Biology subjects

Carlson, M.

Publications and source records attributed to Carlson, M..

18 recordsLinked to original sources

bioRxiv2026

Prenatal immune priming to Plasmodium falciparum is characterized by multi-lineage T-cell responses that are influenced by maternal microchimerism and predict malaria outcomes

In malaria endemic settings, the fetus may be exposed to Plasmodium falciparum (Pf) antigens leading to prenatal immune primming (PIP). The fetus also acquires a graft of maternal cells in utero, a phenomenon known as maternal microchimerism (MMc). We have previously identified that MMc at birth predicts altered malaria susceptibility in early childhood, and we hypothesized that this association may be mediated via two potential mechanisms. First, the fetus may acquire Pf-specific MMc T-cells that directly respond to postnatal parasitemia. Alternatively, MMc may indirectly influence the quantity or quality of PIP. To investigate this hypothesis, infant cord bloods from 97 Malian primigravidae were screened for MMc using qPCR. A subset of ten cord blood mononuclear cells with variable MMc levels were stimulated with purified Pf merozoite extract and activated T-cells were sorted by flow cytometry for scRNAseq analysis. Transcriptional profile was used to differentiate Pf-responsive versus bystander activated T-cells, and MMc cells were identified using the Cellector algorithm. Among Pf-responsive cells, we identified four key populations: activated CD4 T-cells, ZBTB16+ CD4 T-cells, activated V{delta}1+ {gamma}{delta} T-cells, and cytotoxic V{gamma}9V{delta}2+ {gamma}{delta} T-cells. The minority of sorted cells were of MMc origin; however, there was a strong association between the presence of MMc and the quantity and quality of PIP. MMc+ infants had significantly fewer Pf-responsive T-cells, as well as a shifted distribution of these cells with fewer ZBTB16+ CD4 and cytotoxic V{gamma}9V{delta}2+ {gamma}{delta} T-cells. Clinically, MMc was protective from incident parasitemia and febrile malaria, whereas the frequencies of ZBTB16+ CD4 and activated CD4 T-cells were associated with increased risk. Together, these data demonstrate that MMc influences malaria outcomes through regulation of offspring inflammatory responses to Pf.

immunology↗

bioRxiv2026

Moving object generates topographic responses in the majority of entorhinal neurons

Vision is crucial in generating a complex array of responses in rodents during spatial exploration and in humans during memory tasks. These tasks involve other variables too, e.g. multisensory cues in rodents and complex memories in humans. Further, there are major differences between the medial and lateral entorhinal cortical (MEC and LEC) functional cell types. To understand the contribution of purely visual information to entorhinal responses, we presented a simple, moving vertical bar of light to head-fixed mice, without any task or reward. Surprisingly, 66% (2391/3601) of the MEC broad spiking neurons were significantly modulated by the bar position on the screen. Visual tuning in MEC had a pronounced dorsoventral topography --the tuning strength dropped from 79% in the dorsal most quartile to 40% in the ventral most quartile. Unlike major differences in spatial and other codes between MEC and LEC during free foraging experiments, LEC cells showed very similar visual tuning (392/606, 65%), including the dorso-ventral gradient in LEC5. Additionally, the majority of putative interneurons, from MEC as well as LEC, showed similar, widespread visual tuning, unlike spatial tasks. Neurons also encoded the object motion direction (naso-temporal vs. temporo-nasal visual motion) with changes in mean rate, tuning strength and/or tuning location. Such directional nature of visual tuning indicates significant history-dependence or sequence encoding. Consistently, replacing the continuous motion by randomly flashing bar of light abolished bar-tuning in two-thirds of continuous bar-tuned cells and substantially altered tuning in the rest. These results reveal the contribution of purely visual inputs in generating anatomically organized responses in the majority of entorhinal neurons. The prevalence and similarity of visual tuning across all layers of MEC as well as LEC exceeds that of other known functional cell types (like grid cells in MEC or egocentric object tuning/time-cells in LEC) during spatial navigation tasks and could be foundational in understanding entorhinal complexity.

neuroscience↗

bioRxiv2026

Psilocybin collapses visual change detection and drives cortical dynamics toward a state of surprise

