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Subcutaneous (SC) injection of protein-based therapeutics is a convenient and clinically established drug delivery method. However, progress is needed to increase the bioavailability. Transport of low molecular weight (Mw) biotherapeutics such as insulin and small molecule contrast agents such as lipiodol has been studied using X-ray computed tomography (CT). This analysis, however, does not translate to the investigation of higher Mwtherapeutics, such as monoclonal antibodies (mAbs), due to differences in molecular and formulation properties. In this study, an iodinated fluorescein analog rose bengal (RB) was used as a radiopaque and fluorescent label to track the distribution of bovine serum albumin (BSA) compared against unconjugated RB and sodium iodide (NaI) via CT and confocal microscopy following injection into ex vivo porcine SC tissue. Importantly, the high concentration BSA-RB exhibited viscosities more like that of viscous biologics than the small molecule contrast agents, suggesting that the labeled protein may serve as a more suitable formulation for the investigation of injection plumes. Three-dimensional (3D) renderings of the injection plumes showed that the BSA-RB distribution was markedly different from unconjugated RB and NaI, indicating the need for direct visualization of large protein therapeutics using conjugated tags rather than using small molecule tracers. Whereas this proof-of-concept study shows the novel use of RB as a label for tracking BSA distribution, our experimental approach may be applied to high Mwbiologics, including mAbs. These studies could provide crucial information about diffusion in SC tissue and the influence of injection parameters on distribution, transport, and downstream bioavailability.

Among the forage species cultivated in South America, the genus Urochloa is the most used, and the cultivar Marandu of U. brizantha is the most widely planted in Brazil. The objective of this study was to evaluate forage performance in association with Azospirillum brasilense, combined with nitrogen (N) fertilisation. The study was conducted under field conditions in Araguaína, Tocantins, in the central region of Brazil, between March 2016 and March 2017. Four N fertiliser rates (0, 12.5, 25 and 50kg/ha of N per cutting cycle) were combined with two inoculation treatments (inoculated and non-inoculated), with evaluations carried out in three periods of the year (transition, dry and wet seasons). Marandu grass plants inoculated with A. brasilense had greater plant height, number of tillers and forage production than non-inoculated plants, regardless of the N rate. Inoculation with A. brasilense allowed a 20% reduction in N fertilisation. Our results indicate that inoculation with A. brasilense in Marandu grass, as well as increasing forage production, can help to mitigate the stresses caused by the dry season.

The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, meningoencephalitis, and Guillain-Barré syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase–polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections.

Obstructive sleep apnea is frequent during the acute phase of stroke, and it is associated with poorer outcomes. A well-established relationship between supine sleep and obstructive sleep apnea severity exists in non-stroke patients. This study investigated the frequency of supine sleep and positional obstructive sleep apnea in patients with ischemic or hemorrhagic stroke.

Background.Oxygen free radicals are considered to be important components involved in the physiopathological tissue alterations observed during ischemia and reperfusion. The objective of the present study was to investigate oxidative stress based on indicators of oxygen free radical activity and on the changes in behavior of the lipoprotein membrane (O-phosphoserine) in the skeletal muscle of rats.