2,342 research outputs found

    Sympathetic hyperactivity syndrome following cerebral fat embolization

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    To date, there have been no reports of paroxysmal sympathetic hyperactivity syndrome (PSHS) associated with cerebral fat embolization. We describe the case of a young male who developed acute brain injury and acute hypoxemic respiratory failure secondary to significant fat embolization following a traumatic femur injury. Our patient demonstrated episodes of significant hypertension, tachycardia, fever and extensor posturing. Extensive evaluation lead to the diagnosis and appropriate treatment for PSHS. Ultimately, the patient went on to have a good neurologic recovery after a prolonged hospitalization. We will discuss PSHS diagnostic criteria, pathophysiology and treatment options. This diagnosis should be considered in all brain-injured patients with paroxysms of autonomic instability and abnormal movements

    Sympathetic hyperactivity syndrome following cerebral fat embolization

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    To date, there have been no reports of paroxysmal sympathetic hyperactivity syndrome (PSHS) associated with cerebral fat embolization. We describe the case of a young male who developed acute brain injury and acute hypoxemic respiratory failure secondary to significant fat embolization following a traumatic femur injury. Our patient demonstrated episodes of significant hypertension, tachycardia, fever and extensor posturing. Extensive evaluation lead to the diagnosis and appropriate treatment for PSHS. Ultimately, the patient went on to have a good neurologic recovery after a prolonged hospitalization. We will discuss PSHS diagnostic criteria, pathophysiology and treatment options. This diagnosis should be considered in all brain-injured patients with paroxysms of autonomic instability and abnormal movements

    CryoEM structure of the Vibrio cholerae Type IV competence pilus secretin PilQ

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    Natural transformation is the process by which bacteria take up genetic material from their environment and integrate it into their genome by homologous recombination. It represents one mode of horizontal gene transfer and contributes to the spread of traits like antibiotic resistance. In Vibrio cholerae, the Type IV competence pilus is thought to facilitate natural transformation by extending from the cell surface, binding to exogenous DNA, and retracting to thread this DNA through the outer membrane secretin, PilQ. A lack of structural information has hindered our understanding of this process, however. Here, we solved the first ever high-resolution structure of a Type IV competence pilus secretin. A functional tagged allele of VcPilQ purified from native V. cholerae cells was used to determine the cryoEM structure of the PilQ secretin in amphipol to ~2.7 Å. This structure highlights for the first time key differences in the architecture of the Type IV competence pilus secretin from the Type II and Type III Secretin System secretins. Based on our cryoEM structure, we designed a series of mutants to interrogate the mechanism of PilQ. These experiments provide insight into the channel that DNA likely traverses to promote the spread of antibiotic resistance via horizontal gene transfer by natural transformation. We prove that it is possible to reduce pilus biogenesis and natural transformation by sealing the gate, suggesting VcPilQ as a new drug target

    CryoEM structure of the Vibrio cholerae Type IV competence pilus secretin PilQ

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    Natural transformation is the process by which bacteria take up genetic material from their environment and integrate it into their genome by homologous recombination. It represents one mode of horizontal gene transfer and contributes to the spread of traits like antibiotic resistance. In Vibrio cholerae, the Type IV competence pilus is thought to facilitate natural transformation by extending from the cell surface, binding to exogenous DNA, and retracting to thread this DNA through the outer membrane secretin, PilQ. A lack of structural information has hindered our understanding of this process, however. Here, we solved the first ever high-resolution structure of a Type IV competence pilus secretin. A functional tagged allele of VcPilQ purified from native V. cholerae cells was used to determine the cryoEM structure of the PilQ secretin in amphipol to ~2.7 Å. This structure highlights for the first time key differences in the architecture of the Type IV competence pilus secretin from the Type II and Type III Secretin System secretins. Based on our cryoEM structure, we designed a series of mutants to interrogate the mechanism of PilQ. These experiments provide insight into the channel that DNA likely traverses to promote the spread of antibiotic resistance via horizontal gene transfer by natural transformation. We prove that it is possible to reduce pilus biogenesis and natural transformation by sealing the gate, suggesting VcPilQ as a new drug target

    Changes in EMG and Finger Force with Repeated Hangs from the Hands in Rock Climbers

