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Spatiotemporal regulation of intracellular signaling molecules, such as the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), ensures proper cellular function. Liquid-liquid phase separation (LLPS) of the ubiquitous PKA regulatory subunit RIα promotes cAMP compartmentation and signaling specificity. However, the molecular determinants of RIα LLPS remain unclear. Here, we reveal that two separate dimerization interfaces, combined with the cAMP-induced unleashing of the PKA catalytic subunit (PKA-C) from the pseudosubstrate inhibitory sequence, drive RIα condensate formation in the cytosol of mammalian cells, which is antagonized by docking to A-kinase anchoring proteins. Strikingly, we find that the RIα pseudosubstrate region is critically involved in forming a non-canonical R:C complex, which recruits active PKA-C to RIα condensates to maintain low basal PKA activity in the cytosol. Our results suggest that RIα LLPS not only facilitates cAMP compartmentation but also spatially restrains active PKA-C, thus highlighting the functional versatility of biomolecular condensates in driving signaling specificity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

cAMP is a ubiquitous second messenger involved in the regulation of diverse cellular processes. Spatiotemporal regulation of cAMP through compartmentalization within various subcellular microdomains is essential to ensure specific signaling. In the following protocol, we describe a method for directly visualizing signaling dynamics within cAMP microdomains using fluorescent sensors targeted to endogenous proteins (FluoSTEPs). Instead of overexpressing a biosensor-tagged protein of interest to target a microdomain, FluoSTEP Indicator of cAMP using Epac (FluoSTEP-ICUE) utilizes spontaneously complementing split GFP and CRISPR-Cas9 genome editing to localize a FRET-based cAMP biosensor to an endogenously expressed protein of interest. Utilizing this approach, FluoSTEP-ICUE can be used to measure cAMP levels within endogenous signaling compartments, thus providing a powerful tool for studying the spatiotemporal regulation of cAMP signaling., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

We have been testing the theory used to calculate internal-conversion coefficients (ICCs) by making a series of measurements of α K values with precision better than ±2%. So far we have measured E3 transitions in three nuclei, 103 Rh, 111 Cd and 134 Cs; and M4 transitions in six nuclei, 119 Sn, 125 Te, 127 Te, 137 Ba, 193 Ir and 197 Pt. Together, these span a wide range of A and Z values. In all cases, the results strongly favor Dirac-Fock calculations in which the final-state electron wave function has been computed in an atomic field that includes the vacancy created by the internal-conversion process., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The goal of this study was to validate the cigar box arthroscopy trainer (CBAT) as a training tool and then compare its effectiveness to didactic training and to another previously validated low-fidelity but anatomic model, the anatomic knee arthroscopy trainer (AKAT)., Methods: A nonanatomic knee arthroscopy training module was developed at our institution. Twenty-four medical students with no prior arthroscopic or laparoscopic experience were enrolled as subjects. Eight subjects served as controls. The remaining 16 subjects were randomized to participate in 4 hours of either the CBAT or a previously validated AKAT. Subjects' skills were assessed by 1 of 2 faculty members through repeated attempts at performing a diagnostic knee arthroscopy on a cadaveric specimen. Objective scores were given using a minimally adapted version of the Basic Arthroscopic Knee Skill Scoring System. Total cost differences were calculated., Results: Seventy-five percent of subjects in the CBAT and AKAT groups succeeded in reaching minimum proficiency in the allotted time compared with 25% in the control group (P < .05). There was no significant difference in the number of attempts to reach proficiency between the CBAT and AKAT groups. The cost to build the CBAT was $44.12, whereas the cost was $324.33 for the AKAT., Conclusions: This pilot study suggests the CBAT is an effective knee arthroscopy trainer that may decrease the learning curve of residents without significant cost to a residency program. This study demonstrates the need for an agreed-upon objective scoring system to properly evaluate residents and compare the effectiveness of different training tools., (Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: Dementia is a debilitating illness with a disproportionate burden in patients with type 2 diabetes (T2D). Among the contributors, genetic variation at the apolipoprotein E locus (APOE) is posited to convey a strong effect. This study compared and contrasted the association of APOE with cognitive performance and cerebral structure in the setting of T2D., Research Design and Methods: European Americans from the Diabetes Heart Study (DHS) MIND (n = 754) and African Americans from the African American (AA)-DHS MIND (n = 517) were examined. The cognitive battery assessed executive function, memory, and global cognition, and brain MRI was performed., Results: In European Americans and African Americans, the APOE E4 risk haplotype group was associated with poorer performance on the modified Mini-Mental Status Examination (P < 0.017), a measure of global cognition. In contrast to the literature, the APOE E2 haplotype group, which was overrepresented in these participants with T2D, was associated with poorer Rey Auditory Verbal Learning Test performance (P < 0.032). Nominal associations between APOE haplotype groups and MRI-determined cerebral structure were observed., Conclusions: Compared with APOE E3 carriers, E2 and E4 carriers performed worse in the cognitive domains of memory and global cognition. Identification of genetic contributors remains critical to understanding new pathways to prevent and treat dementia in the setting of T2D., (© 2016 by the American Diabetes Association.)

