Explore the vast range of titles available.

Among patients with occlusion of a large intracerebral vessel who had a clinical deficit that was disproportionately severe relative to the infarct volume, 90-day outcomes for disability were better with late thrombectomy plus standard care than with standard care alone.

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment. Small intestinal bacterial overgrowth (SIBO) has been associated with functional gastrointestinal disorders. Here, the authors show that SIBO may be a result of dietary preferences, and patient symptoms correlate with changes in small intestinal microbial composition but not with SIBO.

A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies. Although microbial communities are associated with human, environmental, plant, and animal health, there exists no cost-effective method for precisely characterizing species and genes in such communities. While deep whole-metagenome shotgun (WMS) sequencing provides high taxonomic and functional resolution, it is often prohibitively expensive for large-scale studies. The prevailing alternative, 16S rRNA gene amplicon (16S) sequencing, often does not resolve taxonomy past the genus level and provides only moderately accurate predictions of the functional profile; thus, there is currently no widely accepted approach to affordable, high-resolution, taxonomic, and functional microbiome analysis. To address this technology gap, we evaluated the information content of shallow shotgun sequencing with as low as 0.5 million sequences per sample as an alternative to 16S sequencing for large human microbiome studies. We describe a library preparation protocol enabling shallow shotgun sequencing at approximately the same per-sample cost as 16S sequencing. We analyzed multiple real and simulated biological data sets, including two novel human stool samples with ultradeep sequencing of 2.5 billion sequences per sample, and found that shallow shotgun sequencing recovers more-accurate species-level taxonomic and functional profiles of the human microbiome than 16S sequencing. We discuss the inherent limitations of shallow shotgun sequencing and note that 16S sequencing remains a valuable and important method for taxonomic profiling of novel environments. Although deep WMS sequencing remains the gold standard for high-resolution microbiome analysis, we recommend that researchers consider shallow shotgun sequencing as a useful alternative to 16S sequencing for large-scale human microbiome research studies where WMS sequencing may be cost-prohibitive. IMPORTANCE A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies.

It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.

Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked cellular context critical to mechanistic understanding of how rejection occurs despite immunosuppression (IS). We performed combined single-cell RNA transcriptomic and TCR-α/β sequencing on rBx from patients with ACR under differing IS drugs: tacrolimus, iscalimab, and belatacept. We found distinct CD8+ T cell phenotypes (e.g., effector, memory, exhausted) depending upon IS type, particularly within expanded CD8+ T cell clonotypes (CD8EXP). Gene expression of CD8EXP identified therapeutic targets that were influenced by IS type. TCR analysis revealed a highly restricted number of CD8EXP, independent of HLA mismatch or IS type. Subcloning of TCR-α/β cDNAs from CD8EXP into Jurkat 76 cells (TCR-/-) conferred alloreactivity by mixed lymphocyte reaction. Analysis of sequential rBx samples revealed persistence of CD8EXP that decreased, but were not eliminated, after successful antirejection therapy. In contrast, CD8EXP were maintained in treatment-refractory rejection. Finally, most rBx-derived CD8EXP were also observed in matching urine samples, providing precedent for using urine-derived CD8EXP as a surrogate for those found in the rejecting allograft. Overall, our data define the clonal CD8+ T cell response to ACR, paving the next steps for improving detection, assessment, and treatment of rejection.

Living systems employ cilia to control and to sense the flow of fluids for many purposes, such as pumping, locomotion, feeding, and tissue morphogenesis. Beyond their use in biology, functional arrays of artificial cilia have been envisaged as a potential biomimetic strategy for inducing fluid flow and mixing in lab-on-a-chip devices. Here we report on fluid transport produced by magnetically actuated arrays of biomimetic cilia whose size approaches that of their biological counterparts, a scale at which advection and diffusion compete to determine mass transport. Our biomimetic cilia recreate the beat shape of embryonic nodal cilia, simultaneously generating two sharply segregated regimes of fluid flow: Above the cilia tips their motion causes directed, long-range fluid transport, whereas below the tips we show that the cilia beat generates an enhanced diffusivity capable of producing increased mixing rates. These two distinct types of flow occur simultaneously and are separated in space by less than 5 μm, approximately 20% of the biomimetic cilium length. While this suggests that our system may have applications as a versatile microfluidics device, we also focus on the biological implications of our findings. Our statistical analysis of particle transport identifying an enhanced diffusion regime provides novel evidence for the existence of mixing in ciliated systems, and we demonstrate that the directed transport regime is Poiseuille–Couette flow, the first analytical model consistent with biological measurements of fluid flow in the embryonic node.

