Acne vulgaris and risk of depression and anxiety: A meta-analytic review.

BACKGROUND: Several studies have shown an association of acne vulgaris with depression and anxiety, but a quantitative review has not yet been conducted. OBJECTIVE: We sought to conduct a systematic review and meta-analysis that elucidates the association of acne vulgaris with depression and anxiety. METHODS: A systematic review and meta-analysis of literature published before October 1, 2019 from the PubMed, PsycINFO, MEDLINE, and Cochrane databases was conducted. We used a metaanalytic approach to perform a random effects analysis comparing individuals with and without acne. Subgroup analyses between studies included age, study setting, and geographic region. RESULTS: Forty-two studies were included. We found a significant association of acne vulgaris with depression (r = 0.22 [95% confidence interval 0.17-0.26, P < .00001]) and anxiety (r = 0.25 [95% confidence interval 0.19-0.31, P < .00001]). Subgroup analyses and comparisons showed moderating influences based on factors including age, study setting, and geographic region. LIMITATIONS: Inconsistency between publications regarding acne and outcome ascertainment, data reporting, and studies with no control group posed considerable barriers to synthesizing all available published literature. CONCLUSIONS: Because of an increased risk for depression and anxiety, clinicians should pursue aggressive treatment of acne and consider psychiatric screening or referrals.

Clinical Characteristics of Pediatric Patients With Carbon Monoxide Poisoning.

OBJECTIVES: Carbon monoxide (CO) poisoning is a common and deadly form of poisoning that is often treated with hyperbaric oxygen. The characteristics of children exposed to CO and then treated with hyperbaric oxygen have not been delineated. The purpose of this study was to describe the clinical characteristics of children treated with hyperbaric oxygen therapy for CO poisoning at a regional hyperbaric referral center. METHODS: The study is based on a retrospective review of data extracted from the medical records of children (age <19 years) who were referred to our center for hyperbaric oxygen therapy for CO poisoning between 2008 and 2013. Inferential analyses were used to compare demographic characteristics, serum carboxyhemoglobin (COHb) levels, and presenting symptoms. RESULTS: Forty-seven children met our study criteria. Their mean age was 8.9 years, and their mean COHb level was 14.3% (range, 3.4%-30.1%). Severity of symptoms did not correlate with serum COHb levels; however, neurologic symptoms at presentation were more common in patients with a COHb level greater than 25%. There was a correlation between increasing age and higher COHb levels and between COHb and lactate levels. CONCLUSIONS: Our retrospective review of patients' records showed no correlation of serum COHb levels with symptoms on presentation; however, a correlation was found between increasing age and COHb level as well as lactate level and COHb level.

Reduced perineuronal net expression in Fmr1 KO mice auditory cortex and amygdala is linked to impaired fear-associated memory.

Fragile X Syndrome (FXS) is a leading cause of heritable intellectual disability and autism. Humans with FXS show anxiety, sensory hypersensitivity and impaired learning. The mechanisms of learning impairments can be studied in the mouse model of FXS, the Fmr1 KO mouse, using tone-associated fear memory paradigms. Our previous study reported impaired development of parvalbumin (PV) positive interneurons and perineuronal nets (PNN) in the auditory cortex of Fmr1 KO mice. A recent study suggested PNN dynamics in the auditory cortex following tone-shock association is necessary for fear expression. Together these data suggest that abnormal PNN regulation may underlie tone-fear association learning deficits in Fmr1 KO mice. We tested this hypothesis by quantifying PV and PNN expression in the amygdala, hippocampus and auditory cortex of Fmr1 KO mice following fear conditioning. We found impaired tone-associated memory formation in Fmr1 KO mice. This was paralleled by impaired learning-associated regulation of PNNs in the superficial layers of auditory cortex in Fmr1 KO mice. PV cell density decreased in the auditory cortex in response to fear conditioning in both WT and Fmr1 KO mice. Learning-induced increase of PV expression in the CA3 hippocampus was only observed in WT mice. We also found reduced PNN density in the amygdala and auditory cortex of Fmr1 KO mice in all conditions, as well as reduced PNN intensity in CA2 hippocampus. There was a positive correlation between tone-associated memory and PNN density in the amygdala and auditory cortex, consistent with a tone-association deficit. Altogether our studies suggest a link between impaired PV and PNN regulation within specific regions of the fear conditioning circuit and impaired tone memory formation in Fmr1 KO mice.

Carbon monoxide and ST-elevation myocardial infarction: case reports.