Psilocybin profoundly alters visual perception, yet the neuronal mechanisms underlying these effects remain unclear. Here we combined large-scale Neuropixels recordings with cell-type specific optogenetics in head-fixed mice performing a visual change-detection task. Psilocybin severely impaired task performance without overt motor deficits. In cortex, the drug modestly suppressed activity of layer 5 neurons while preserving representations of image identity. By contrast, psilocybin imposed a 4-Hz oscillation on visually evoked activity that preferentially affected neurons encoding image change rather than image identity. Under psilocybin, expected image repetitions aberrantly recruited change-encoding ensembles and shifted cortical population dynamics towards trajectories normally evoked by genuine stimulus changes. These effects were strongest in somatostatin-expressing (SST) interneurons in visual cortex. The strength of this modulation depended on image structure and was greatest for images with clear, continuous contours, which preferentially recruited change-encoding ensembles. These findings demonstrate that psilocybin drives internally generated cortical surprise signals, providing a circuit mechanism for altered perception in the acute psychedelic state.

neuroscience↗

bioRxiv2026

Mapping genome-wide RNA-RNA and RNA-DNA interactions in nuclear hubs of male and female Drosophila cells

Nuclear bodies are nucleoprotein complexes with established functions that target chromatin at specific locations and regulate specific RNA processing functions, thereby influencing gene expression. However, the mechanisms that define how nuclear bodies are targeted to specific locations within the genome where they function remain poorly understood. One significant challenge is capturing and understanding the multiple cell-specific interactions occurring in these complexes, arising from RNA components interacting with each other and with DNA and nucleic acid-binding proteins within the context of the nucleuss three-dimensional organization. Mapping these interactions is critical for elucidating mechanisms such as RNA splicing, a key driver of cell-specific transcript diversity. Here, we use RNA-DNA Split Pool Recognition of Interactions by Tag Extension (RD-SPRITE) to characterize, for the first time, sex-specific RNA-RNA and RNA-DNA interactions in Drosophila S2 (male) and Kc (female) cells. We determined the sex-specific RNA-RNA interaction map within the nucleus and, using RNA-DNA interaction data, pinpointed the target loci of various RNA molecules, including small nuclear RNAs (snRNAs), which are core components of the spliceosome-a ribonucleoprotein complex involved in RNA splicing. Based on RNA-RNA interaction data, we also identified novel long non-coding RNAs that may regulate splicing. Furthermore, we investigated the role of transcription factor (TF) CLAMP in sex-specific targeting of the spliceosome. We generated RD-SPRITE datasets in the presence and absence of CLAMP, a key TF involved in dosage compensation, sex-specific RNA splicing, and chromatin organization. We determined that CLAMP regulates global changes in spliceosomal interactions with chromatin, inhibits aberrant snRNA interactions, and regulates sex-specific interactions of RNAs involved in splicing function. Additionally, our dataset provides a valuable resource for investigating additional processes, such as miRNA-mediated silencing, nucleolar functions of snoRNAs, and Cajal body functions of scaRNAs, among others. To facilitate broad community use, we have developed a computational platform, "FlySprite," that enables Drosophila researchers to explore sex-specific RNA-RNA interactions, as well as DNA targets of RNA clusters, through a user-friendly interface.

genomics↗

bioRxiv2026

A mitochondrial program encodes brain vascular reserve

Brain resilience depends on collateral vessels whose geometries preserve blood flow when primary arteries are perturbed. How these protective vascular architectures are developmentally established remains unknown. Using longitudinal in vivo imaging in zebrafish, we show that mitochondrial state in embryonic angiogenic tip cells encodes the topology of basal and surface brain collateral networks. Mechanistically, microRNA-125a establishes the bioenergetic and redox balance of endothelial tip-cell mitochondria through conserved repression of the metabolic regulator PGC1a. Disruption of the microRNA-125a-PGC1a axis uncouples mitochondrial capacity from redox buffering in developing brain tip cells, redirecting their migration toward sparse, incompletely connected collateral network topologies and increasing adult cerebrovascular vulnerability. Consistent with this mechanism, humans with subclinical cerebrovascular injury exhibit reduced circulating microRNA-125a levels associated with incomplete basal collateral configurations. Together, these findings identify mitochondrial state as an instructive and conserved developmental program that encodes brain vascular reserve.