Recognition of the normal magnetic resonance (MR) imaging appearances of the capsular ligaments of the knee is of great importance. These ligaments contribute to stability of the knee joint and are frequently injured. In this article, we describe the normal MR imaging anatomy of the capsular ligaments of the knee including the lateral and medial collateral ligamentous complexes, the extensor mechanism, and the supporting ligamentous structures of the proximal tibiofibular joint. Normal MR imaging findings and important anatomic variants of the neurovascular structures of the knee are also described., (Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.)

Ligamentous and tendinous structures of the posterolateral corner of the knee provide important static and dynamic stability to the knee joint and act in conjunction with anterior and posterior cruciate ligaments. Injuries of these structures are not uncommon. Failure to treat posterolateral corner injuries leads to posterolateral instability of the knee and subsequently poor outcome of cruciate ligament reconstructions. Currently, MRI is the diagnostic modality of choice in the evaluation of posterolateral corner injuries of the knee. We review normal MR imaging anatomy of the complex anatomical structures of the posterolateral corner of the knee, their biomechanical function, injuries, and current treatment options., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Complex capsular ligamentous structures contribute to stability of the knee joint. Simultaneous injury of two or more knee ligaments, aside from concurrent tears involving the anterior cruciate and medial collateral ligaments, is considered to be associated with femorotibial knee dislocations. Proximal tibiofibular joint dislocations are not always easily recognized and may be overlooked or missed. Patellofemoral dislocations can be transient with MR imaging sometimes required to reach the diagnosis. In this article, the authors describe the mechanism of injury, ligamentous disruptions, imaging, and treatment options of various types of knee dislocations including injuries of the femorotibial, proximal tibiofibular, and patellofemoral joints.

Because of angular-momentum conservation, superallowed β decay between 0(+) analog states involves only the vector part of the weak interaction, so its measured ft value can be used to determine the vector coupling constant, G(V). If many such transitions are measured, then the constancy of G(V) can be established and several important tests made on fundamentals of the electroweak Standard Model. We have developed apparatus that allows us to measure half-lives to ±0.03% and branching ratios to ±0.1% or better, for cyclotron-produced activities with half-lives as short as 100 ms. We present an overview of the equipment and a summary of more than 10 years of results., (© 2013 Published by Elsevier Ltd.)

In a research program aimed at testing calculated internal-conversion coefficients (ICCs), we have made precise measurements of αK values for transitions in five nuclei, (197)Pt, (193)Ir, (137)Ba, (134)Cs and (119)Sn, which span a wide range of A and Z values. In all cases, the results strongly favor calculations in which the final-state electron wave function has been computed using a potential that includes the atomic vacancy created by the internal-conversion process., (© 2013 Published by Elsevier Ltd.)

