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Background/Objective: Previous small studies have shown that prenatal opioid-exposed (POE) infants and older children display decreased cerebral, cerebellar, or subcortical brain volumes. However, these studies are plagued by suboptimal reference standards or were unable to correct for the influence of other environmental factors in older children. Therefore, our goal was to study differences in brain volume of POE infants when compared to a geographically matched population. We hypothesized that there will be a significant decrease in total brain volume of the POE infants in comparison to the non-opioid exposed control infants, including a reduction in the cerebellar volume. Methods: This was an IRB approved prospective study of mothers and infants with POE and controls without POE. All recruited infants underwent MRI scans of the brain before they reached a corrected age of 2 months. The T1-weighted MRI images were analyzed by Infant FreeSurfer and segmented into ROIs. The segmentations were manually checked and edited. An ANOVA analysis was performed to compare the cerebellar and total brain volume datasets. We corrected for gender, corrected gestational age at MRI scan, and total brain volume where necessary. Results: 42 infants were included in the study, 21 with POE and 21 control infants. There was a significant difference in the mean gestational age of POE infants (38.28±2.13) compared to control infants (39.42±0.72). On quantitative analysis, the POE group had a significantly reduced total brain and supratentorial volume in comparison to the controls. The cerebellar volume was also significantly smaller in POE, but this significance did not persist when the total brain volume was included in the model. Conclusion: The supratentorial region is affected disproportionately more than the cerebellum in POE. Specific reductions in cortical, subcortical, and white matter volume need to be further investigated and their influence on developmental outcomes need to be studied.

Background/Objective: Prenatal opioid exposure (POE) is a growing public health issue that can result in premature birth, Neonatal Abstinence Syndrome (NAS), and adverse neurodevelopmental outcomes. However, the neural basis for these findings remains relatively unknown. In this study, we aimed to investigate the neural correlates of POE based on neonatal thalamocortical functional connectivity using resting state functional magnetic resonance imaging (rs-fMRI). Methods: In this prospective, IRB-approved study, nineteen neonates with POE and twenty opioid naive (ON) controls underwent non-invasive MRI during natural sleep at mean post-menstrual age (PMA) of 44.7 ± 2.6 and 44.6 ± 2.6 weeks respectively. MR imaging included anatomic T2-weighted images and rs-fMRI. General Linear Model (GLM) seed-based whole brain functional connectivity analysis was performed for each subject, with the right and left thalamus as distinct seed regions. Unpaired mixed-effects group analyses between POE and ON groups were conducted for each seed region corrected for PMA and sex. Results: Thalamic connectivity to cortical and subcortical structures differed in the POE group compared to the ON control group. The POE group exhibited higher functional connectivity to deep gray structures, frontal, medial prefrontal, parietal, occipital, and anterior temporal cortices compared to controls. The POE group exhibited lower connectivity to the nuclei accumbentes, bilateral caudate nuclei, posterior cingulate gyri, superior frontal gyri, insular, and dorsolateral prefrontal cortices. Conclusion and Potential Impact: Overall, these novel results suggest the presence of opioid exposure-related alterations in thalamic functional connectivity. Given that the thalamus plays a crucial role in early brain development, the described alterations in thalamocortical and thalamic-subcortical connectivity may have implications in stratifying risk and informing treatment for the adverse neurodevelopmental outcomes associated with POE. Future studies should explore the relationship between POE-associated disruptions in thalamic connectivity and developmental outcomes.

This paper studies network routing under uncertain costs. We introduce the notion of regret and present methods to minimize it using data. Given a flow vector and a realization of the uncertainty, the regret experienced by a user on a particular path is the difference between the cost incurred on the path and the minimum cost across all paths connecting the same origin and destination. The network-wide regret is the cumulative regret experienced by all agents. We show that, for a fixed uncertainty, the total regret of all agents is a convex function provided the cost function of each path is affine and monotone. We provide two data-driven methods that minimize the expected value and a specified quantile of the total regret, respectively. Simulations compare our solutions to existing approaches of handling uncertainty in routing games.

