Foodborne Botulism, Canada, 2006-20211.

During 2006-2021, Canada had 55 laboratory-confirmed outbreaks of foodborne botulism, involving 67 cases. The mean annual incidence was 0.01 case/100,000 population. Foodborne botulism in Indigenous communities accounted for 46% of all cases, which is down from 85% of all cases during 1990-2005. Among all cases, 52% were caused by botulinum neurotoxin type E, but types A (24%), B (16%), F (3%), and AB (1%) also occurred; 3% were caused by undetermined serotypes. Four outbreaks resulted from commercial products, including a 2006 international outbreak caused by carrot juice. Hospital data indicated that 78% of patients were transferred to special care units and 70% required mechanical ventilation; 7 deaths were reported. Botulinum neurotoxin type A was associated with much longer hospital stays and more time spent in special care than types B or E. Foodborne botulism often is misdiagnosed. Increased clinician awareness can improve diagnosis, which can aid epidemiologic investigations and patient treatment.

Viable Clostridium botulinum spores not detected in the household dust of major Canadian cities.

Clostridium botulinum causes infant botulism by colonising the intestines and producing botulinum neurotoxin in situ. Previous reports have linked infant botulism cases to C. botulinum spores in household dust, yet the baseline incidence of C. botulinum spores in residential households is currently unknown. Vacuum cleaner dust from 963 households in 13 major Canadian cities was tested for C. botulinum using a novel real-time PCR assay directed against all known subtypes of the botulinum neurotoxin gene. None of the samples tested positive for C. botulinum. Analysis of a random subset of samples by MALDI Biotyper revealed that the most common anaerobic bacterial isolates were of the genus Clostridium and the most common species recovered overall was Clostridium perfringens. Dust that was spiked with C. botulinum spores of each toxin type successfully produced positive real-time PCR reactions. These control experiments indicate that this is a viable method for the detection of C. botulinum spores in household dust. We make several recommendations for future work that may help discover a common environmental source of C. botulinum spores that could lead to effective preventative measures for this rare but deadly childhood disease.

Group-Targeting SERS Screening of Total Benzodiazepines Based on Large-Size (111) Faceted Silver Nanosheets Decorated with Zinc Oxide Nanoparticles.

Rapid, quantitative, and group-targeting detection of total benzodiazepines (BZDs) is critical to create an accurate judgement in emergent medical and forensic settings. Large-size (111) faceted Ag nanosheets decorated with small ZnO nanoparticles were designed as the prominent surface-enhanced Raman scattering substrate, which possessed advantages of specific metal facets and additional charge-transfer (CT) effect from the semiconductor. The vital and bridge role of ZnO in the CT effect was systematically studied via experimental investigations and molecular dynamics simulation, which proves the essentiality of an appropriate ZnO decoration density. Upon determining optimal Ag NS/ZnO hybrids, a calibration curve of estazolam was established with a 0.5 nM detection limit. Based on the obtained curve, group-targeting screening was achieved toward total concentrations of five BZDs (estazolam, oxazepam, alprazolam, triazolam, and lorazepam). Importantly, the total concentrations of BZDs in mice serum were accurately monitored with changing analytical time during the metabolic process, which was in agreement with the tendency measured by liquid chromatography with tandem mass spectrometry.

Selective Synthesis of Monodisperse CoO Nanooctahedra as Catalysts for Electrochemical Water Oxidation.

Thermal decomposition is a promising route for the synthesis of metal oxide nanoparticles because size and morphology can be tuned by minute control of the reaction variables. We synthesized CoO nanooctahedra with diameters of ∼48 nm and a narrow size distribution. Full control over nanoparticle size and morphology could be obtained by controlling the reaction time, surfactant ratio, and reactant concentrations. We show that the particle size does not increase monotonically with time or surfactant concentration but passes through minima or maxima. We unravel the critical role of the surfactants in nucleation and growth and rationalize the observed experimental trends in accordance with simulation experiments. The as-synthesized CoO nanooctahedra exhibit superior electrocatalytic activity with long-term stability during oxygen evolution. The morphology of the CoO particles controls the electrocatalytic reaction through the distinct surface sites involved in the oxygen evolution reaction.

