Acute Alteration of Plasma Renin Activity by Large Doses of Intravenous Prednisolone

Large doses of intravenous glucocorticoids have been used in an attempt to reverse homograft rejection. The intravenous administration of 1 g prednisolone over 1 hr resulted in a significant acute reduction of plasma renin activity in 5 normal subjects tested and in 11 out of 15 patients bearing renal homografts. No definite explanation for failure to respond nor the mechanism of this prednisolone effect is readily at hand. An acute decrease in renin activity could be salutary for the chronically or acutely rejecting patient in that it could reduce vasopressor and salt-retaining effects. However, several of the non-responders had an increase in renin activity which could have been detrimental. © 1972, SAGE Publications. All rights reserved

Coarse-grained simulations suggest potential competing roles of phosphoinositides and amphipathic helix structures in membrane curvature sensing of the AP180 N-terminal homology domain

The generation and sensing of membrane curvature by proteins has become of increasing interest to researchers with multiple mechanisms, from hydrophobic insertion to protein crowding, being identified. However, the role of charged lipids in the membrane curvature-sensing process is still far from understood. Many proteins involved in endocytosis bind phosphatidylinositol 4,5-bisphosphate (PIP2) lipids, allowing these proteins to accumulate at regions of local curvature. Here, using coarse-grained molecular dynamics simulations, we study the curvature-sensing behavior of the ANTH domain, a protein crucial for endocytosis. We selected three ANTH crystal structures containing either an intact, split, or truncated terminal amphipathic helix. On neutral membranes, the ANTH domain has innate curvature-sensing ability. In the presence of PIP2, however, only the domain with an intact helix senses curvature. Our work sheds light on the role of PIP2 and its modulation of membrane curvature sensing by proteins

Gluino Decay as a Probe of High Scale Supersymmetry Breaking

A supersymmetric standard model with heavier scalar supersymmetric particles has many attractive features. If the scalar mass scale is O(10 - 10^4) TeV, the standard model like Higgs boson with mass around 125 GeV, which is strongly favored by the LHC experiment, can be realized. However, in this scenario the scalar particles are too heavy to be produced at the LHC. In addition, if the scalar mass is much less than O(10^4) TeV, the lifetime of the gluino is too short to be measured. Therefore, it is hard to probe the scalar particles at a collider. However, a detailed study of the gluino decay reveals that two body decay of the gluino carries important information on the scalar scale. In this paper, we propose a test of this scenario by measuring the decay pattern of the gluino at the LHC.Comment: 29 pages, 9 figures; version published in JHE

Quantification of the effects of an alpha-2 adrenergic agonist on reflex properties in spinal cord injury using a system identification technique

<p>Abstract</p> <p>Background</p> <p>Despite numerous investigations, the impact of tizanidine, an anti-spastic medication, on changes in reflex and muscle mechanical properties in spasticity remains unclear. This study was designed to help us understand the mechanisms of action of tizanidine on spasticity in spinal cord injured subjects with incomplete injury, by quantifying the effects of a single dose of tizanidine on ankle muscle intrinsic and reflex components.</p> <p>Methods</p> <p>A series of perturbations was applied to the spastic ankle joint of twenty-one spinal cord injured subjects, and the resulting torques were recorded. A parallel-cascade system identification method was used to separate intrinsic and reflex torques, and to identify the contribution of these components to dynamic ankle stiffness at different ankle positions, while subjects remained relaxed.</p> <p>Results</p> <p>Following administration of a single oral dose of Tizanidine, stretch evoked joint torque at the ankle decreased significantly (p < 0.001) The peak-torque was reduced between 15% and 60% among the spinal cord injured subjects, and the average reduction was 25%. Using systems identification techniques, we found that this reduced torque could be attributed largely to a reduced reflex response, without measurable change in the muscle contribution. Reflex stiffness decreased significantly across a range of joint angles (p < 0.001) after using tizanidine. In contrast, there were no significant changes in intrinsic muscle stiffness after the administration of tizanidine.</p> <p>Conclusions</p> <p>Our findings demonstrate that tizanidine acts to reduce reflex mechanical responses substantially, without inducing comparable changes in intrinsic muscle properties in individuals with spinal cord injury. Thus, the pre-post difference in joint mechanical properties can be attributed to reflex changes alone. From a practical standpoint, use of a single "test" dose of Tizanidine may help clinicians decide whether the drug can helpful in controlling symptoms in particular subjects.</p

