An In-vivo 1H-MRS short-echo time technique at 7T: Quantification of metabolites in chronic multiple sclerosis and neuromyelitis optica brain lesions and normal appearing brain tissue

Highlights NAAG likely contributes to the total NAA differences between multiple sclerosis lesion and normal appearing brain tissue. myo-Inositol was not shown to be different between chronic AQP4Ab-NMOSD brain lesions and normal appearing brain tissue. An optimised MRS methodology is described, using 7T field strength and correcting for tissue T2 water relaxion differences. 7-tesla MRS profiles of chronic brain lesions and normal appearing white matter are presented for MS and AQP4Ab-NMOSD. Abstract Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain lesions in 11 MS and 4 AQP4Ab-NMOSD patients using an optimised MRS methodology at ultra-high field strength (7T) incorporating correction for T2 water relaxation differences between lesioned and normal tissue. MS metabolite results were in keeping with the existing literature: total N-acetylaspartate (NAA) was lower in lesions compared to normal appearing brain white matter (NAWM) with reciprocal findings for myo-Inositol. An unexpected subtlety revealed by our technique was that total NAA differences were likely driven by NAA-glutamate (NAAG), a ubiquitous CNS molecule with functions quite distinct from NAA though commonly quantified together with NAA in MRS studies as total NAA. Surprisingly, AQP4Ab-NMOSD showed no significant differences for total NAA, NAA, NAAG or myo-Inositol between lesion and NAWM sites, nor were there any differences between MS and AQP4Ab-NMOSD for a priori hypotheses. Post-hoc testing revealed a significant correlation between NAWM Ins:NAA and disability (as measured by EDSS) for disease groups combined, driven by the AP4Ab-NMOSD group. Utilising an optimised MRS methodology, our study highlights some under-explored subtleties in MRS profiles, such as the absence of myo-Inositol concentration differences in AQP4Ab-NMOSD brain lesions versus NAWM and the potential influence of NAAG differences between lesions and normal appearing white matter in MS

Uma análise socioeconômica das mulheres da Praça da Bandeira

Bebel é um projetoimplementado pela PlaNet Finance Brasil e a ONG Gerando Vida em parceria com a ComissãoEuropeia, a Secretaria de Assistência Social e Direitos Humanos do Rio deJaneiro e a Unisuam,  com o objetivo deoferecer novas oportunidades profissionais e melhores condições de vida parauma população composta de mulheres morando num espaço profundamente segregado eestigmatizado pelas atividades de prostituição, na Praça da Bandeira, ZonaNorte do Rio de Janeiro. Foi realizada uma pesquisa quantitativa com o objetivode verificar a situação socioeconômica de 200 mulheres, sendo que 75 são Trabalhadorasde Sexo na Praça da Bandeira. Dolevantamento, pode-se verificar que a situação socioeconômica do público alvo éprecária e os problemas se situam em vários níveis, tais como: educação, renda,acesso aos serviços públicos, suporte social, etc. Entretanto, é importante ressaltar que tais mulheres têminteresse em continuar a estudar ou em abrir seu próprio negócio. Essamotivação é ainda maior entre as Trabalhadoras de Sexo (TS) do que entre as TrabalhadorasConvencionais (TC). Além disso, foi constatado que muitas mulheres já fizeramum curso profissionalizante, mas não trabalham na área.Os dados coletados no presente estudo pretendem fomentar osdebates públicos para a implantação de políticas públicas adequadas e efetivas,assim como a implantação de suporte psicossocial para as mulheres da Praça daBandeira com o objetivo de desenvolver uma atividade econômica na área domicroempreendedorismo e cursos de profissionalização

Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms

The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicological properties need to be assessed. Accepted methods for gathering the information required by law for approval of substances are often animal methods. To reduce, refine, and replace animal testing, innovative organotypic in vitro models have emerged. Such models appear at different levels of complexity ranging from simpler, self-organized three-dimensional (3D) cell cultures up to more advanced scaffold-based co-cultures consisting of multiple cell types. This review provides an overview of recent developments in the field of toxicity testing with in vitro models for three major organ types: heart, skin, and liver. This review also examines regulatory aspects of such models in Europe and the UK, and summarizes best practices to facilitate the acceptance and appropriate use of advanced in vitro models

An In-vivo 1H-MRS short-echo time technique at 7T: Quantification of metabolites in chronic multiple sclerosis and neuromyelitis optica brain lesions and normal appearing brain tissue

Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Abpositive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain lesions in 11 MS and 4 AQP4Ab-NMOSD patients using an optimised MRS methodology at ultrahigh field strength (7T) incorporating correction for T2 water relaxation differences between lesioned and normal tissue. MS metabolite results were in keeping with the existing literature: total N-acetylaspartate (NAA) was lower in lesions compared to normal appearing brain white matter (NAWM) with reciprocal findings for myo-Inositol. An unexpected subtlety revealed by our technique was that total NAA differences were likely driven by NAA-glutamate (NAAG), a ubiquitous CNS molecule with functions quite distinct from NAA though commonly quantified together with NAA in MRS studies as total NAA. Surprisingly, AQP4Ab-NMOSD showed no significant differences for total NAA, NAA, NAAG or myo-Inositol between lesion and NAWM sites, nor were there any differences between MS and AQP4Ab-NMOSD for a priori hypotheses. Post-hoc testing revealed a significant correlation between NAWM Ins:NAA and disability (as measured by EDSS) for disease groups combined, driven by the AP4Ab-NMOSD group. Utilising an optimised MRS methodology, our study highlights some under-explored subtleties in MRS profiles, such as the absence of myo-Inositol concentration differences in AQP4Ab-NMOSD brain lesions versus NAWM and the potential influence of NAAG differences between lesions and normal appearing white matter in MS