Local Structure and Spectroscopic Properties of Eu3+-Doped BaZrO3.

Pristine and Eu3+-doped BaZrO3 were synthesized via a solid-state reaction method, and the synthesized samples were systematically characterized. X-ray diffraction confirmed the formation of single and pure phases of cubic-structured BaZrO3. Extended X-ray absorption fine structure (EXAFS) spectroscopy revealed the site occupancy of Eu3+ and coordination environment around the different atomic sites. Photoluminescence (PL) excitation and emission spectra revealed the dominant absorption at 275 nm and a broad emission centered at 400 nm due to oxygen vacancies below the conduction band (CB). The PL emission intensity at 597 nm increased with increasing Eu3+ doping concentration; simultaneously, emission from the defect level decreased. This confirmed the efficient energy transfer from oxygen vacancies to Eu3+. Density functional theory was employed to calculate the density of states (DOS) to explain the mechanisms of the PL phenomenon. DOS also showed the presence of impurity states due to Eu3+ doping within the band-gap region. The coincidence of the oxygen vacancy state with Eu f state at the bottom of the CB confirmed the PL energy-transfer mechanisms from the oxygen vacancy to europium. The excited-state lifetime values of the 5D0 state decreased with increasing doping concentration due to the increase of the nonradiative transition rate. The internal quantum efficiency, small excited-state lifetime, and photometric parameters indicated that 3 mol % Eu3+-doped BaZrO3 can be a suitable candidate for the red-light-emitting device applications.

Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-ß. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. SIGNIFICANCE STATEMENT: Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here we detected an age-dependent decline in the expression of aerobic glycolysis enzymes and a concomitant decrease in lactate levels within the frontal cortex of wild-type mice. Improved memory performance in wild-type mice correlated with elevated expression of aerobic glycolysis enzymes. Surprisingly, lactate levels remained elevated with age and increased aerobic glycolysis enzyme expression correlated with poorer memory performance in APP/PS1 mice. These findings suggest that while lactate production is beneficial for memory in the healthy aging brain, it might be detrimental in an Alzheimer's disease context.

Age-dependent metabolic dysregulation in cancer and Alzheimer's disease.

Age is the main risk factor for cancer and neurodegeneration; two radically divergent diseases. Yet selective pressure to meet cellular metabolic needs may provide a common mechanism linking these two disorders. The exclusive use of glycolysis, despite the presence of oxygen, is commonly referred to as aerobic glycolysis and is the primary metabolic pathway of cancer cells. Recent evidence suggests that aerobic glycolysis is also a key regulator of synaptic plasticity in the brain that may positively influence cognition. Elevated aerobic glycolysis is a contributing factor to the development of cancer as increased glycolytic flux plays an important role in the biosynthesis of macromolecules and promotes proliferation. In contrast, decreased aerobic glycolysis in the brain occurs with age and could lead to a loss of cell survival mechanisms that counter pathogenic processes underlying neurodegeneration. In this review we discuss the recent findings from epidemiological studies demonstrating an inverse comorbidity of cancer and Alzheimer's disease. We summarize evidence linking the two diseases through changes in metabolism over the course of normal aging. We discuss the key steps and regulatory mechanisms of aerobic glycolysis and mitochondrial oxidative phosphorylation which could be exploited for the development of novel therapies. In addition, we outline the regulation of aerobic glycolysis at the transcriptional level by HIF-1α and Pin1 and their roles in cancer and neurodegeneration. Finally, we provide a possible explanation for metabolic dysregulation that occurs with age, and how it may be a contributing factor to age-related diseases. Determining how metabolism becomes dysregulated over time could lead to the development of effective interventions for ensuring metabolic homeostasis and healthy aging.

Complete genomes of Clostridium botulinum type B(F) isolates associated with a 1995 foodborne botulism outbreak from commercial pâté reveals a recombination event disrupting the ntnh gene.