We report the first branching-ratio measurement of the superallowed 0+→0+β transition from Ca38. The result, 0.7728(16), leads to an ft value of 3062.3(68) s with a relative precision of ±0.2%. This makes possible a high-precision comparison of the ft values for the mirror superallowed transitions, Ca38→38mK and K38m→Ar38, which sensitively tests the isospin symmetry-breaking corrections required to extract Vud, the up-down quark-mixing element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix, from superallowed β decay. The result supports the corrections currently used and points the way to even tighter constraints on CKM unitarity.

Background: Studies have reported high rates of transfusion in shoulder arthroplasty. This study was conducted to evaluate the rate of transfusion at our institution, to confirm reported risk factors for transfusion, and to look for changes over time.We hypothesized that transfusion rates associated with shoulder arthroplasty at our institution are lower than those recently reported and that the incidence of transfusion is higher in individuals with low preoperative hemoglobin, with revision arthroplasty, and in older individuals., Materials and Methods: A retrospective review of 366 shoulder arthroplasties (323 patients) was performed. This included total shoulder arthroplasties, hemiarthroplasties, revision arthroplasties, and reverse total shoulder arthroplasties. Logistic regression analysis evaluated the association of clinical variables with transfusion. Early (1996-2005) and late (2006-2009) groups were compared to evaluate changes in demographics and transfusion rates over time., Results: The overall transfusion rate was 7.4% (27 of 339). Predictors of transfusion were higher intraoperative blood loss, low preoperative hemoglobin level, and humeral cement fixation. Procedure type was not predictive of transfusion. There was no difference in transfusion rates between the early and late groups, but the late group had an increased use of general anesthesia combined with a regional block, increased intraoperative blood loss, and increased use of sequential compression devices for venous thromboembolism prophylaxis., Conclusions: Lower preoperative hemoglobin, higher intraoperative blood loss, and humeral cement fixation were predictors of transfusion, but not female sex, increasing age, type of procedure, or comorbidities., (Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Recently, Jenkins, Fischbach and collaborators have claimed evidence that radionuclide half-lives vary systematically over a ±0.1% range as a function of the oscillating distance between the Earth and the Sun, based on multi-year activity measurements. We have avoided the time-dependent instabilities to which such measurements are susceptible by directly measuring the half-life of (198)Au (t(1/2)=2.695 d) on seven occasions spread out in time to cover the complete range of Earth-Sun distances. We observe no systematic oscillations in half-life and can set an upper limit on their amplitude of ±0.02%., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Magnetic resonance imaging (MRI) is routinely used in the diagnosis of sports-related knee injuries., Purpose: To determine the accuracy, sensitivity, and specificity of MRI compared with clinical evaluation in the diagnosis of meniscal pathology when the MRI facility and the radiologist are not preselected., Methods: A total of 288 knee arthroscopies were retrospectively compared. Patients were divided into 3 groups: those who had MRI performed and interpreted at a single institution, MRI performed and interpreted at community facilities, or a clinical evaluation by a senior orthopaedic surgeon., Results: The sensitivity, specificity, and accuracy of the diagnosis of medial meniscal pathology at a single institution were 90%, 59%, 76%; in community facilities, 73%, 68%, 70%; and by a clinical evaluation, 93%, 55%, 73%, respectively. For lateral meniscal pathology, the results were as follows: single institution, 75%, 76%, 81%; community facilities, 60%, 88%, 79%; and clinical evaluation, 45%, 90%, 79%, respectively. Sensitivity for medial meniscus was greater than for lateral meniscus, but specificity of diagnosis was better for lateral meniscus by MRI and clinical evaluation. While not statistically significant, there was increased sensitivity in the diagnosis of medial meniscus and lateral meniscus at SIs, but they have less specificity than at community facilities. The number of false-positive diagnoses (ie, no intra-articular pathology) that resulted in surgery was 4 of 288 (1.39%). The overall accuracy for medial meniscus by MRI was 73% vs 73% for clinical evaluation. The overall accuracy for MRI for lateral meniscus was 78% vs 79% for clinical evaluation., Conclusion: Routine MRI may not be more beneficial than clinical evaluation when there is no preselection of MRI facility and interpreting radiologist., Clinical Relevance: The use of MRI for diagnosing meniscal pathology should be reserved for those cases where the orthopaedic clinical examination is ambiguous.