The repair of functional innervated and vascularized skeletal muscle from severe injuries, such as critical limb ischemia, denervation, and volumetric muscle loss, remains a critical clinical challenge. Regenerative cell therapies are often hindered by donor site morbidities and rapid clearance from injured tissue. Furthermore, emerging tissue engineering and biomaterials approaches are often stifled by-and may even worsen-the chronic, inflammatory microenvironment that debilitates these sites of muscle injury, as well as the underlying peripheral nerves and microvessels. Consequently, the role of the immune system in tissue repair has been increasingly studied and capitalized upon in the design of regenerative biomaterials to overcome these challenges. In this review, recent strategies for the development of immunomodulatory biomaterials for vascularized and innervated skeletal muscle repair will be discussed within the context of muscle, nervous, and vascular tissues, as well as the respective roles of immune cells and tissue progenitors during these repair processes. These strategies span chemical functionalization, sustained presentation of immunomodulatory cues, and inflammatory responses to natural and synthetic biomaterials, among other approaches.

Objective: The Neonatal Resuscitation Program (NRP) has transitioned to a simulation-based format. We hypothesized that immersive simulation differentially impacts similar trainee populations’ resuscitation knowledge, procedural skill and teamwork behavior. Study Design: Residents from NICU and non-NICU programs were randomized to either control or a booster simulation 7 to 10 months after NRP. Procedural skill and teamwork behavior instruments were validated. Individual resident’s resuscitation performance was assessed at 15 to 18 months. Three reviewers rated videos. Result: Fifty residents were assessed. Inter-rater reliability was good for procedural skills (0.78) and team behavior (0.74) instruments. The intervention group demonstrated better procedural skills (71.6 versus 64.4) and teamwork behaviors (18.8 versus 16.2). The NICU program demonstrated better teamwork behaviors (18.6 versus 15.5) compared with non-NICU program. Conclusion: A simulation-enhanced booster session 9 months after NRP differentiates procedural skill and teamwork behavior at 15 months. Deliberate practice with simulation enhances teamwork behaviors additively with residents’ clinical resuscitation exposure.

Synthetic polymeric materials are rapidly replacing more traditional inorganic materials, such as metals, and natural polymeric materials, such as wood. As these synthetic materials are flammable, they require modifications to decrease their flammability through the addition of flame-retardant compounds. Environmental regulation has restricted the use of some halogenated flame-retardant additives, initiating a search for alternative flame-retardant additives. Nanoparticle fillers are highly attractive for this purpose, because they can simultaneously improve both the physical and flammability properties of the polymer nanocomposite. We show that carbon nanotubes can surpass nanoclays as effective flame-retardant additives if they form a jammed network structure in the polymer matrix, such that the material as a whole behaves rheologically like a gel. We find this kind of network formation for a variety of highly extended carbon-based nanoparticles: single- and multiwalled nanotubes, as well as carbon nanofibres.

River deltas have contributed to atmospheric carbon regulation throughout Earth history, but functioning in the modern era has been impaired by reduced sediment loads, altered hydrologic regimes, increased global sea-level rise and accelerated subsidence. Delta restoration involves environmental engineering via river diversions, which utilize self-organizing processes to create prograding deltas. Here we analyse sediment cores from Wax Lake delta, a product of environmental engineering, to quantify the burial of organic carbon. We find that, despite relatively low concentrations of organic carbon measured in the cores (about 0.4%), the accumulation of about 3 T m −2 of sediment over the approximate 60 years of delta building resulted in the burial of a significant amount of organic carbon (16 kg m −2 ). This equates to an apparent organic carbon accumulation rate of 250 ± 23 g m −2  yr −1 , which implicitly includes losses by carbon emissions and erosion. Our estimated accumulation rate for Wax Lake delta is substantially greater than previous estimates based on the top metre of delta sediments and comparable to those of coastal mangrove and marsh habitats. The sedimentation of carbon at the Wax Lake delta demonstrates the capacity of engineered river diversions to enhance both coastal accretion and carbon burial. Substantial amounts of organic carbon have been buried in the Wax Lake delta, USA, over the past 20 years, according to sediment analyses. This suggests that river diversions can lead to both coastal accretion and carbon sequestration.