Foodborne botulism is a neuroparalytic disease caused by ingestion of foods contaminated with botulinum neurotoxin (BoNT), produced by Clostridium botulinum. In 1995 a husband and wife from Québec, Canada, were hospitalized for several months with prolonged muscle paralysis after ingesting a commercial pâté de campagne. Examination of faecal samples from both patients and the pâté produced viable Group I (proteolytic) C. botulinum type B from each of the three samples. Whole genome sequencing revealed that all three isolates contain identical bont/B5 and bont/F2 genes encoded on a plasmid. Both faecal isolate genomes were identical in chromosome and plasmid length, as well as gene content. The genome of the pâté isolate was nearly identical to that of the faecal isolates with the notable difference of a missing 13-gene insertion on the bont/B5 cluster disrupting the ntnh gene. Examination of the insertion revealed several mobile genetic elements that participate in recombination.

Inactivation of Group I and Group II Clostridium botulinum spores by ultraviolet irradiation in water.

Spores of Clostridium botulinum are widely distributed in the environment, including in foods. Prevention of foodborne botulism relies on the inhibition of spore germination and subsequent growth and toxin production, or the destruction of viable spores in food and beverages. This study examined the lethality of 254 nm UV radiation (UV-C) to spores of Group I and Group II C. botulinum. Spores of C. botulinum were inactivated by UV-C, with doses required for incremental log reduction (D10) values calculated using linear regression ranging from 2.87 to 3.70 mJ/cm2 for Group I strains and 4.46 to 6.15 mJ/cm2 for Group II strains. The measured D10 value for spores of C. sporogenes ATCC 19404 was 8.27 mJ/cm2 indicating it was more resistant than the strains of C. botulinum used in this study. Calculation of dose per log using a Weibull model resulted in higher D10 values of 6.67 to 8.81 mJ/cm2 for Group I strains and 9.24 to 10.7 mJ/cm2 for Group II strains. Spores of C. sporogenes possessed a D10 value of 14.4 mJ/cm2. The higher values for the Weibull model indicate the Weibull model to be more conservative as a result as it factors in the lag prior to inactivation and the tailing observed with very low numbers of survivors. Spores of both Group I and Group II C. botulinum strains tended to form large aggregates, visible with phase contrast microscopy, that resulted in severe tailing. Disruption of aggregates by ultrasonication was necessary to obtain linear destruction curves extending beyond 5 log reduction. All strains from Group I and Group II required <55 mJ/cm2 to achieve 5 log inactivation. The strain of C. sporogenes used in this work can therefore be a conservative non-pathogenic surrogate, having higher UV-C resistance than the C. botulinum strains used in this study. Overall, this study is the first detailed study to demonstrate UV-C as an effective treatment method to inactivate C. botulinum spores in a suspending medium. In addition, the study paves the way for further studies towards the applications of this technology to inactivate C. botulinum spores in beverages or other liquids.

Early postnatal defects in neurogenesis in the 3xTg mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to dementia. The hippocampus, which is one of the sites where neural stem cells reside and new neurons are born, exhibits the most significant neuronal loss in AD. A decline in adult neurogenesis has been described in several animal models of AD. However, the age at which this defect first appears remains unknown. To determine at which stage, from birth to adulthood, the neurogenic deficits are found in AD, we used the triple transgenic mouse model of AD (3xTg). We show that defects in neurogenesis are present as early as postnatal stages, well before the onset of any neuropathology or behavioral deficits. We also show that 3xTg mice have significantly fewer neural stem/progenitor cells, with reduced proliferation and decreased numbers of newborn neurons at postnatal stages, consistent with reduced volumes of hippocampal structures. To determine whether there are early changes in the molecular signatures of neural stem/progenitor cells, we perform bulk RNA-seq on cells sorted directly from the hippocampus. We show significant changes in the gene expression profiles at one month of age, including genes of the Notch and Wnt pathways. These findings reveal impairments in neurogenesis very early in the 3xTg AD model, which provides new opportunities for early diagnosis and therapeutic interventions to prevent neurodegeneration in AD.

Adult Intestinal Toxemia Botulism.