We describe two cases of myocardial infarction with ST-segment elevation on electrocardiogram associated with carbon monoxide (CO) poisoning, a condition rarely reported in the literature. The first was a 62-year-old woman who experienced chest pain in the emergency department (ED) while being assessed for exposure to carbon monoxide in her home. The second was an 80-year-old man who fainted at home and was found to have ST elevation during the ED workup. After hospitalization, he returned home and soon thereafter had difficulty walking and speaking. The responding paramedics detected a very high CO level in the home. Both patients received hyperbaric oxygen therapy within the first several hours of presentation. For this combination of conditions, it is difficult to derive evidence-based management recommendations, given the paucity of cases reported to date. We conclude that rapid consultation with interventional cardiology and consideration of angioplasty or stenting are appropriate, especially when electrocardiographic findings and echocardiography point to a specific coronary distribution. Hyperbaric oxygen therapy might have a role in the treatment, based on its effects on myocardial ischemia and injury in other models.

Transradial Renal Angioplasty and Stent Placement for Systemic Hypertension Caused by Severe Unilateral Renovascular Stenosis.

Percutaneous transluminal angioplasty and stent placement for renovascular hypertension is a recognized albeit seldom used therapy. We present a case of severe renovascular hypertension, due to renal artery atherosclerosis, treated successfully with stent placement via the radial artery access approach.

Selective publication of antidepressant trials and its influence on apparent efficacy.

BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients.

Air-Evacuation-Relevant Hypobaria Following Traumatic Brain Injury Plus Hemorrhagic Shock in Rats Increases Mortality and Injury to the Gut, Lungs, and Kidneys.

ABSTRACT: Rats exposed to hypobaria equivalent to what occurs during aeromedical evacuation within a few days after isolated traumatic brain injury exhibit greater neurologic injury than those remaining at sea level. Moreover, administration of excessive supplemental O2 during hypobaria further exacerbates brain injury. This study tested the hypothesis that exposure of rats to hypobaria following controlled cortical impact (CCI)-induced brain injury plus mild hemorrhagic shock worsens multiple organ inflammation and associated mortality. In this study, at 24 h after CCI plus hemorrhagic shock, rats were exposed to either normobaria (sea level) or hypobaria (=8,000 ft altitude) for 6 h under normoxic or hyperoxic conditions. Injured rats exhibited mortality ranging from 30% for those maintained under normobaria and normoxia to 60% for those exposed to 6 h under hypobaric and hyperoxia. Lung histopathology and neutrophil infiltration at 2 days postinjury were exacerbated by hypobaria and hyperoxia. Gut and kidney inflammation at 30 days postinjury were also worsened by hypobaric hyperoxia. In conclusion, exposure of rats after brain injury and hemorrhagic shock to hypobaria or hyperoxia results in increased mortality. Based on gut, lung, and kidney histopathology at 2 to 30 days postinjury, increased mortality is consistent with multi-organ inflammation. These findings support epidemiological studies indicating that increasing aircraft cabin pressures to 4,000 ft altitude (compared with standard 8,000 ft) and limiting excessive oxygen administration will decrease critical complications during and following aeromedical transport.

Transcriptional activation of antioxidant gene expression by Nrf2 protects against mitochondrial dysfunction and neuronal death associated with acute and chronic neurodegeneration.

Mitochondria are both a primary source of reactive oxygen species (ROS) and a sensitive target of oxidative stress; damage to mitochondria can result in bioenergetic dysfunction and both necrotic and apoptotic cell death. These relationships between mitochondria and cell death are particularly strong in both acute and chronic neurodegenerative disorders. ROS levels are affected by both the production of superoxide and its toxic metabolites and by antioxidant defense mechanisms. Mitochondrial antioxidant activities include superoxide dismutase 2, glutathione peroxidase and reductase, and intramitochondrial glutathione. When intracellular conditions disrupt the homeostatic balance between ROS production and detoxification, a net increase in ROS and an oxidized shift in cellular redox state ensues. Cells respond to this imbalance by increasing the expression of genes that code for proteins that protect against oxidative stress and inhibit cytotoxic oxidation of proteins, DNA, and lipids. If, however, the genomic response to mitochondrial oxidative stress is insufficient to maintain homeostasis, mitochondrial bioenergetic dysfunction and release of pro-apoptotic mitochondrial proteins into the cytosol initiate a variety of cell death pathways, ultimately resulting in potentially lethal damage to vital organs, including the brain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a translational activating protein that enters the nucleus in response to oxidative stress, resulting in increased expression of numerous cytoprotective genes, including genes coding for mitochondrial and non-mitochondrial antioxidant proteins. Many experimental and some FDA-approved drugs promote this process. Since mitochondria are targets of ROS, it follows that protection against mitochondrial oxidative stress by the Nrf2 pathway of gene expression contributes to neuroprotection by these drugs. This document reviews the evidence that Nrf2 activation increases mitochondrial antioxidants, thereby protecting mitochondria from dysfunction and protecting neural cells from damage and death. New experimental results are provided demonstrating that post-ischemic administration of the Nrf2 activator sulforaphane protects against hippocampal neuronal death and neurologic injury in a clinically-relevant animal model of cardiac arrest and resuscitation.

