/4h. O teste de germinação foi conduzido em rolos de papel Germitest acondicionados em câmara de germinação, à 25&deg;C, com fotoperíodo de 12h por 26 dias. Avaliou-se também o tempo e a velocidade média de germinação. O delineamento experimental foi inteiramente casualizado, com quatro repetições de 25 sementes. O melhor desempenho germinativo foi registrado para as sementes submetidas à escarificação mecânica e química, com médias entre 76 e 98% de germinação, respectivamente, 2,17 a 2,88 dias para tempo médio de germinação e 0,46 a 0,47 sementes/dia para velocidade média de germinação, demonstrando serem estes os melhores métodos para superação da dormência de sementes dessa espécie.<br>The objective of this research was to evaluate methods to overcome dormancy of seeds of Gleditschia amorphoides. For dormancy's overcoming the seeds received the following treatments: 1) control; 2) mechanical scarfication 3) mechanical scarfication + water/24h; 4) mechanical scarfication + hot water/24h; 5) hot water/24h; 6) sulfuric acid (H2SO4)/1h; 7) H2SO4/2h; 8) H2SO4/1h + water/24h; 9) H2SO4/30min + flowing water/4h; 10) mechanical scarfication + flowing water/4h. Germination was done in rolls of Germitest conditioned in a germination chamber under 25&deg;C, during 12h for 26 days. Percentage, time and average speed of germination were evaluated. The experimental design was completely casual with 10 treatments, 4 repetitions and 25 seeds. The best results were recorded for treatments with mechanical and chemical scarification with averages between 76 and 98% of germination, from 2.17 to 2.88 days for medium time for germination and 0.46 to 0.48 seeds/day for average speed of germination, demonstrating that these are the best methods to overcome dormancy of seeds

Acclimatization of 'VR043-43' (Vitis vinifera x Vitis rotundifolia) grapevine rootstock Aclimatização do porta-enxerto de videira 'VR043-43' (Vitis vinifera x Vitis rotundifolia)

The pre-acclimatization stage can be used to improve micropropagation protocols and increase the yield of produced plants. The influence of sucrose and photon flux density (PFD) levels on the acclimatization of in vitro-grown 'VR043-43' (Vitis vinifera x Vitis rotundifolia) grapevine rootstocks was evaluated. Rooted shoots were obtained from 4-week-old in vitro shoots cultivated in QL (Quoirin and Lepoivre, 1977) culture medium supplemented with 15, 30 and 45 g L-1 of sucrose. The experiment was kept in a 25 ± 2ºC growth room, under 16-h photoperiod and PFD of 18 µmol m-2 s-1 or 43 µmol m-2 s-1. Plants were transferred to an intermittent misting system greenhouse for 10 d followed by 20 d of once-a-day watering routine using a handheld hose. Plant height was influenced by sucrose concentration, and shoots produced on media supplemented with 30 g L-1 sucrose were the tallest (5.0 cm). The largest leaf area was obtained with 31.3 g L-1 of sucrose, under the PFD of 43 µmol m-2 s-1 (13.3 cm²). Absence of sucrose in the culture medium led to a significant reduction in leaf area at both PFDs. Shoot (aerial part) dry matter was largest when 30 or 45 g L-1 of sucrose (17.5 and 16.7 mg per plant, respectively) were used. Microcuttings rooted in all sucrose concentrations tested. The highest survival percentage (100%) during ex vitro acclimatization was obtained for shoots cultured in media supplemented with 45 g L-1 of sucrose under both PFDs tested.<br>A fase de pré-aclimatização pode ser utilizada para aperfeiçoar os protocolos de micropropagação e aumentar o rendimento na produção de mudas. Avaliou-se a influência da sacarose e níveis de densidade de fluxo de fóton (DFF) in vitro, na sobrevivência das mudas do porta-enxerto de videira 'VR043-43'(Vitis vinifera x Vitis rotundifolia), na fase de aclimatização. Microestacas obtidas de brotações in vitro foram cultivadas em meio de cultura QL suplementado 15, 30 e 45 g L-1 de sacarose. O experimento foi mantido em sala climatizada com temperatura de 25 ± 2ºC, fotoperíodo de 16 horas e DFF de 18 µmol m-2 s-1 ou 43 µmol m-2 s-1. As plantas foram transferidas para uma câmara de nebulização intermitente por 10 d e mantidas durante 20 d em casa de vegetação com irrigação manual. A altura das plantas foi influenciada pelas concentrações de sacarose, sendo a maior altura (5,0 cm) obtida com a concentração de 30 g L-1 de sacarose. A maior área foliar foi obtida com 31,3 g L-1 de sacarose na DFF de µmol m-2 s-1 (13,3 cm²). A ausência de sacarose no meio de cultura promoveu redução significativa na área foliar nas duas DFFs testadas. A matéria seca da parte aérea foi maior quando o meio de cultura foi suplementado com 30 ou 45 g L-1 de sacarose (17,5 e 16,7 mg por planta, respectivamente). Houve enraizamento das microestacas em todas as concentrações de sacarose testadas. Alta porcentagem de sobrevivência (100%) durante a aclimatização ex vitro foi obtida quando as brotações foram cultivadas no meio de cultura suplementado com 45 g L-1 de sacarose em ambas DFFs testadas