developmental biology↗

bioRxiv2026

Estradiol modulates neuronal network hyperexcitability in select NDD risk genes

Sex hormone signaling during neurodevelopment may act as a modulator of risk for neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASDs). By conducting a systematic and multi-modal evaluation of estradiol effects across loss-of-function deletions in 36 functionally diverse, large-effect ASD/NDD genes in human induced pluripotent stem cell-derived neurons and larval zebrafish, we uncover convergent and divergent gene-by-estradiol interactions at the transcriptomic, circuit, and behavioral levels. Whereas estradiol partially ameliorates dysregulated expression signatures across all ASD/NDD gene knockouts examined, it selectively and rapidly dampens network hyperexcitability phenotypes in only a subset of ASD/NDD gene knockouts. Two genes, ASH1L and SCN2A, are particularly responsive to estradiol treatment, with dramatic rescue of molecular and cellular effects in human knockout neurons, coupled with behavioral phenotypes in larval zebrafish mutants. The seven most estradiol responsive genes show enhanced protein-protein interaction network connectivity, strong co-expression in specific postnatal time periods, and enrichment in upper-layer mature excitatory neurons. Altogether, we describe distinct estradiol rescue in different modalities, elucidating shared transcriptomic effects as well as gene-specific cellular and behavioral rescue in the context of loss of function mutations of select ASD/NDD genes.

genomics↗

bioRxiv2025

Map of spiking activity underlying change detection in the mouse visual system

Visual behavior requires coordinated activity across hierarchically organized brain circuits. Understanding this complexity demands datasets that are both large-scale (sampling many areas) and dense (recording many neurons in each area). Here we present a database of spiking activity across the mouse visual system--including thalamus, cortex, and midbrain--while mice perform an image change detection task. Using Neuropixels probes, we record from >75,000 high-quality units in 54 mice, mapping area-, cortical layer-, and cell type-specific coding of sensory and motor information. Modulation by task-engagement increased across the thalamocortical hierarchy but was strongest in the midbrain. Novel images modulated cortical (but not thalamic) responses through delayed recurrent activity. Population decoding and optogenetics identified a critical decision window for change detection and revealed that mice use an adaptation-based rather than image-comparison strategy. This comprehensive resource provides a valuable substrate for understanding sensorimotor computations in neural networks.

neuroscience↗

bioRxiv2025

Denoising 7T Structural MRI with Conditional Generative Diffusion Models

Purpose7T MRI offers ultra-high resolution and improved sensitivity for iron deposition in neurodegenerative disorders, but commonly used acquisitions are long and hence challenging, especially for elderly subjects. Efficiently denoising a short acquisition to achieve the image quality of a longer acquisition would be of translational benefit. Materials and MethodsWe introduce a conditional diffusion model derived from generative AI (a 7T Conditional Diffusion Model, 7TCDM) that was trained on native single-acquisition 2D reconstructions and referenced multi-repetition images to guide the denoising process and improve SNR and contrast. 7TCDM model was tested on 2D T2-weighted gradient-echo imaging from 19 participants, including healthy controls and individuals with mild cognitive impairment or Alzheimers disease (AD). 7TCDMs performance was assessed using Mean Squared Error (MSE), Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), and comprehensive reader studies. ResultsReferencing the multi-repetition ground truth, 7TCDM improved the single-acquisition original image by 29.1% in MSE, 5.8% in PSNR, and 9.4% in SSIM, and outperformed convolutional neural network-based models in all metrics. Expert rater evaluations confirmed superior image quality, with significantly enhanced detail and contrast preservation in regions such as the hippocampi, white matter lesions, and small cortical veins. The model also demonstrated robust performance in both the concurrently acquired and publicly available 3D multi-echo gradient echo acquisitions, which the model was not trained on. ConclusionsThe 7T Conditional Diffusion Model provides high-quality denoised images from shorter scans, increasing the feasibility of scanning patients in shorter times while preserving essential anatomical and pathological details.

