Scalable solvent-free production of liposomes

Objectives. A major challenge faced with the manufacture of liposomes is the high volumes of organic solvents used and disposed of during manufacturing. Therefore, we have implemented an organic solvent-free production method for drug-loaded liposomes and demonstrated its applicability with both aqueous core loaded and bilayer loaded drugs. Methods. Liposomes were produced by high-shear mixing dry powder lipids with an aqueous buffer, followed by down-sizing using a Microfluidizer® processor. Liposomes were purified via tangential flow filtration and characterised in terms of size, polydispersity, zeta potential and drug loading. Key findings. Doxorubicin-loaded PEGylated liposomes can be manufactured using this solvent-free method with particle sizes of 100-110 nm, low PDI (<0.2) and high drug loading (97 - 98%). If required, liposomes can be further down-sized via further microfluidic processing without impacting drug loading. Similar results were achieved with non-PEGylated liposomes. With bilayer loaded amphotericin B liposomes, again liposomes can be prepared within a clinically appropriate size range (100 – 110 nm in size, low PDI) with high drug loading (98 - 100 %). Conclusions. We apply a simple and scalable solvent-free method for the production of both aqueous core or bilayer drug loaded liposomes

The high energy Universe at ultra-high resolution: the power and promise of X-ray interferometry

We propose the development of X-ray interferometry (XRI), to reveal the Universe at high energies with ultra-high spatial resolution. With baselines which can be accommodated on a single spacecraft, XRI can reach 100 μ as resolution at 10 Å (1.2 keV) and 20 μ as at 2 Å (6 keV), enabling imaging and imaging-spectroscopy of (for example) X-ray coronae of nearby accreting supermassive black holes (SMBH) and the SMBH ‘shadow’; SMBH accretion flows and outflows; X-ray binary winds and orbits; stellar coronae within ∼ 100 pc and many exoplanets which transit across them. For sufficiently luminous sources XRI will resolve sub-pc scales across the entire observable Universe, revealing accreting binary SMBHs and enabling trigonometric measurements of the Hubble constant with X-ray light echoes from quasars or explosive transients. A multi-spacecraft ‘constellation’ interferometer would resolve well below 1 μ as, enabling SMBH event horizons to be resolved in many active galaxies and the detailed study of the effects of strong field gravity on the dynamics and emission from accreting gas close to the black hole

Tuberculose na Atenção Primária à Saúde: estudo de uma área de alta incidência sob o enfoque da vigilância epidemiológica

Resumo: a tuberculose continua sendo um problema de saúde pública no Brasil. A descentralização das ações de controle e o exercício da vigilância epidemiológica no âmbito da atenção primária à saúde têm importância destacada neste cenário. Porto Alegre é um município prioritário para o controle da tuberculose. Dentro dos municípios prioritários, existem áreas críticas ditas bolsões de tuberculose e dentro dos bairros existem também micro-áreas com densidade maior de casos. Objetivos: o objetivo geral deste estudo foi identificar os casos de tuberculose ocorridos em uma micro-área de pobreza considerada suspeita de ser um bolsão de tuberculose. Os objetivos específicos foram comparar dados obtidos por diferentes métodos de coleta, desenvolver uma investigação detalhada dos casos e seus contatos e verificar a existência de associações temporais e espaciais entre os casos. Materiais e Métodos: foi realizado um estudo de uma série de casos com base em um levantamento epidemiológico dos casos notificados ao SINAN entre 2000 e 2008 e feita uma comparação destas notificações com os casos identificados em um inquérito epidemiológico prévio. Para a busca de dados não disponíveis no banco do SINAN, foi realizada uma investigação epidemiológica de campo. Resultados: o coeficiente de incidência desta área restrita em 2005 foi 1550,39 ? 100.000 habitantes, 11 vezes maior do que na área total da gerência distrital e 14 vezes maior do que em toda a área da UBS. Escolaridade e renda dos participantes foram baixas, enquanto que a associação com alcoolismo e a situação de abandono do tratamento foram elevadas. A associação com HIV, diferentemente do que se observa no panorama geral da cidade, foi baixa. A investigação dos contatos ficou abaixo do preconizado. O índice da relação contatos/caso examinados foi registrado como zero em 12 das 21 notificações e em apenas 4 a meta mínima de examinar 4 contatos por caso foi atingida ou superada. Houve vários casos entre contatos domiciliares e também foram descritos contatos extra-domiciliares. Conclusões: estudos epidemiológicos diversos podem ter papéis complementares na execução das tarefas de vigilância. A implementação de ações para diminuir o impacto da tuberculose na saúde da população inclui diversos setores. A atenção primária à saúde ocupa um papel de destaque nesse cenário

The Aged Striatum : Evidence of Molecular and Structural Changes Using a Longitudinal Multimodal Approach in Mice

To study the aging human brain requires significant resources and time. Thus, mice models of aging can provide insight into changes in brain biological functions at a fraction of the time when compared to humans. This study aims to explore changes in dopamine D1 and D2 receptor availability and of gray matter density in striatum during aging in mice and to evaluate whether longitudinal imaging in mice may serve as a model for normal brain aging to complement cross-sectional research in humans. Mice underwent repeated structural magnetic resonance imaging (sMRI), and [11C]Raclopride and [11C]SCH23390 positron emission tomography (PET) was performed on a subset of aging mice. PET and sMRI data were analyzed by binding potential (BP ND ), voxel- and tensor-based morphometry (VBM and TBM, respectively). Longitudinal PET revealed a significant reduction in striatal BP ND for D2 receptors over time, whereas no significant change was found for D1 receptors. sMRI indicated a significant increase in modulated gray matter density (mGMD) over time in striatum, with limited clusters showing decreased mGMD. Mouse [11C]Raclopride data is compatible with previous reports in human cross-sectional studies, suggesting that a natural loss of dopaminergic D2 receptors in striatum can be assessed in mice, reflecting estimates from humans. No changes in D1 were found, which may be attributed to altered [11C]SCH23390 kinetics in anesthetized mice, suggesting that this tracer is not yet able to replicate human findings. sMRI revealed a significant increase in mGMD. Although contrary to expectations, this increase in modulated GM density may be attributed to an age-related increase in non-neuronal cells

Host galaxies of merging compact objects: Mass, star formation rate, metallicity, and colours

Characterizing the properties of the host galaxies of merging compact objects provides essential clues to interpret current and future gravitational-wave detections. Here, we investigate the stellar mass, star formation rate (SFR), metallicity, and colours of the host galaxies of merging compact objects in the local Universe by combining the results of MOBSE population-synthesis models together with galaxy catalogues from the EAGLE simulation.We predict that the stellar mass of the host galaxy is an excellent tracer of themerger rate per galaxy nGW of double neutron stars (DNSs), double black holes (DBHs), and black hole neutron star binaries (BHNSs). We find a significant correlation also between nGW and SFR. As a consequence, nGW correlates also with the r-band luminosity and with the g - r colour of the host galaxies. Interestingly, =60 per cent, =64 per cent, and =73 per cent of all the DNSs, BHNSs, and DBHs merging in the local Universe lie in early-type galaxies, such as NGC 4993. We predict a local DNS merger rate density of ~238 Gpc-3 yr-1 and a DNS merger rate ~16 121 Myr-1 for Milky Way-like galaxies. Thus, our results are consistent with both the DNS merger rate inferred from GW170817 and the one inferred from Galactic DNSs