Intoxication with botulinum neurotoxin can occur through various routes. Foodborne botulism results after consumption of food in which botulinum neurotoxin-producing clostridia (i.e., Clostridium botulinum or strains of Clostridiumbutyricum type E or Clostridiumbaratii type F) have replicated and produced botulinum neurotoxin. Infection of a wound with C. botulinum and in situ production of botulinum neurotoxin leads to wound botulism. Colonization of the intestine by neurotoxigenic clostridia, with consequent production of botulinum toxin in the intestine, leads to intestinal toxemia botulism. When this occurs in an infant, it is referred to as infant botulism, whereas in adults or children over 1 year of age, it is intestinal colonization botulism. Predisposing factors for intestinal colonization in children or adults include previous bowel or gastric surgery, anatomical bowel abnormalities, Crohn's disease, inflammatory bowel disease, antimicrobial therapy, or foodborne botulism. Intestinal colonization botulism is confirmed by detection of botulinum toxin in serum and/or stool, or isolation of neurotoxigenic clostridia from the stool, without finding a toxic food. Shedding of neurotoxigenic clostridia in the stool may occur for a period of several weeks. Adult intestinal botulism occurs as isolated cases, and may go undiagnosed, contributing to the low reported incidence of this rare disease.

Simple Protocol for Distinguishing Drug-induced Effects on Spatial Memory Acquisition, Consolidation and Retrieval in Mice Using the Morris Water Maze.

The Morris water maze (MWM) is one of the most commonly used tests for assessing spatial learning and memory in mice. While the MWM is highly amenable to testing the effects of memory modifying drugs, most studies do not consider the timing or duration of drug exposure when conducting the MWM assay; factors that can strongly influence the effect of the drug on different stages of memory and interfere with data interpretation. Herein we describe a MWM protocol which offers the advantage of distinguishing the impact of a fast acting intraperitoneally (IP) injected drug on the different stages of spatial memory: acquisition, consolidation, and retrieval. Mice initially undergo habituation to both the MWM apparatus and IP injection procedure over the course of three days. For assessing the effect of a drug on memory acquisition, mice are injected with the drug prior to training sessions over four consecutive days, where mice learn to find an escape platform in a circular water tank using distal spatial cues. To determine the effect of the drug on memory consolidation, mice are injected with the drug immediately after each training session. For testing the effect of a drug on memory retrieval, mice receive mock IP injections on each training day and the drug is IP injected only once, prior to a probe trial, where mice attempt to locate the platform following its removal from the tank. This protocol provides a simple strategy for distinguishing the effect(s) of a CNS acting drug on the different stages of memory.

Aerobic Glycolysis Is Required for Spatial Memory Acquisition But Not Memory Retrieval in Mice.

The consolidation of newly formed memories and their retrieval are energetically demanding processes. Aerobic glycolysis (AG), also known as the Warburg effect, consists of the production of lactate from glucose in the presence of oxygen. The astrocyte neuron lactate shuttle hypothesis posits that astrocytes process glucose by AG to generate lactate, which is used as a fuel source within neurons to maintain synaptic activity. Studies in mice have demonstrated that lactate transport between astrocytes and neurons is required for long-term memory formation, yet the role of lactate production in memory acquisition and retrieval has not previously been explored. Here, we examined the effect of dichloroacetate (DCA), a chemical inhibitor of lactate production, on spatial learning and memory in mice using the Morris water maze (MWM). In vivo hyperpolarized 13C-pyruvate magnetic resonance spectroscopy revealed decreased conversion of pyruvate to lactate in the mouse brain following DCA administration, concomitant with a reduction in the phosphorylation of pyruvate dehydrogenase. DCA exposure before each training session in the MWM impaired learning, which subsequently resulted in impaired memory during the probe trial. In contrast, mice that underwent training without DCA exposure, but received a single DCA injection before the probe trial exhibited normal memory. Our findings indicate that AG plays a key role during memory acquisition but is less important for the retrieval of established memories. Thus, the activation of AG may be important for learning-dependent synaptic plasticity rather than the activation of signaling cascades required for memory retrieval.

p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity.