A precision measurement of the γ yields following the β decay of (32)Cl has determined its isobaric-analogue branch to be (22.47(-0.18)(+0.21))%. Since it is an almost pure-Fermi decay, we can also determine the amount of isospin-symmetry breaking in this superallowed transition. We find a very large value, δ(C) = 5.3(9)%, in agreement with a shell-model calculation. This result sets a benchmark for isospin-symmetry-breaking calculations and lends support for similarly calculated, yet smaller, corrections that are currently applied to 0+ → 0 + transitions for tests of the standard model.

When radioactive isotopes that decay by alpha, beta(-), beta(+) and electron-capture transitions are placed in a conducting host material, it has recently been claimed that their half-lives show a significant dependence on temperature-up to a 6% difference between room temperature and 12K. We have refuted two of these claims by measuring: (1) the beta(-) decay of (198)Au in gold, for which we find the half life to be the same within 0.04% between room temperature and 19K; and (2) the electron-capture decay of (97)Ru in ruthenium, for which we find any half-life difference to be <0.1%., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The superallowed beta-decay Q(EC) values of (34)Cl and (38)K(m) have been measured with an online Penning trap to be 5491.662(47) keV and 6044.223(41) keV, respectively. The new values are more precise than the previous high-precision reaction-based values but are consistent with them and establish that there are no significant systematic differences between the two types of measurements.

Using the 165.9-keV M1 transition in (139)La as a calibrant, we have determined the K-shell internal conversion coefficients (ICCs) for the 127.5-keV E3 transition in (134)Cs and the 661.7-keV M4 transition in (137)Ba to 0.6% precision. Unlike previous less-precise measurements of these ICCs, which differed significantly from calculated values, our results agree well with calculations that include the atomic K-shell vacancy and disagree with those that exclude it. These results, which are consistent with what we also found for (193)Ir, confirm our earlier conclusions but for different energies, multipolarities and atomic numbers.

Using a new fast cleaning procedure to prepare isomerically pure ion samples, we have measured the beta-decay Q(EC) values of the superallowed beta emitters 5(0)Mn and (54)Co to be 7634.48(7) and 8244.54(10) keV, respectively, results which differ significantly from the previously accepted values. The corrected Ft values derived from our results strongly support new isospin-symmetry-breaking corrections that lead to a higher value of the up-down quark mixing element V(ud) and improved confirmation of the unitarity of the Cabibbo-Kobayashi-Maskawa matrix.

The beta-decay Q(EC) values of the superallowed beta emitters 26Alm, 42Sc, and 46V have been measured with a Penning trap to a relative precision of better than 8 x 10(-9). Our result for 46V, 7052.72(31) keV, confirms a recent measurement that differed from the previously accepted reaction-based Q(EC) value. However, our results for 26Alm and 42Sc, 4232.83(13) keV and 6426.13(21) keV, are consistent with previous reaction-based values. By eliminating the possibility of a systematic difference between the two techniques, this result demonstrates that no significant shift in the deduced value of Vud should be anticipated.

Precise measurements of K-shell internal conversion coefficients (ICCs) are being used to determine the best method for calculating these coefficients. A recent result for the M4 transition from 193Irm has been refined, demonstrating conclusively that the atomic vacancy created by the ejected electron must be properly accounted for in the calculation of ICCs. Measurements of additional cases are discussed.

