Discovery and Preclinical Characterization of BIIB129, a Covalent, Selective, and Brain-Penetrant BTK Inhibitor for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic disease with an underlying pathology characterized by inflammation-driven neuronal loss, axonal injury, and demyelination. Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase and member of the TEC family of kinases, is involved in the regulation, migration, and functional activation of B cells and myeloid cells in the periphery and the central nervous system (CNS), cell types which are deemed central to the pathology contributing to disease progression in MS patients. Herein, we describe the discovery of BIIB129 (), a structurally distinct and brain-penetrant targeted covalent inhibitor (TCI) of BTK with an unprecedented binding mode responsible for its high kinome selectivity.

Co-Extraction Technique Improves Functional Capacity and Health-Related Benefits of Olive Oils: A Mini Review.

Olive oil, a fundamental component of the Mediterranean diet, is recognized as a functional food due to its health-promoting composition. The concentration of phenolic compounds in olive oil is influenced by various factors such as genetics, agro-climatic conditions, and technological processes. Therefore, to ensure an ideal intake of phenolics through the diet, it is recommended to produce functional enriched olive oil that contains a high concentration of bioactive compounds.

Stratification of poverty risk: The importance of social class in four European countries.

Social class structures life chances and exposure to socioeconomic risk, but the extent to which this is still the case is subject to debate. While some assert a relevant middle-class squeeze and consequent polarisation, others argue for the disappearance of social class and a 'democratisation' of social and economic risk for all segments of postmodern society. We focused on relative poverty to interrogate the extent to which occupational class still matters and whether traditionally 'safe' middle-class occupations have lost their capacity for sheltering people from socioeconomic risk.

Overcoming Challenges in Pediatric Formulation with a Patient-Centric Design Approach: A Proof-of-Concept Study on the Design of an Oral Solution of a Bitter Drug.

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP).

Lockdown, Earnings Losses and Household Asset Buffers in Europe.

Measures taken to contain the spread of COVID-19 affected some workers' capability to work and hence earning more than others. The initial impact may have been mitigated, for instance by relying on savings and assets, but access to these buffers likely varied within and across countries. In this article we estimate COVID-19 potential earnings losses using the Lockdown Working Ability Index and relate this to households' savings and assets observed in the Eurosystem Household Finance and Consumption Survey.