A key pathological feature of Alzheimer's disease (AD) is the accumulation of the neurotoxic amyloid beta (Aß) peptide within the brains of affected individuals. Previous studies have shown that neuronal cells selected for resistance to Aß toxicity display a metabolic shift from mitochondrial-dependent oxidative phosphorylation (OXPHOS) to aerobic glycolysis to meet their energy needs. The Src homology/collagen (Shc) adaptor protein p66Shc is a key regulator of mitochondrial function, ROS production and aging. Moreover, increased expression and activation of p66Shc promotes a shift in the cellular metabolic state from aerobic glycolysis to OXPHOS in cancer cells. Here we evaluated the hypothesis that activation of p66Shc in CNS cells promotes both increased OXPHOS and enhanced sensitivity to Aß toxicity. The effect of altered p66Shc expression on metabolic activity was assessed in rodent HT22 and B12 cell lines of neuronal and glial origin respectively. Overexpression of p66Shc repressed glycolytic enzyme expression and increased both mitochondrial electron transport chain activity and ROS levels in HT22 cells. The opposite effect was observed when endogenous p66Shc expression was knocked down in B12 cells. Moreover, p66Shc activation in both cell lines increased their sensitivity to Aß toxicity. Our findings indicate that expression and activation of p66Shc renders CNS cells more sensitive to Aß toxicity by promoting mitochondrial OXPHOS and ROS production while repressing aerobic glycolysis. Thus, p66Shc may represent a potential therapeutically relevant target for the treatment of AD.

Use and limitations of magnetic resonance phase-contrast assessment of coronary flow reserve in a model of collateral dependence.

Phase-contrast magnetic resonance imaging (PC-MRI) is useful for assessing coronary artery flow reserves (CFR) in man and acute animal models with intermediate coronary lesions. The present study examines the use of PC-MRI for assessing CFR in a model with critical stenosis and collateral dependence. PC-MRI quantitative flow measurements from the proximal left anterior descending (LAD) and left circumflex (LCX) coronary arteries were compared with myocardial tissue perfusion reserve measurements (microsphere techniques) after placement of a 2.25-mm ameroid constrictor on the proximal LCX in a porcine model; measurements were obtained at implantation (n = 4) and at 3 to 4 weeks (n = 4) and 6 weeks (n = 5) postimplantation. CFR is defined as the ratio of maximal hyperemic flow to baseline flow. Hyperemia was induced using intravenous adenosine (140 mg/kg/min). Collateral dependence in the LCX distri bution was evidenced by angiographic findings of critical stenosis with minimal myocardial histological changes and normal baseline myocardial perfusion (microsphere techniques). In this setting, PC-MRI CFR was correlated with microsphere measures of perfusion reserve. Collateral dependence was confirmed by Evan's blue dye injection. This study provides angiographic, myocardial perfusion, and histological correlates associated with PC-MRI epicardial CFR changes during chronic, progressive coronary artery constriction. It also demonstrates the disparity between epicardial and myocardial measures of coronary flow reserve with collateral dependence and the caveats for PC-MRI use in models of progressive coronary constriction.

Requisite role for Nck adaptors in cardiovascular development, endothelial-to-mesenchymal transition, and directed cell migration.

Development of the cardiovascular system is critically dependent on the ability of endothelial cells (ECs) to reorganize their intracellular actin architecture to facilitate migration, adhesion, and morphogenesis. Nck family cytoskeletal adaptors function as key mediators of actin dynamics in numerous cell types, though their role in EC biology remains largely unexplored. Here, we demonstrate an essential requirement for Nck within ECs. Mouse embryos lacking endothelial Nck1/2 expression develop extensive angiogenic defects that result in lethality at about embryonic day 10. Mutant embryos show immature vascular networks, with decreased vessel branching, aberrant perivascular cell recruitment, and reduced cardiac trabeculation. Strikingly, embryos deficient in endothelial Nck also fail to undergo the endothelial-to-mesenchymal transition (EnMT) required for cardiac valve morphogenesis, with loss of Nck disrupting expression of major EnMT markers, as well as suppressing mesenchymal outgrowth. Furthermore, we show that Nck-null ECs are unable to migrate downstream of vascular endothelial growth factor and angiopoietin-1, and they exhibit profound perturbations in cytoskeletal patterning, with disorganized cellular projections, impaired focal adhesion turnover, and disrupted actin-based signaling. Our collective findings thereby reveal a crucial role for Nck as a master regulator within the endothelium to control actin cytoskeleton organization, vascular network remodeling, and EnMT during cardiovascular development.

Carotid redo surgery: both safe and durable.

