The purpose of this work was to evaluate solid lipid nanoparticles (SLNs) as a long acting injectable drug delivery platform for intramuscular and subcutaneous administration. SLNs were developed with a low (unsaturated) and high (supersaturated) drug concentration at equivalent lipid doses. The impact of the drug loading as well as the administration route for the SLNs using two model compounds with different physicochemical properties were explored for their in vitro and in vivo performance. Results revealed that drug concentration had an influence on the particle size and entrapment efficiency of the SLNs and, therefore, indirectly an influence on the Cmax/dose and AUC/dose after administration to rats. Furthermore, the in vitro drug release was compound specific, and linked to the affinity of the drug compounds towards the lipid matrix and release medium. The pharmacokinetic parameters resulted in an increased tmax, t1/2 and mean residence time (MRT) for all formulations after intramuscular and subcutaneous dosing, when compared to intravenous administration. Whereas, the subcutaneous injections performed better for those parameters than the intramuscular injections, because of the higher blood perfusion in the muscles compared with the subcutaneous tissues. In conclusion, SLNs extend drug release, need to be optimized for each drug, and are appropriate carriers for the delivery of drugs that require a short-term sustained release in a timely manner.Colorectal cancer (CRC) is one of the most common human malignancies accounting for approximately 10 % of worldwide cancer incidence and mortality. While early-stage CRC is mainly a preventable and curable disease, metastatic colorectal cancer (mCRC) remains an unmet clinical need. Moreover, about 25 % of CRC cases are diagnosed only at the metastatic stage. Despite the extensive molecular and functional knowledge on this disease, systemic therapy for mCRC still relies on traditional 5-fluorouracil (5-FU)-based chemotherapy regimens. On the other hand, targeted therapies and immunotherapy have shown effectiveness only in a limited subset of patients. For these reasons, there is a growing need to define the molecular and biological landscape of individual patients to implement novel, rationally driven, tailored therapies. In this review, we explore current and emerging approaches for CRC management such as genomic, transcriptomic and metabolomic analysis, the use of liquid biopsies and the implementation of patients' preclinical avatars. In particular, we discuss the contribution of each of these tools in elucidating patient specific features, with the aim of improving our ability in advancing the diagnosis and treatment of colorectal tumors.Personality traits reflect key aspects of individual variability in different psychological domains. Understanding the mechanisms that give rise to these differences requires an exhaustive investigation of the behaviors associated with such traits, and their underlying neural sources. Here we investigated the mechanisms underlying agreeableness, one of the five major dimensions of personality, which has been linked mainly to socio-cognitive functions. In particular, we examined whether individual differences in the neural representations of social information are related to differences in agreeableness of individuals. To this end, we adopted a multivariate representational similarity approach that captured within single individuals the activation pattern similarity of social and non-social content, and tested its relation to the agreeableness trait in a hypothesis-driven manner. The main result confirmed our prediction processing social and non-social content led to similar patterns of activation in individuals with low agreeableness, while in more agreeable individuals these patterns were more dissimilar. Critically, this association between agreeableness and encoding similarity of social and random content was significant only in the dorsomedial prefrontal cortex, a brain region consistently involved during attributions of mental states. The present finding reveals the link between neural mechanisms underlying social information processing and agreeableness, a personality trait highly related to socio-cognitive abilities, thereby providing a step forward in characterizing its neural determinants. Furthermore, it emphasizes the advantage of multivariate pattern analysis approaches in capturing and understanding the neural sources of individual variations.Functional connectivity (FC) and resting-state network (RSN) analyses using functional magnetic resonance imaging (fMRI) have evolved into a growing field of research and have provided useful biomarkers for the assessment of brain function in neurological disorders. However, the underlying mechanisms of the blood oxygen level-dependant (BOLD) signal are not fully resolved due to its inherent complexity.  https://www.selleckchem.com/products/Oridonin(Isodonol).html  In contrast, [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) has been shown to provide a more direct measure of local synaptic activity and may have additional value for the readout and interpretation of brain connectivity. We performed an RSN analysis from simultaneously acquired PET/fMRI data on a single-subject level to directly compare fMRI and [18F]FDG-PET-derived networks during the resting state. Simultaneous [18F]FDG-PET/fMRI scans were performed in 30 rats. Pairwise correlation analysis, as well as independent component analysis (ICA), were used to compare the readouts of both methderived FC. However, several brain regions were exclusively attributed to either [18F]FDG or BOLD-derived networks underlining the complementarity of this hybrid imaging approach, which may contribute to the understanding of brain functional organization and could be of interest for future clinical applications.Neural oscillations constitute an intrinsic property of functional brain organization that facilitates the tracking of linguistic units at multiple time scales through brain-to-stimulus alignment. This ubiquitous neural principle has been shown to facilitate speech segmentation and word learning based on statistical regularities. However, there is no common agreement yet on whether speech segmentation is mediated by a transition of neural synchronization from syllable to word rate, or whether the two time scales are concurrently tracked. Furthermore, it is currently unknown whether syllable transition probability contributes to speech segmentation when lexical stress cues can be directly used to extract word forms. Using Inter-Trial Coherence (ITC) analyses in combinations with Event-Related Potentials (ERPs), we showed that speech segmentation based on both statistical regularities and lexical stress cues was accompanied by concurrent neural synchronization to syllables and words. In particular, ITC at the word rate was generally higher in structured compared to random sequences, and this effect was particularly pronounced in the flat condition.