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    The nature and degree of fatigue in muscles that control finger position during repeated sustained efforts in rock climbing have not been described. The purpose of this study was to identify changes in maximum hang time and forearm electromyogram (EMG) during repeated maximum duration hangs from a simulated rock feature. A second objective was to determine the effect of different recovery times between hangs upon changes in finger force. Five experienced rock climbers performed 2 test sessions on different days in a randomized order. Each session involved 8 repetitions of a maximum duration hang with either 1 min (R1) or 3 min (R3) resting recovery between hangs. Finger force (FF) was measured for the right hand via a piezoelectric force sensor fitted with a plate to accept the distal digits of four fingers. Peak EMG (EMGPK) and EMG Area (EMGAREA) were recorded from the anterior forearm for each hang and standardized as percent of maximum FF EMG prior to statistical analysis. Hang duration progressively decreased over repetitions but tended to plateau around repetition 5 for both R1 and R3 conditions. A significant difference was found for both recovery conditions and repetitions (p\u3c.05) as well as a significant interaction of the two factors (p\u3c.05) for hang duration. There were no significant differences for EMGPK among repetitions or between recovery conditions (p\u3e.05). EMGAREA decreased initially with repeated hangs during both R1 and R3 but this trend tended to plateau at repetition 3 for the R3 condition. A significant difference was found in EMGAREA for both recovery conditions and trials (p\u3c.05) as well as a significant interaction of the two factors (p\u3c.05). Mean FF decreased between pre- and post-hangs for both R1 and R3 however the difference was not significant. It was concluded that the overall decline in hang time is less with 3 min recovery vs 1 min recovery between hangs. Peak EMG does not appear to change despite this evidence of fatigue. A 3 min recovery interval between hang repetitions decreases the magnitude of fatigue experienced and enables a greater EMGAREA per hang

    CryoEM structure of the type IVa pilus secretin required for natural competence in Vibrio cholerae

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    Natural transformation is the process by which bacteria take up genetic material from their environment and integrate it into their genome by homologous recombination. It represents one mode of horizontal gene transfer and contributes to the spread of traits like antibiotic resistance. In Vibrio cholerae, a type IVa pilus (T4aP) is thought to facilitate natural transformation by extending from the cell surface, binding to exogenous DNA, and retracting to thread this DNA through the outer membrane secretin, PilQ. Here, we use a functional tagged allele of VcPilQ purified from native V. cholerae cells to determine the cryoEM structure of the VcPilQ secretin in amphipol to ~2.7 Å. We use bioinformatics to examine the domain architecture and gene neighborhood of T4aP secretins in Proteobacteria in comparison with VcPilQ. This structure highlights differences in the architecture of the T4aP secretin from the type II and type III secretion system secretins. Based on our cryoEM structure, we design a series of mutants to reversibly regulate VcPilQ gate dynamics. These experiments support the idea of VcPilQ as a potential druggable target and provide insight into the channel that DNA likely traverses to promote the spread of antibiotic resistance via horizontal gene transfer by natural transformation

    Age- and Sex-Associated Effects on Acute-Phase Proteins in GĂśttingen Minipigs

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    Göttingen minipigs are a useful model for diseases having an inflammatory component, and the associated use of acute-phase proteins (APP) as biomarkers of inflammation warrants establishment of their reference ranges. The objective of this study was to establish reference values for selected APP in Göttingen minipigs and to investigate the effects of age, sex, and various stimuli on these ranges. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, pig major acute-phase protein (PMAP), albumin, and porcine α-1 acid glycoprotein (PAGP) were evaluated in 4 age groups (6, 16, 24 and 40–48 wk) of male and female Göttingen minipigs. In addition, minipigs were tested under 2 housing conditions, after acute LPS challenge, and after diet-induced obesity with and without mild diabetes. Changing the pigs to a new environment induced significant increases in CRP, PMAP, haptoglobin and PAGP and a decrease in albumin. An acute LPS stimulus increased CRP, PMAP, haptoglobin, and SAA; PAGP was unchanged and albumin decreased. Obese pigs with and without diabetes showed increases in CRP and PAGP, albumin decreased, and haptoglobin and SAA were unchanged. PMAP was increased only in obese pigs without diabetes. In conclusion, reference values for CRP, PMAP, haptoglobin, SAA, PAGP and albumin were established for male and female Göttingen minipigs of different ages. These APP were influenced by age and sex, underlining the importance of considering these factors when designing and interpreting studies including aspects of inflammation. In addition, an APP response was verified after both acute and chronic stimuli

    Effects of Transdermal Fentanyl Treatment on Acute Pain and Inflammation in Rats with Adjuvant-induced Monoarthritis

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    Eliminating unnecessary pain is an important requirement of performing animal experimentation, including reducing and controlling pain of animals used in pain research. The goal of this study was to refine an adjuvant-induced monoarthritis model in rats by providing analgesia with a transdermal fentanyl solution (TFS). Male and female Sprague-Dawley rats, single- or pair-housed, were injected with 20 ÎźL of complete Freund adjuvant (CFA) into the left ankle joint. CFA-injected rats treated with a single dose of transdermal fentanyl solution (0.33 or 1 mg/kg) were compared with an untreated CFA-injected group and sham groups that received either no treatment or TFS treatment (1 mg/kg) during 72 h. At the tested doses, TFS reduced mechanical hyperalgesia and improved the mobility, stance, rearing, and lameness scores at 6 h after CFA injection. Joint circumferences were not reduced by TFS treatment, and no significant differences were detected between the 2 doses of TFS, or between single- and pair-housed rats. Treatment with TFS did not appear to interfere with model development and characteristics. However, overall, the analgesic effect was transient, and several opioid-related side effects were observed
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