Furthermore, we identified association of some neurophysiological features with disease severity. These findings provide a set of potential non-invasive and translatable biomarkers that can be utilized in preclinical therapy trials in animal models of RTT and eventually within the context of clinical trials.Biosynthesis of Nylon 12 monomer using dodecanoic acid (DDA) or its esters as the renewable feedstock typically involves ω-hydroxylation, oxidation and ω-amination. The dependence of hydroxylation and oxidation-catalyzing enzymes on redox cofactors, and the requirement of L-alanine as the co-substrate and pyridoxal 5′-phosphate (PLP) as the coenzyme for transamination, raise the issue of redox imbalance and cofactor shortage, challenging the development of efficient biocatalysts. Simultaneous regeneration of the redox equivalents, PLP and L-alanine required in the artificial pathway was enabled by its interfacing with the native metabolism of the host using glucose dehydrogenase (GDH), L-alanine dehydrogenase (AlaDH) and an exogenous ribose 5-phosphate (R5P)-dependent PLP synthesis pathway as bridges. TGF-beta activation Further engineering of the host by blocking β-oxidation and enhancing substrate uptake improved the ω-aminododecanoic acid (ω-AmDDA) yield to 96.5%. This study offers a strategy to resolve the cofactor imbalance issue commonly encountered in whole-cell biocatalysis and meanwhile lays a solid foundation for Nylon 12 bioproduction.Metabolic engineering has allowed the production of a diverse number of valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow the commercialization of metabolically engineered systems. Dynamic metabolic engineering is a rapidly developing field that seeks to address these challenges through the design of genetically encoded metabolic control systems which allow cells to autonomously adjust their flux in response to their external and internal metabolic state. This review first discusses theoretical works which provide mechanistic insights and design choices for dynamic control systems including two-stage, continuous, and population behavior control strategies. Next, we summarize molecular mechanisms for various sensors and actuators which enable dynamic metabolic control in microbial systems. Finally, important applications of dynamic control to the production of several metabolite products are highlighted, including fatty acids, aromatics, and terpene compounds. Altogether, this review provides a comprehensive overview of the progress, advances, and prospects in the design of dynamic control systems for improved titer, rate, and yield metrics in metabolic engineering.

To provide a methodology for estimating the effect of U.S.-based Certified Electronic Health Records Technology (CEHRT) implemented by primary care physicians (PCPs) on a Healthcare Effectiveness Data and Information Set (HEDIS) measure for childhood immunization delivery.

This study integrates multiple health care administrative data sources from 2010 through 2014, analyzed through an interrupted time series design and a hierarchical Bayesian model. We compared managed care physicians using CEHRT to propensity-score matched comparisons from network physicians who did not adopt CEHRT. Inclusion criteria for physicians using CEHRT included attesting to the Childhood Immunization Status clinical quality measure in addition to meeting “Meaningful Use” (MU) during calendar year 2013. We used a first-presence patient attribution approach to develop provider-specific immunization scores.

We evaluated 147 providers using CEHRT, with 147 propensity-score matched providers selected from a pool of 1253 PCPs practf propensity-score matched provider populations to estimate the impact of CEHRT on outcomes-based quality measures such as childhood immunization delivery.Visualizing bone mineralization and collagen fibril organization at intermediate scales between the nanometer and the hundreds of microns range, is still an important challenge. Similarly, visualizing cellular components which locally affect the tissue structure requires a precision of a few tens of nanometers at maximum while spanning several tens of micrometers. In the last decade, gallium focused ion beam (FIB) equipped with a scanning electron microscope (SEM) proved to be an extremely valuable structural tool to meet those ends. In this study, we assess the capability of a recent plasma FIB-SEM technology which provides a potential increase in measurement speed over gallium FIB-SEM, thus paving the way to larger volume analysis. Nanometer-scale layers of demineralized and mineralized unstained human femoral lamellar bone were sequentially sectioned over volumes of 6-16,000 μm3. Analysis of mineralized tissue revealed prolate ellipsoidal mineral clusters measuring approximately 1.1 µm in length by 700 nm at their maximum diameter. Those features, suggested by others in high resolution studies, appear here as a ubiquitous motif in mineralized lamellar bone over thousands of microns cubed, suggesting a heterogeneous and yet regular pattern of mineral deposition past the single collagen fibril level. This large scale view retained sufficient resolution to visualize the collagen fibrils while also partly visualizing the lacuno-canalicular network in three-dimensions. These findings are strong evidence for suitability of PFIB as a bone analysis tool and the need to revisit bone mineralization over multi-length scales with mineralized tissue.

To evaluate associations between counties’ COVID-19 cases and racial-ethnic and nativity composition, considering heterogeneity across Latin American-origin subgroups and regions of the United States.

Using county-level data and multilevel negative binomial models, we evaluate associations between COVID-19 cases and percentages of residents that are foreign-born, Latinx, Black, or Asian, presenting estimates for all counties combined and stratifying across regions. Given varying risk factors among Latinx, we also evaluate associations for percentages of residents from specific Latin American-origin groups.

Percentage of foreign-born residents is positively associated with COVID-19 case rate (IRR= 1.106; 95% CI 1.074-1.139). Adjusted associations for percentage Latinx are nonsignificant for all counties combined, but this obscures heterogeneity. Counties with more Central Americans have higher case rates (IRR= 1.130; 95% CI 1.067-1.197). And, in the Northeast and Midwest, counties with more Puerto Ricans have higher case rates.