Lineup administrator influences on eyewitness identification decisions.

The present research examines how a lineup administrator may influence eyewitness identification decisions through different forms of influence, after providing the witness with standard, unbiased instructions. Participant-witnesses viewed a staged crime and were later shown a target-present or target-absent lineup. The lineup administrators either remained silent while the witness examined the lineup, made ostensibly cautionary statements to the witness, or prompted the witness to identify the person in the lineup who seemed most similar to the perpetrator. These two forms of influence, denoted as subtle-influence and similarity-influence conditions, led to different patterns of identification results. Results for the similarity-influence condition were generally consistent with criterion shift and relative judgment models of eyewitness decision making. Results for the subtle-influence condition, however, cannot be explained by alterations in the decision rule. A weighted matching model is outlined to explain results from the subtle-influence condition. Witnesses seemed generally unaware of the attempts by the lineup administrator to influence their decision, although some noted it, and the probative value of suspect identifications was lower for those who did note it. Implications for theory and policy are discussed.

Oximetry-Guided normoxic resuscitation following canine cardiac arrest reduces cerebellar Purkinje neuronal damage.

BACKGROUND: Animal studies indicate that maintaining physiologic O2 levels (normoxia) immediately after restoration of spontaneous circulation (ROSC) from cardiac arrest (CA) results in less hippocampal neuronal death compared to animals ventilated with 100% O2. This study tested the hypothesis that beneficial effects of avoiding hyperoxia following CA are apparent in the cerebellum and therefore not limited to one brain region. METHODS: Adult beagles were anesthetized and mechanically ventilated. Ventricular fibrillation CA was induced by electrical myocardial stimulation and cessation of ventilation. Ten min later, dogs were ventilated with 100% O2 and resuscitated using 3 min of open chest CPR followed by defibrillation. Dogs were ventilated for 1 h with either 100% O2 or with O2 titrated rapidly to maintain hemoglobin O2 saturation at 94-96%. FiO2 was adjusted in both groups between one and 24 h post-arrest to maintain normoxic PaO2 of 80-120 mm Hg. Following 24 h critical care, dogs were euthanized and cerebellum analyzed for histochemical measures of neuronal damage and inflammation. RESULTS AND CONCLUSIONS: Hyperoxic resuscitation increased the number of injured Purkinje cells by 278% and the number of activated microglia/macrophages by 18% compared to normoxic resuscitation. These results indicate that normoxic resuscitation promotes favorable histopathologic outcomes in the cerebellum (in addition to hippocampus) following CA/ROSC. These findings emphasize the importance of avoiding unnecessary hyperoxia following CA/ROSC.

Physician and patient communication training in primary care: effects on participation and satisfaction.

OBJECTIVE: To assess the effects of a communication skills training program for physicians and patients. DESIGN: A randomized experiment to improve physician communication skills was assessed 1 and 6 months after a training intervention; patient training to be active participants was assessed after 1 month. Across three primary medical care settings, 156 physicians treating 2,196 patients were randomly assigned to control group or one of three conditions (physician, patient, or both trained). MAIN OUTCOME MEASURES: Patient satisfaction and perceptions of choice, decision-making, information, and lifestyle counseling; physicians' satisfaction and stress; and global ratings of the communication process. RESULTS: The following significant (p < .05) effects emerged: physician training improved patients' satisfaction with information and overall care; increased willingness to recommend the physician; increased physicians' counseling (as reported by patients) about weight loss, exercise, and quitting smoking and alcohol; increased physician satisfaction with physical exam detail; increased independent ratings of physicians' sensitive, connected communication with their patients, and decreased physician satisfaction with interpersonal aspects of professional life. Patient training improved physicians' satisfaction with data collection; if only physician or patient was trained, physician stress increased and physician satisfaction decreased. CONCLUSION: Implications for improving physician-patient relationship outcomes through communication skills training are discussed.

Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria.

