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Current inhibitors of platelet integrin αIIbβ3 cause excessive bleeding, which limited their clinical use in cardiac patients. Here the authors design pure orthosteric αIIbβ3 inhibitors that prevent platelet aggregation and thrombosis without causing bleeding in humanized mouse models of thrombosis

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu’s arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZ MONO ) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZ COMBO ) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5–50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0–31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5–50.0) to 5.0 (0.0–5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0–14.0) months. Twenty-three (42.6%) patients were on TCZ MONO and 31 (57.4%) on TCZ COMBO : MTX ( n = 28), cyclosporine A ( n = 2), azathioprine ( n = 1). Patients on TCZ COMBO were younger [38.0 (27.0–46.0) versus 45.0 (38.0–57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0–38.0) versus 6.0 (1.0–23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7–5.6) versus 1.3 (0.3–3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.

We used high-resolution rotational spectroscopy coupled to a laser ablation source to study the conformational panorama of perillartine, a solid synthetic sweetener. Four conformers were identified under the isolation conditions of the supersonic expansion, showing that all of them present an E configuration of the C=N group with respect to the double bond of the ring. The observed structures were verified against Shallenberger–Acree–Kier’s sweetness theory to shed light on the structure–sweetness relationship for this particular oxime, highlighting a deluge of possibilities to bind the receptor.

La idea de clasificación es bien conocida por quienes se dedican a la documentación. Sin entrar en disquisiciones formales, se trata de organizar los documentos en alguna forma que permita después su mejor recuperación. En torno a ello se han elaborado diversas técnicas, que se han aplicado con mejor o peor fortuna. Con la creciente disponibilidad de documentos en formato electrónico, susceptibles, por consiguiente, de ser procesados de manera automática, surge la posibilidad de abordar la clasificación de documentos de manera automática. Este trabajo describe algunas de las técnicas y algoritmos aplicables en clasificación automática, los conceptos básicos en que se basan tales algoritmos, así como los instrumentos necesarios para aplicarlos. Del mismo modo, en la medida en que tales técnicas y algoritmos hayan sido aplicados, se ofrece una estimación del alcance y posibilidades de cada uno de ellos.

Acute kidney injury can progress to chronic kidney disease. Here Dehnadiet al. develop a post-ischaemic chronic kidney disease model in cynomolgus monkeys and show that prophylactic inhibition of CD11b/CD18 leukocyte receptor via a monoclonal antibody inhibits progression of kidney disease and fibrosis.

Sugar beet pulp (SBP) and lemon peel wastes (LPW) were used to obtain two mixtures of pectic oligosaccharides (denoted as SBPOS and LPOS, respectively). Oligogalacturonides in LPOS showed a larger molecular weight, higher degree of methylation and lower degree of acetylation than the ones in SBPOS. The suitability of pectic oligosaccharides, pectins from SBP and LPW and commercial FOS for causing prebiotic effects were compared by in vitro fermentation and fluorescence in situ hybridization using human faecal inocula and eight different probes. The joint populations of bifidobacteria and lactobacilli increased from 19% up to 29%, 34% and 32% in cultures with LPOS, SBPOS and FOS, respectively. Faecalibacterium and Roseburia also increased their counts with all the substrates (especially with LPOS). The highest concentrations of organic acids were observed in media containing oligosaccharides. This work confirms that pectic oligosaccharides present better prebiotic properties than pectins, and similar or better than FOS.

Once applied, an herbicide first makes contact with leaves and soil. It is known that photolysis can be one of the most important processes of dissipation of herbicides in the field. However, degradation does not guarantee detoxification and can give rise to byproducts that could be more toxic and/or persistent than the active substance. In this work, the photodegradation of alloxydim herbicide in soil and leaf cuticle surrogates was studied and a detailed study on the phytotoxicity of the main byproduct on sugar beet, tomato, and rotational crops was performed. Quantitative structure–activity relationship (QSAR) models were used to obtain a first approximation of the possible ecotoxicological and environmental implications of the alloxydim and its degradation product. The results show that alloxydim is rapidly degraded on carnauba and sandy loam soil surfaces, two difficult matrices to analyze and not previously studied with alloxydim. Two transformation products that formed in both matrices were identified: alloxydim Z-isomer and imine derivative (mixture of two tautomers). The phytotoxicity of alloxydim and the major byproduct shows that tomato possesses high sensitivity to the imine byproduct, while wheat crops are inhibited by the parent compound. This paper demonstrates the need to further investigate the behavior of herbicide degradation products on target and nontarget species to determine the adequate use of herbicidal products to maximize productivity in the context of sustainable agriculture.

Lesões do nervo espinhal são incomuns e na maioria das vezes iatrogênicas. São mais usualmente encontradas após procedimentos cirúrgicos no triângulo cervical posterior, principalmente biópsias de linfonodos. Apresentamos sete casos de neuropatia do nervo espinhal secundária a cirurgias, estudados mediante eletromiografia (EMG) quantitativa e exames eletrofisiológicos complementares. Em todos os pacientes estava afetado o feixe superior do trapézio, com ombro caído ou limitação para elevação do braço. Dor e queixas sensitivas estavam presentes em quase todos os pacientes e muito provavelmente decorriam de lesão associada dos ramos cutâneos do plexo cervical. O padrão de lesão correpondeu àquele da axonotmese, mas alguns pacientes exibiam sinais de compressão por tecido cicatricial. Salientamos a necessidade de exploração cirúrgica e reparo do nervo nos casos com recuperação lenta.

