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Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the “one-treatment fits all” approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex “-omics” data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.

Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied—which has implications for drug safety and effective use in Africa.Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations.Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.

The idea that cellular stress (including that precipitated by stretch), plays a significant role in the mechanisms initiating parturition, has gained considerable traction over the last decade. One key consequence of this cellular stress is the increased production of Danger Associated Molecular Patterns (DAMPs). This diverse family of molecules are known to initiate inflammation through their interaction with Pattern Recognition Receptors (PRRs) including, Toll-like receptors (TLRs). TLRs are the key innate immune system surveillance receptors that detect Pathogen Associated Molecular Patterns (PAMPs) during bacterial and viral infection. This is also seen during Chorioamnionitis. The activation of TLR commonly results in the activation of the pro-inflammatory transcription factor Nuclear Factor Kappa-B (NF-kB) and the downstream production of pro-inflammatory cytokines. It is thought that in the human fetal membranes both DAMPs and PAMPs are able, perhaps via their interaction with PRRs and the induction of their downstream inflammatory cascades, to lead to both tissue remodeling and weakening. Due to the high incidence of infection-driven Pre-Term Birth (PTB), including those that have preterm Premature Rupture of the Membranes (pPROM), the role of TLR in fetal membranes with Chorioamnionitis has been the subject of considerable study. Most of the work in this field has focused on the effect of PAMPs on whole pieces of fetal membrane and the resultant inflammatory cascade. This is important to understand, in order to develop novel prevention, detection, and therapeutic approaches, which aim to reduce the high number of mothers suffering from infection driven PTB, including those with pPROM. Studying the role of sterile inflammation driven by these endogenous ligands (DAMPs) activating PRRs system in the mesenchymal and epithelial cells in the amnion is important. These cells are key for the maintenance of the integrity and strength of the human fetal membranes. This review aims to (1) summarize the knowledge to date pertinent to the role of DAMPs and PRRs in fetal membrane weakening and (2) discuss the clinical potential brought by a better understanding of these pathways by pathway manipulation strategies.

Background: There is a correlation between self-esteem in adolescents and risks and protective factors for their health and welfare. The study was conducted to determine the prevalence of low self-esteem and sociodemographic features related to anxiety, depression, educational stress, and suicidal ideation in secondary school students in Vietnam.Methods: A cross-sectional design was employed for this study with participation of 1,149 students in Cantho City in Vietnam. A structured questionnaire was applied to ask about self-esteem, depression, anxiety, educational stress, and suicidal ideation.Results: Students with low self-esteem were detected at a prevalence of 19.4%. High educational stress and physical and emotional abuse by parents or other adults in the household were major risk factors correlated to low self-esteem, while a protective factor for low self-esteem was attending supplementary classes. An association among lower self-esteem and increased anxiety, depression, and suicidal ideation was detected.Conclusions: Self-esteem is associated with anxiety, depression, and academic stress, which significantly affect students’ quality of life and links to suicidal ideation. These results therefore suggested the need for a school-based or web-based provision aimed at proactively increasing students’ self-esteem and skills for dealing with academic stress.

We conducted a neurophysiological study of attempted speech production in a paralyzed human volunteer using chronic microelectrode recordings. The volunteer suffers from locked-in syndrome leaving him in a state of near-total paralysis, though he maintains good cognition and sensation. In this study, we investigated the feasibility of supervised classification techniques for prediction of intended phoneme production in the absence of any overt movements including speech. Such classification or decoding ability has the potential to greatly improve the quality-of-life of many people who are otherwise unable to speak by providing a direct communicative link to the general community. We examined the performance of three classifiers on a multi-class discrimination problem in which the items were 38 American English phonemes including monophthong and diphthong vowels and consonants. The three classifiers differed in performance, but averaged between 16-21% overall accuracy (chance-level is 1/38 or 2.6%). Further, the distribution of phonemes classified statistically above chance was non-uniform though 20 of 38 phonemes were classified with statistical significance for all three classifiers. These preliminary results suggest supervised classification techniques are capable of performing large scale multi-class discrimination for attempted speech production and may provide the basis for future communication prostheses.