neuroscience↗

bioRxiv2025

Cerebellum and Plasma Metabolomics Identify Sepsis Biomarkers and MSC-sEV-Mediated Rescue

Septic encephalopathy (SE) is a severe complication of sepsis, characterized by neuroinflammation and metabolic dysfunction, with the cerebellum among the most vulnerable brain regions. Advances in the field have been constrained by the lack of reliable biomarkers for SE detection, incomplete mapping of cerebellar metabolic alterations in SE, and limited insight into the therapeutic mechanisms of human mesenchymal stem cell (MSC)-derived small extracellular vesicle (sEV) therapy. To overcome these challenges, we used a murine sepsis model and conducted integrated metabolomic analyses of cerebellar tissue and plasma, with and without MSC-sEV administration. Cross-compartment analyses identified six plasma metabolites with strong diagnostic potential in mice, three of which (n-acetylputrescine, aspartic acid, and cystathionine) were also observed in the plasma of human septic patients, supporting their promise as translatable biomarker candidates. Sepsis triggered profound cerebellar metabolic dysfunction, suppression of oxidative energy metabolism, and redox imbalance. MSC-sEVs attenuated these disturbances via their bioactive cargo, restoring cellular energetics and reestablishing antioxidant balance. Collectively, these results highlight cross-species plasma biomarkers for SE diagnosis, delineate key cerebellar metabolic mechanisms in SE, and demonstrate therapeutic modulation by human MSC-sEVs.

neuroscience↗

bioRxiv2024

Uncovering microstructural architecture from histology

Mapping the brains fiber network is crucial for understanding its function and malfunction, but resolving nerve trajectories over large fields of view is challenging. Here, we show that computational scattered light imaging (ComSLI) can map fiber networks in histology independent of sample preparation, also in formalin-fixed paraffin-embedded (FFPE) tissues including whole human brain sections. We showcase this method in new and archived, animal and human brain sections, for different sample preparations (in paraffin, deparaffinized, various stains, unstained fresh-frozen). We convert microscopic orientations to microstructure-informed fiber orientation distributions (FODs). Adapting tractography tools from diffusion magnetic resonance imaging (dMRI), we trace axonal trajectories revealing white and gray matter connectivity. These allow us to identify altered microstructure or deficient tracts in demyelinating or neurodegenerating pathology, and to show key advantages over dMRI, polarization microscopy, and structure tensor analysis. Finally, we map fibers in non-brain tissues, including muscle, bone, and blood vessels, unveiling the tissues function. Our cost-effective, versatile approach enables micron-resolution studies of intricate fiber networks across tissues, species, diseases, and sample preparations, offering new dimensions to neuroscientific and biomedical research.

pathology↗

bioRxiv2024

Exposure to HIV alters the composition of maternal microchimeric T cells in infants

Infants exposed to HIV but uninfected (iHEU) display altered cellular immunity and are at increased risk of infection through poorly understood mechanisms. We previously reported that iHEU have lower levels of maternal microchimerism (MMc), maternal cells transferred to the offspring in utero/during breastfeeding. We evaluated MMc levels in T cell subsets in iHEU and HIV unexposed infants (iHU) to determine whether a selective deficiency in MMc may contribute to altered cellular immunity. Across all infants, MMc levels were highest in CD8+ T cells; however, the level of MMc in the CD8 T cell subset was significantly lower in iHEU compared to iHU.

immunology↗

bioRxiv2024

Pre-challenge gut microbial signature predicts RhCMV/SIV vaccine efficacy in rhesus macaques