Depois de observar há vários anos que o registro eletromiográfico (BMG) do fenômeno de Strümpell (FS) é útil para diagnosticar síndromes piramidais, a partir de março-1987, o autor passou a pesquisar o FS sistematicamente durante a EMG dos músculos tibials anteriores. Realiza esse registro com eletrodo concêntrico de agulha e calibração de 0,05 a 0,2mV e 1s por divisão. Ao paciente, em decúbito dorsal, é solicitado realizar extensão vagarosa e completa da coxa. O FS positivo caracteriza-se por EMG de contração tônica involuntária, de amplitude crescente, do músculo tibial anterior, simultaneamente à extensão da coxa. Com a finalidade de sistematizar a EMG dessa sincinesia e de avaliar sua utilidade no diagnóstico da síndrome piramidal, o autor revisou os 579 relatórios de EMG realizados a partir de março-1987. Foram encontrados 26 (4,49%) relatórios de pacientes com FS positivo, que serviu para estabelecer ou confirmar que esses pacientes apresentavam síndromes piramidais. Em 20 pessoas de idade parecida e sem sinais de liberação piramidal, a pesquisa do FS se acompanhava de silêncio eletromiográfico (90%) ou de algumas contrações clônicas (10%) do tibial anterior. O autor recomenda a inclusão da pesquisa de FS no exame EMG convencional dos tibials anteriores, especialmente em casos de esclerose lateral amiotrófica e frente a síndromes mielorradiculares ou medulares.

São apresentados os resultados dos exames clínicos, eletrofisiológicos e do estudo do ponto motor, da imunofluorescência, da histoquímica e da ultrami-croscopia da biópsia muscular de um caso de miopatia miotubular. São discutidos estes resultados em relação aos achados de 56 casos desta moléstia consignados na literatura até 1978, sendo dada enfase à etiopatogenia.

Estudamos um paciente com quadro clínico rebelde, produzido por intoxicação pelo Parathion. Foi observado um fenômeno miotônico transitório, não descrito na literatura revisada. A constatação de cifras de AchE eritrocitária baixas e de colinesterase plasmática normais, indicou que era portador de déficit congênito de AchE, esclarecendo-se a evolução crônica do seu quadro. O fenômeno miotônico associado ao quadro clínico, eletrofisiológico, histológico e bioquímico fazem deste paciente um modelo clínico, de etiologia conhecida, da discutida síndrome de Isaacs.

Quatro irmãos com moléstias de Charcot-Marie-Tooth são estudados do ponto de vista clínico e genético. São ressaltadas, mediante análise da sintomatologia, as formas de transição no grande grupo de moléstias heredodegenerativas, sendo atribuída particular ênfase às formas entre a moléstia de Charcot-Marie-Tooth e a de Friedreich. Nos casos apresentados havia sinais clínicos da amiotrofia de Charcot-Marie-Tooth e da degeneração espinocerebelar de Friedreich. No estudo genético foram observadas aberrações cromossômicas, fenômeno inédito na moléstia de Charcot-Marie-Tooth.Four brothers with Charcot-Marie-Tooth disease are studied clinically and genetically. By comparing the symptomatology, the mixed clinical forms within the great group of heredodegenerative diseases are enfazised, with special attention to the intermediate forms between Charcot-MarieTooth and Friedreich diseases. In the present cases there were signs of Charcot-Marie-Tooth's peroneal muscular atrophy and Friedreich's spinocerebelar degeneration. By the genetic study a cromosomal breakage, an unusual phenomenon in Charcot-Marie-Tooth disease, was observed.

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.

Nicotine has been investigated in the gas phase and two conformational forms were characterized through their rotational spectra. Two spectroscopic techniques have been used to obtain the spectra: a new design of broadband Fourier transform microwave (FTMW) spectroscopy with an in-phase/quadrature-phase-modulation passage-acquired-coherence technique (IMPACT) and narrowband FTMW spectroscopy with coaxially oriented beam-resonator arrangement (COBRA). The rotational, centrifugal distortion and hyperfine quadrupole coupling constants of two conformers of nicotine have been determined and found to be in N-methyl transconfigurations with the pyridine and pyrrolidine rings perpendicular to one another. The quadrupole hyperfine structure originated by two 14N nuclei has been completely resolved for both conformers and used for their unambiguous identification. [ABSTRACT FROM AUTHOR]

Rotational spectroscopy in combination with molecular beams and laser ablation (laser-ablation molecular-beam Fourier transform microwave (LA-MB-FTMW) spectroscopy) has proved to be successful in characterizing the conformers of natural amino acids. The procedure usually followed to assign and identify the different conformers of an amino acid from the rotational spectrum is described through the study of the natural amino acid l-threonine. The solid sample of l-threonine was vaporized by laser pulses, diluted in Ne and supersonically expanded between the mirrors of a Fabry–Pérot resonator where it was spectroscopically probed by microwave radiation. The rotational and nuclear quadrupole coupling constants extracted from the analysis of the rotational spectrum are directly compared with those predicted by ab initiomethods to achieve the conclusive identification of seven different conformers. A complex hydrogen bonding network arises as a consequence of the polar side chain of threonine. [ABSTRACT FROM AUTHOR]

The objective of this communication is to make a review of the evolution, in the last 10 years, in the field of the Web information retrieval. With the implantation of the different cybermetrics techniques the evolution from the studies of the Web has been spectacular and is at the moment an inexhaustible field of study. [ABSTRACT FROM AUTHOR]