Micropropagação de Cabralea canjerana Micropropagation of Cabralea canjerana

A Cabralea canjerana (Vell.) Mart. (Meliaceae) (canjarana) é uma espécie arbórea nativa brasileira importante para fornecimento de madeira de boa qualidade. As sementes desta espécie não podem ser armazenadas por muito tempo e, por tanto, existe a necessidade do desenvolvimento de técnicas alternativas de propagação como a micropropagação. Neste trabalho, foram realizados experimentos de multiplicação utilizando segmentos nodais, retirados de plantas germinadas in vitro. Os segmentos foram inoculados em meio de cultura MS ou WPM, adicionado de 6-benzilaminopurina (BAP) e, ou, 2-isopenteniladenina (2-iP) nas concentrações de 2,5 ou 5 &micro;M. Microestacas de rebrotas foram colocadas em meio de cultura MS/2, com a metade da concentração dos sais do meio MS, adicionado de ácido indol 3-butírico (AIB) (0, 2,5 e 5 &micro;M). Após sete dias, foram transferidas para meio MS/2 sem auxina e na luz. Na fase de multiplicação, o meio de cultura MS foi mais adequado que o meio WPM. O segmento nodal, em presença de 2,5 &micro;M de BAP, propiciou um dos melhores resultados, com uma taxa de multiplicação de 1,77 por mês, em meio de cultura MS. O enraizamento das microestacas oriundas de rebrotas foi de 87,5% em presença de 5 &micro;M de AIB durante sete dias. A aclimatização foi realizada em casa de vegetação e proporcionou 90% de sobrevivência das mudas após 30 dias. A micropropagação da canjarana a partir de segmentos nodais de mudas cultivadas in vitro é viável para a multiplicação dessa espécie.<br>Cabralea canjerana (Vell.) Mart. (Meliaceae) ("canjarana") is a native tree of economic importance in Brazil. The storage of seeds is of short duration and it is therefore necessary to establish a protocol for micropropagation of this species. In this work, multiplication experiments were carried out using nodal segments, excised from in vitro germinated plants. The segments were inoculated in MS or WPM culture medium, supplemented with 6-benzylaminopurine (BAP) and/or 2-isopentenyladenine (2-iP) at 2.5 or 5 &micro;M. Micro-cuttings were taken from new shoots developed from the seeds and used in a rooting experiment using a culture medium with half-strength MS medium (MS/2) supplemented with indolbutyric acid (IBA) (0, 2.5 and 5 &micro;M). After 7 days in this medium, they were transferred to MS/2 medium without auxin under light. During the multiplication phase, the MS culture medium was more suitable for the multiplication of C. canjerana than WPM medium. The nodal segments cultured in the presence of 2.5 &micro;M BAP showed the best result, with a multiplication rate of 1.77 per month on MS medium. The rooting of the microcuttings was 87.5% when they were kept in the presence of 5 &micro;M IBA for 7 days. An acclimatization rate of 90% was achieved after 30 days in the greenhouse. In conclusion, the micropropagation of C. canjerana from nodal segments of plantlets is possible for this species