The Virus Pathogen Database and Analysis Resource (ViPR, www.ViPRbrc.org) is an integrated repository of data and analysis tools for multiple virus families, supported by the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers (BRC) program. ViPR contains information for human pathogenic viruses belonging to the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Filoviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Picornaviridae, Poxviridae, Reoviridae, Rhabdoviridae and Togaviridae families, with plans to support additional virus families in the future. ViPR captures various types of information, including sequence records, gene and protein annotations, 3D protein structures, immune epitope locations, clinical and surveillance metadata and novel data derived from comparative genomics analysis. Analytical and visualization tools for metadata-driven statistical sequence analysis, multiple sequence alignment, phylogenetic tree construction, BLAST comparison and sequence variation determination are also provided. Data filtering and analysis workflows can be combined and the results saved in personal 'Workbenches' for future use. ViPR tools and data are available without charge as a service to the virology research community to help facilitate the development of diagnostics, prophylactics and therapeutics for priority pathogens and other viruses.

International audience; The activity of synthetic interfering nucleic acids (siRNAs) relies on the capacity of delivery systems to efficiently transport nucleic acids into the cytosol of target cells. The pyridylthiourea-grafted 25KDa polyethylenimine (πPEI) is an excellent carrier for siRNA delivery into cells and it was extensively investigated in this report. Quantification of the siRNA-mediated gene silencing efficiency indicated that the πPEI specific delivery activity at the cell level may be measured and appears relatively constant in various cell lines. Delivery experiments assaying inhibitors of various entry pathways or concanamycin A, an inhibitor of the H+/ATPase vacuolar pump showed that the πPEI/siRNA polyplexes did not require any specific entry mode but strongly relied on vacuolar acidification for functional siRNA delivery. Next, πPEI polyplexes containing a siRNA targeting the transcription factor HIF-1α, known to be involved in tumor progression, were locally injected into mice xenografted with a human glioblastoma. A 55% reduction of the level of the target mRNA was observed at doses comparable to those used in vitro when the πPEI delivery activity was calculated per cell. Altogether, our study underscores the usefulness of "simple"/rough cationic polymers for siRNA delivery despite their intrinsic limitations. The study underscores as well as that bottom-up strategies make sense. The in vitro experiments can precede in vivo administration and be of high value for selection of the carrier with enhanced specific delivery activity and parallel other research aiming at improving synthetic delivery systems for resilience in the blood and for enhanced tissue-targeting capacity.

Background Large databases of genetic data are often biased in their representation. Thus, selection of genetic data with desired properties, such as evolutionary representation or shared genotypes, is problematic. Selection on the basis of epidemiological variables may not achieve the desired properties. Available automated approaches to the selection of influenza genetic data make a tradeoff between speed and simplicity on the one hand and control over quality and contents of the dataset on the other hand. A poorly chosen dataset may be detrimental to subsequent analyses. Results We developed a tool, Tree Pruner, for obtaining a dataset with desired evolutionary properties from a large, biased genetic database. Tree Pruner provides the user with an interactive phylogenetic tree as a means of editing the initial dataset from which the tree was inferred. The tree visualization changes dynamically, using colors and shading, reflecting Tree Pruner actions. At the end of a Tree Pruner session, the editing actions are implemented in the dataset. Currently, Tree Pruner is implemented on the Influenza Research Database (IRD). The data management capabilities of the IRD allow the user to store a pruned dataset for additional pruning or for subsequent analysis. Tree Pruner can be easily adapted for use with other organisms. Conclusions Tree Pruner is an efficient, manual tool for selecting a high-quality dataset with desired evolutionary properties from a biased database of genetic sequences. It offers an important alternative to automated approaches to the same goal, by providing the user with a dynamic, visual guide to the ongoing selection process and ultimate control over the contents (and therefore quality) of the dataset.