Associations between age and sleep apnea risk among newborn infants

ObjectiveAmong older children, sleep‐disordered breathing (SDB) is associated with measurable neurocognitive consequences. However, diagnostic SDB thresholds are lacking for infants < 12 months. We sought to evaluate the relationship between SDB indices, gestational age (GA), and postmenstrual age (PMA) for infants who underwent clinically‐indicated polysomnograms at a tertiary care center.MethodsEvery infant < 3‐months chronological age whose first clinically‐indicated polysomnogram was between 2/2012 and 2/2017 was included. Linear regression was used to evaluate associations between apnea‐hypopnea index (AHI), obstructive‐apnea index (OAI), and GA and PMA for infants with and without obvious clinical risk factors for SDB (eg, micrognathia and cleft palate).ResultsFor 53 infants without obvious SDB risk factors (GA 35.6 ± 4.5 weeks; PMA 41.2 ± 4.0 weeks), mean AHI was 27 ± 18 and OAI 2.9 ± 4.5. There was a weak inverse relationship between AHI and PMA (r2 = 0.12, P = 0.01), but AHI was not predicted by GA (r2 = 0.04, P = 0.13). Conversely, OAI was more strongly associated with GA (r2 = 0.33, P < 0.0001) than PMA (r2 = 0.08, P = 0.036). For 28 infants with congenital structural anomalies that predispose to SDB (GA 38.0 ± 3.1 weeks, PMA 43.1 ± 3.3 weeks, AHI 37.7 ± 30, OAI 8.2 ± 11.8), neither AHI nor OAI were related to PMA or GA.ConclusionsAmong infants who received clinically‐indicated polysomnograms but did not have obvious structural risk for SDB, AHI declined with advancing PMA, but obstructive‐apnea was best predicted by prematurity. In contrast, the SDB risk did not improve with increasing GA or PMA for infants with congenital structural risk factors; such infants may not outgrow their risk for SDB.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/1/ppul24354_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/2/ppul24354.pd

Evaluation of a 25-Year-Program for the Control of Schistosomiasis Mansoni in an Endemic Area in Brazil

A clinical-epidemiological reevaluation on schistosomiasis mansoni was performed in 2005, in the urban area of a little town, Comercinho, MG, specifically focusing on the inhabitants of the same area in 1981, when a first survey and treatment with oxamniquine were carried out. The surveys included: identification of the intermediary host, census, mapping of the city, socioeconomic survey, stool examination, clinical examination, research dealing with contact with natural waters, and treatment of the positive cases. From a population of 1,474 people studied in 1981, 358 were submitted to stool examination, and 231 were clinically examined. From 1981 to 1992 five specific treatments were performed with oxamniquine and the last one with praziquantel. The results obtained were compared and demonstrated that the prevalence in Comercinho decreased significantly (70.4% to 1.7%), as well as the hepatosplenic form (7% to 1.3%) in 1981 and 2005, respectively. Significant improvement in the life quality (improvement in the housing, professional qualification and basic sanitation) were observed and must be considered important for the schistosomiasis control

Improved diagnosis of virulent ovine footrot using the intA gene

Footrot is a mixed bacterial infection of the hooves of sheep. The Gram-negative anaerobic bacterium 'Dichelobacter nodosus' is the principal causative agent, with different strains causing diseases of different severity, ranging from benign to virulent. In Australia, in the state of New South Wales (NSW), only virulent footrot is subject to regulatory action, including quarantine. However, it is often difficult to distinguish benign footrot from virulent footrot in the initial stages of infection, or under adverse climatic conditions. The gelatin gel test, which measures the thermostability of secreted bacterial proteases, is the laboratory test most widely used in Australia to aid in the differential diagnosis of footrot. The proteases of virulent strains are, in general, more thermostable than the proteases of benign strains. However, there are some false positives in the gelatin gel test, which may lead to unnecessary quarantine procedures. We used Southern blot analysis on 595 isolates of 'D. nodosus' from 124 farms on which sheep had benign or virulent footrot to test for the presence of the intA gene. We found that for 'D. nodosus' strains which are stable in the gelatin gel test, there is a high correlation between the presence of the intA gene and the ability of the strain to cause virulent footrot. We also developed a PCR-based assay for the rapid detection of intA, which can be used to test DNA extracted from colonies grown on plates, or DNA extracted from cotton swabs of culture plates

Mechanisms of Esophago-Pharyngeal Acid Regurgitation in Human Subjects

Esophago-pharyngeal regurgitation is implicated in various otolaryngologic and respiratory disorders. The pathophysiological mechanisms causing regurgitation are still largely unknown