BackgroundRhCMV/SIV vaccines protect [~]59% of vaccinated rhesus macaques against repeated limiting-dose intra-rectal exposure with highly pathogenic SIVmac239M, but the exact mechanism responsible for the vaccine efficacy is not known. It is becoming evident that complex interactions exist between gut microbiota and the host immune system. Here we aimed to investigate if the rhesus gut microbiome impacts RhCMV/SIV vaccine-induced protection. MethodsThree groups of 15 rhesus macaques naturally pre-exposed to RhCMV were vaccinated with RhCMV/SIV vaccines. Rectal swabs were collected longitudinally both before SIV challenge (after vaccination) and post challenge and were profiled using 16S rRNA based microbiome analysis. ResultsWe identified [~]2,400 16S rRNA amplicon sequence variants (ASVs), representing potential bacterial species/strains. Global gut microbial profiles were strongly associated with each of the three vaccination groups, and all animals tended to maintain consistent profiles throughout the pre-challenge phase. Despite vaccination group differences, using newly developed compositional data analysis techniques we identified a common gut microbial signature predictive of vaccine protection outcome across the three vaccination groups. Part of this microbial signature persisted even after SIV challenge. We also observed a strong correlation between this microbial signature and an early signature derived from whole blood transcriptomes in the same animals. ConclusionsOur findings indicate that changes in gut microbiomes are associated with RhCMV/SIV vaccine-induced protection and early host response to vaccination in rhesus macaques.

microbiology↗

bioRxiv2023

A novel non-invasive method to sample immune cells in the lower female genital tract

T cells in the human female genital tract (FGT)2 are key mediators of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods require a healthcare provider and are expensive, limiting the ability to study these populations longitudinally. To address these challenges, we have developed a method to sample immune cells from the FGT utilizing disposable menstrual discs which are non-invasive, self-applied, and low-cost. To demonstrate reproducibility, we sampled the cervicovaginal fluid (CVF)3 of healthy, reproductive-aged individuals using menstrual discs over three sequential days. CVF was processed for cervicovaginal cells, and high parameter flow cytometry was used to characterize immune populations. We identified large numbers of live, CD45+ leukocytes, as well as distinct populations of T cells and B cells. Within the T cell compartment, activation and suppression status of T cell subsets were consistent with previous studies of the FGT utilizing current approaches, including identification of both tissue resident and migratory populations. In addition, the T cell population structure was highly conserved across days within individuals but divergent across individuals. Our approach to sample immune cells in the FGT with menstrual discs will decrease barriers to participation and empower longitudinal sampling in future research studies.

immunology↗

bioRxiv2021

Wild-type Caenorhabditis elegans Isolates Exhibit Distinct Gene Expression Profiles in Response to Microbial Infection

The soil-dwelling nematode Caenorhabditis elegans serves as a model system to study innate immunity against microbial pathogens. C. elegans have been collected from around the world, where they, presumably, adapted to regional microbial ecologies. Here we use survival assays and RNA- sequencing to better understand how two isolates from disparate climates respond to pathogenic bacteria. We found that, relative to N2 (originally isolated in Bristol, UK), CB4856 (isolated in Hawaii), was more susceptible to the Gram-positive pathogen, Staphylococcus epidermidis, but equally susceptible to Staphylococcus aureus as well as two Gram-negative pathogens, Providencia rettgeri and Pseudomonas aeruginosa. We performed transcriptome analysis of infected worms and found gene- expression profiles were considerably different in an isolate-specific and pathogen-specific manner. We performed GO term analysis to categorize differential gene expression in response to S. epidermidis. In N2, genes that encoded detoxification enzymes and extracellular matrix proteins were significantly enriched, while in CB4856, genes that encoded detoxification enzymes, C-type lectins, and lipid metabolism proteins were enriched, suggesting they have different responses to these bacterial pathogens, despite being the same species. Overall, discerning gene expression signatures in an isolate by pathogen manner can help us to understand the different possibilities for the evolution of immune responses within organisms.

genomics↗

bioRxiv2021

Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here in both murine and human PDA we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through Tumor-Associated Collagen Signatures (TACS), resulting in early dissemination from histologically pre-malignant lesions and continual invasion from well-differentiated disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in novel microfluidics-derived microtissues and in vivo demonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to re-engineer and normalize tumor microenvironments, may have a role not only in also in very early disease but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination. Impact StatementCollagen architectures in the tumor stroma facilitate dissemination of carcinoma cells from the earliest histologically "pre-malignant" lesions and continue to promote disease spread from well-differentiated PDA.