AIM: To examine the outcomes and complications of surgery for recurrent carotid stenosis. METHODS: From 1974 to 2000, 1922 carotid endarterectomies were performed in our unit. A retrospective cohort analysis of these records identified 24 patients (1.2%) who underwent surgery for recurrent stenosis. RESULTS: There were 13 men and 11 women in the group. Median follow up was 7.2 years (interquartile range 4.4-12.4 years). The indication for redo surgery was either symptomatic severe (80-99%) or moderate (50-79%) restenosis, or severe asymptomatic (80-99%) restenosis. Repair was performed by patch angioplasty (88%), endarterectomy alone (8%) or interposition grafting (4%). Within the 30 day perioperative period there were no deaths, no strokes (major or minor), or significant cardiac morbidity. One patient (4%) developed a permanent spinal accessory nerve deficit. Another patient (4%) required further re-intervention for recurrent disease. CONCLUSIONS: Very low surgical morbidity and mortality was achieved in our unit by implementing a policy of selective re-intervention for carotid restenosis. Redo carotid endarterectomy can therefore be recommended as having no greater morbidity than primary carotid endarterectomy. Carotid angioplasty and stenting are not recommended as a routine alternative treatment.

Reevaluating Metabolism in Alzheimer's Disease from the Perspective of the Astrocyte-Neuron Lactate Shuttle Model.

The conventional view of central nervous system (CNS) metabolism is based on the assumption that glucose is the main fuel source for active neurons and is processed in an oxidative manner. However, since the early 1990s research has challenged the idea that the energy needs of nerve cells are met exclusively by glucose and oxidative metabolism. This alternative view of glucose utilization contends that astrocytes metabolize glucose to lactate, which is then released and taken up by nearby neurons and used as a fuel source, commonly known as the astrocyte-neuron lactate shuttle (ANLS) model. Once thought of as a waste metabolite, lactate has emerged as a central player in the maintenance of neuronal function and long-term memory. Decreased neuronal metabolism has traditionally been viewed as a hallmark feature of Alzheimer's disease (AD). However, a more complex picture of CNS metabolism is emerging that may provide valuable insight into the pathophysiological changes that occur during AD and other neurodegenerative diseases. This review will examine the ANLS model and present recent evidence highlighting the critical role that lactate plays in neuronal survival and memory. Moreover, the role of glucose and lactate metabolism in AD will be re-evaluated from the perspective of the ANLS.

Damage control management of experimental grade 5 renal injuries: further evaluation of FloSeal gelatin matrix.

BACKGROUND: We developed a porcine grade 5 renal laceration damage control model to evaluate the hemostatic efficacy of FloSeal gelatin matrix (Baxter Healthcare, Corp., Deerfield, Ill). METHODS: Ten commercial swine underwent celiotomy, contralateral nephrectomy, and cooling to 32 degrees C after a well-established hypothermia protocol to simulate a damage control scenario. Following prospective randomization, a complex grade 5 renal injury was uniformly produced on the remaining kidney. Control animals (group 1, n = 5) were treated with direct manual compression with a gelatin sponge. Experimental animals (group 2, n = 5) were treated by application of FloSeal gelatin matrix followed by direct compression with a gelatin sponge. Operative blood loss and efficacy of hemostasis were compared. Creatinine levels were obtained daily until postoperative day 7. Abdominal computed tomography was performed at 10 days. RESULTS: Use of FloSeal gelatin matrix hemostatic sealant resulted in significantly less mean blood loss than gelatin sponge bolster compression alone (202.4 mL vs. 540.4 mL, respectively, p = 0.016). Hemostasis was complete in 60% (three out of five) of experimental animals after 2 minutes, but was incomplete in all control animals. After an initial increase, serum creatinine approached baseline by postoperative day 7 in all animals. Axial imaging 10 days postoperatively revealed no evidence of significant delayed perirenal hemorrhage. CONCLUSIONS: FloSeal gelatin matrix performed well as a rapidly deployable, effective hemostatic agent in a hypothermic grade 5 renal injury damage control model. The absence of delayed bleeding and nephrotoxicity suggests a possible increased role for FloSeal in the treatment of devastating renal injuries in damage control surgery.