At abnormally elevated levels of intracellular Ca2+, mitochondrial Ca2+ uptake may compromise mitochondrial electron transport activities and trigger membrane permeability changes that allow for release of cytochrome c and other mitochondrial apoptotic proteins into the cytosol. In this study, a clinically relevant canine cardiac arrest model was used to assess the effects of global cerebral ischemia and reperfusion on mitochondrial Ca2+ uptake capacity, Ca2+ uptake-mediated inhibition of respiration, and Ca2+-induced cytochrome c release, as measured in vitro in a K+-based medium in the presence of Mg2+, ATP, and NADH-linked oxidizable substrates. Maximum Ca2+ uptake by frontal cortex mitochondria was significantly lower following 10 min cardiac arrest compared to non-ischemic controls. Mitochondria from ischemic brains were also more sensitive to the respiratory inhibition associated with accumulation of large levels of Ca2+. Cytochrome c was released from brain mitochondria in vitro in a Ca2+-dose-dependent manner and was more pronounced following both 10 min of ischemia alone and following 24 h reperfusion, in comparison to mitochondria from non-ischemic Shams. These effects of ischemia and reperfusion on brain mitochondria could compromise intracellular Ca2+ homeostasis, decrease aerobic and increase anaerobic cerebral energy metabolism, and potentiate the cytochrome c-dependent induction of apoptosis, when re-oxygenated mitochondria are exposed to abnormally high levels of intracellular Ca2+.

ADRA2B deletion variant and enhanced cognitive processing of emotional information: A meta-analytical review.

This meta-analytical review examines whether a deletion variant in ADRA2B, a gene that encodes α2B adrenoceptor in the regulation of norepinephrine availability, influences cognitive processing of emotional information in human observers. Using a multilevel modeling approach, this meta-analysis of 16 published studies with a total of 2752 participants showed that ADRA2B deletion variant was significantly associated with enhanced perceptual and cognitive task performance for emotional stimuli. In contrast, this genetic effect did not manifest in overall task performance when non-emotional content was used. Furthermore, various study-level factors, such as targeted cognitive processes (memory vs. attention/perception) and task procedures (recall vs. recognition), could moderate the size of this genetic effect. Overall, with increased statistical power and standardized analytical procedures, this meta-analysis has established the contributions of ADRA2B to the interactions between emotion and cognition, adding to the growing literature on individual differences in attention, perception, and memory for emotional information in the general population.

Hyperoxic reperfusion after global ischemia decreases hippocampal energy metabolism.

BACKGROUND AND PURPOSE: Previous reports indicate that compared with normoxia, 100% ventilatory O(2) during early reperfusion after global cerebral ischemia decreases hippocampal pyruvate dehydrogenase activity and increases neuronal death. However, current standards of care after cardiac arrest encourage the use of 100% O(2) during resuscitation and for an undefined period thereafter. Using a clinically relevant canine cardiac arrest model, in this study we tested the hypothesis that hyperoxic reperfusion decreases hippocampal glucose metabolism and glutamate synthesis. METHODS: After 10 minutes of cardiac arrest, animals were resuscitated and ventilated for 1 hour with 100% O(2) (hyperoxic) or 21% to 30% O(2) (normoxic). At 30 minutes reperfusion, [1-(13)C]glucose was infused, and at 2 hours, brains were rapidly removed and frozen. Extracted metabolites were analyzed by (13)C nuclear magnetic resonance spectroscopy. RESULTS: Compared with nonischemic controls, the hippocampi from hyperoxic animals had elevated levels of unmetabolized (13)C-glucose and decreased incorporation of (13)C into all isotope isomers of glutamate. These findings indicate impaired neuronal metabolism via the pyruvate dehydrogenase pathway for carbon entry into the tricarboxylic acid cycle and impaired glucose metabolism via the astrocytic pyruvate carboxylase pathway. No differences were observed in the cortex, indicating that the hippocampus is more vulnerable to metabolic changes induced by hyperoxic reperfusion. CONCLUSIONS: These results represent the first direct evidence that hyperoxia after cardiac arrest impairs hippocampal oxidative energy metabolism in the brain and challenge the rationale for using excessively high resuscitative ventilatory O(2).

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study.

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.

Ultrasound-diagnosed cardiac tamponade after blunt abdominal trauma-treated with emergent thoracotomy.