cancer biology↗

bioRxiv2019

Profiling the E. coli Membrane Interactome Captured in Peptidisc Libraries

Protein-correlation-profiling (PCP), in combination with quantitative proteomics, has emerged as a high-throughput method for the rapid identification of dynamic protein complexes in native conditions. While PCP has been successfully applied to soluble proteomes, characterization of the membrane interactome has lagged, partly due to the necessary use of detergents to maintain protein solubility. Here, we apply the peptidisc, a one-size fits all membrane mimetic, for the capture of the Escherichia coli cell envelope proteome and its high-resolution fractionation in the absence of detergent. Analysis of the SILAC-labeled peptidisc library via PCP allows generation of over 4900 possible binary interactions out of >700,000 random associations. Using well-characterized membrane protein systems such as the SecY translocon, the Bam complex and the MetNI transporter, we find our dataset very useful for identifying transient and surprisingly novel protein interactions. For example, we discover a trans-periplasmic super-complex comprising subunits of the Bam and Sec translocons, including membrane-bound chaperones YfgM and PpiD. We identify RcsF and OmpA as bone fide interactors of BamA, and we show that interaction of MetQ with the ABC transporter MetNI depends on its N-terminal lipid anchor. We also discover NlpA as a novel interactor of MetNIQ. Most of these interactions are largely undetected by standard detergent-based purification. Together, the peptidisc workflow applied to the proteomic field is emerging as a promising novel approach to characterize membrane protein interactions under native expression conditions and without genetic manipulation.

biochemistry↗

bioRxiv2018

Generation of tumorigenic porcine pancreatic ductal epithelial cells: toward a large animal model of pancreatic cancer

Background. A large animal model of pancreatic cancer would permit development of diagnostic and interventional technologies not possible in murine models, and also would provide a more biologically-relevant platform for penultimate testing of novel therapies, prior to human testing. Here, we describe our initial studies in the development of an autochthonous, genetically-defined, large animal model of pancreatic cancer, using immunocompetent pigs.\n\nMethods. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs; epithelial origin was confirmed with immunohistochemistry. Three transformed cell lines subsequently were generated from these primary cells using expression of oncogenic KRAS and dominant negative p53, with/without knockdown of p16 and SMAD4. We tested these cell lines using in vitro and in vivo assays of transformation and tumorigenesis.\n\nResults. The transformed cell lines outperformed the primary cells in terms proliferation, population doubling time, soft agar growth, 2D migration, and Matrigel invasion, with the greatest differences observed when all four genes (KRAS, p53, p16, and SMAD4) were targeted. All three transformed cell lines grew tumors when injected subcutaneously in nude mice, demonstrating undifferentiated morphology, mild desmoplasia, and staining for both epithelial and mesenchymal markers. Injection into the pancreas of nude mice resulted in distant metastases, particularly when all four genes were targeted.\n\nConclusions. Tumorigenic porcine pancreatic cell lines were generated. Inclusion of four genetic \"hits\" (KRAS, p53, p16, and SMAD4) appeared to produce the best results in our in vitro and in vivo assays. The next step will be to perform autologous or syngeneic implantation of these cell lines into the pancreas of immunocompetent pigs. We believe that the resultant large animal model of pancreatic cancer could supplement existing murine models, thus improving preclinical research on diagnostic, interventional, and therapeutic technologies.

cancer biology↗

bioRxiv2017

Fluid administration rate for uncontrolled intraabdominal hemorrhage in pigs

BackgroundWe hypothesized that slow crystalloid resuscitation would improve blood loss and hemoglobin compared to a rapid resuscitation during uncontrolled hemorrhage.\n\nMethodsAnesthetized, splenectomized domestic swine underwent hepatic lobar hemitransection. Lactated Ringers was given at 150 or 20 mL/min IV (rapid vs. slow, respectively, N = 12 per group; limit of 100 mL/kg). Vital sign monitoring and serum testing was done for up to 180 min, followed by necropsy.\n\nResultsSurvival was 7 vs. 8 out of 12 subjects, rapid vs. slow respectively (p>0.05). The slow group had a less blood loss (1.6 vs. 2.7 L, respectively) and a higher final hemoglobin concentration (6.0 vs. 3.4 g/dL).\n\nConclusionsUsing a fixed volume of crystalloid resuscitation in this porcine model of uncontrolled intraabdominal hemorrhage, a slow IV infusion rate produced less blood loss and a higher hemoglobin level compared to rapid infusion.

physiology↗