Ultrasound imaging enhances the physician's ability to evaluate, diagnose, and treat emergency department (ED) patients. Because ultrasound imaging is often time-dependent in the acutely ill or injured patient, the emergency physician is in an ideal position to use this technology. Focused ultrasound examinations provide immediate information and can answer specific questions about the patient's physical condition. We report a case in which blunt trauma to the abdomen and pre-existing pericardial fluid, due to human immunodeficiency virus (HIV), caused pericardial tamponade, diagnosed by bedside ultrasonography, and subsequent cardiac arrest. An ED thoracotomy released this tamponade, and spontaneous cardiac activity returned. The indications for and efficacy of ED thoracotomy have been debated for many years. Multiple studies have shown that patients with isolated penetrating chest trauma have the best outcome and that patients with blunt trauma without signs of life at the scene or in the ED have the poorest. We demonstrate the importance of ultrasound use by emergency physicians to assess trauma patients with pulseless electrical activity and suggest that in specific clinical situations after blunt trauma, an ED thoracotomy can be life saving.

Evaluation of a novel immunomodulator composed of human chorionic gonadotropin and bacillus Calmette-Guerin for treatment of canine mast cell tumors in clinically affected dogs.

OBJECTIVE: To evaluate safety and efficacy of LDI-100, a preparation containing human chorionic gonadotropin (hCG) and bacillus Calmette-Guerin (BCG), in the treatment of dogs with mast cell tumors and to compare results with those from a control group receiving single-agent vinblastine. ANIMALS: 95 dogs with measurable grade II or III mast cell tumors. PROCEDURES: Dogs were randomized to receive either LDI-100 (1.35 ng of BCG and 2 units of hCG, SC, q 24 h) or vinblastine (2 mg/m(2), IV, q 1 wk) for 6 weeks. Tumors were measured at baseline and day 42, and dogs were monitored for signs of toxicosis. Clinical performance scores were recorded at each visit. Differences in host factors (sex, weight, and age), clinical performance score, tumor response, and adverse events were analyzed. RESULTS: 46 dogs received LDI-100, and 49 dogs received vinblastine. No significant differences were found between the 2 treatment groups with regard to host factors or clinical performance score. Tumor response (>or=50% reduction) rates were similar between the LDI-100 and vinblastine group (28.6% and 11.7%, respectively). Dogs in the LDI-100 group had significantly less neutropenia than the vinblastine group. CONCLUSIONS AND CLINICAL RELEVANCE: hCG and BCG have immunomodulatory and antitumor effects against a variety of malignancies in humans and dogs. In this study, LDI-100 provided clinical responses comparable to single-agent vinblastine chemotherapy but without myelosuppression. LDI-100 is a promising new agent that should be further investigated for multimodality therapy of mast cell tumors in dogs.

Inhaler syncope.

Syncope can result from certain activities that trigger an exaggerated physiological response in susceptible individuals; examples include cough, laugh, and micturition syncope. We report a novel cause for syncope, that due to reflex bradycardia and asystole produced by the use of asthma inhalers. We discuss the possible mechanisms for this effect and briefly review other breathing-related causes of bradycardia.

Aeromedical evacuation-relevant hypobaria worsens axonal and neurologic injury in rats after underbody blast-induced hyperacceleration.

BACKGROUND: Occupants of military vehicles targeted by explosive devices often suffer from traumatic brain injury (TBI) and are typically transported by the aeromedical evacuation (AE) system to a military medical center within a few days. This study tested the hypothesis that exposure of rats to AE-relevant hypobaria worsens cerebral axonal injury and neurologic impairment caused by underbody blasts. METHODS: Anesthetized adult male rats were secured within cylinders attached to a metal plate, simulating the hull of an armored vehicle. An explosive located under the plate was detonated, resulting in a peak vertical acceleration force on the plate and occupant rats of 100G. Rats remained under normobaria or were exposed to hypobaria equal to 8,000 feet in an altitude chamber for 6 hours, starting at 6 hours to 6 days after blast. At 7 days, rats were tested for vestibulomotor function using the balance beam walking task and euthanized by perfusion. The brains were then analyzed for axonal fiber injury. RESULTS: The number of internal capsule silver-stained axonal fibers was greater in animals exposed to 100G blast than in shams. Animals exposed to hypobaria starting at 6 hours to 6 days after blast exhibited more silver-stained fibers than those not exposed to hypobaria. Rats exposed to 100% oxygen (O2) during hypobaria at 24 hours postblast displayed greater silver staining and more balance beam foot-faults, in comparison with rats exposed to hypobaria under 21% O2. CONCLUSION: Exposure of rats to blast-induced acceleration of 100G increases cerebral axonal injury, which is significantly exacerbated by exposure to hypobaria as early as 6 hours and as late as 6 days postblast. Rats exposed to underbody blasts and then to hypobaria under 100% O2 exhibit increased axonal damage and impaired motor function compared to those subjected to blast and hypobaria under 21% O2. These findings raise concern about the effects of AE-related hypobaria on TBI victims, the timing of AE after TBI, and whether these effects can be mitigated by supplemental oxygen.