The masses of the radioactive nuclei (46)V and its decay daughter (46)Ti have been measured with the Canadian Penning Trap on-line Penning trap mass spectrometer to a precision of 1 x 10(-8). A Q(EC) value of 7052.90(40) keV for the superallowed beta decay of (46)V is obtained from the difference of these two masses. With this precise Q value, the Ft value for this decay is determined with improved precision. An investigation of an earlier Q-value measurement for (46)V uncovers a set of 7 measurements that cannot be reconciled with modern data and affects previous evaluations of V(ud) from superallowed Fermi decays. A new evaluation, adding our new data and removing the discredited subset, yields new values for G(V) and V(ud). When combined with recent results for V(us), this yields modified constraints for the unitarity of the Cabibbo-Kobayashi-Maskawa matrix and other extensions of the standard model.

A new survey of all world data on superallowed beta decays provides demanding tests of, and tight constraints on, the weak interaction. In confirmation of the conserved vector current hypothesis, the vector coupling constant G(V) is demonstrated to be constant to better than three parts in 10(4), and any induced scalar current is limited to f(S)

Previously we used relative and absolute efficiency measurements combined with Monte Carlo calculations to define the efficiency of an HPGe gamma-ray detector with 0.2% accuracy from 50 to 1400 keV. This work has been extended to 4.8 MeV with measurements of relative efficiencies from 24Na, 56Co, and 66Ga sources. The combined results of experiment and calculation yield an efficiency curve up to 3.5 MeV with 0.4% accuracy. Single- and double-escape peak contributions also agree with calculation if positron annihilation-in-flight is incorporated.

The half-life, 3.8755(12) s, and superallowed branching ratio, 0.5315(12), for 22Mg beta decay have been measured with high precision. The latter depended on gamma-ray intensities being measured with an HPGe detector calibrated for relative efficiencies to an unprecedented 0.15%. Previous precise measurements of 0+ --> 0+ transitions have been restricted to the nine that populate stable daughter nuclei. No more such cases exist, and any improvement in a critical Cabibbo-Kobayashi-Maskawa unitarity test must depend on precise measurements of more exotic nuclei. With this branching-ratio measurement, we show those to be possible for T(z)=-1 parents. We obtain a corrected Ft value of 3071(9) s, in good agreement with expectations.

The most precise value of V(ud), which is obtained from superallowed nuclear beta decay, leads to a violation of Cabibbo-Kobayashi-Maskawa unitarity by 2.2sigma. Experiments are underway on two continents to test and improve this result through decay studies of odd-odd N = Z nuclei with A>or=62. We show, in a series of illustrative shell-model calculations, that numerous weak Gamow-Teller branches are expected to compete with the superallowed branch in each of these nuclei. Though the total Gamow-Teller strength is significant, many of the individual branches will be unobservably weak. Thus, new techniques must be developed if reliable ft values are to be obtained with 0.1% precision for the superallowed branches.

Activity determination by gamma-ray spectrometry is a valuable aid which is widely used where radioactive sources are applied. For the construction of an efficiency curve vs. energy in a standard geometry, the accuracy is limited not only by the uncertainty of peak area determination and the knowledge of the relevant emission probabilities but also by the uncertainties of the activity values applied to efficiency calibration with standard sources. Recently, a method to determine a relative efficiency function using selected radionuclides with gamma cascades of well known emission probabilities has been developed which yields very accurate efficiency values. Such a curve has to be converted into an absolute efficiency curve by calibration of the detector system with at least one source of very well known activity. Especially for this purpose, a set of Co-60 gamma-ray spectrometer sources was produced at the PTB. The activity values (10-45 kBq) were measured by the 4pi beta-gamma coincidence technique with a standard uncertainty of less than 0.1%. Production and measurement of these sources are described in the present paper. Special care was taken to include all contributions to the standard uncertainty of the activity value when establishing the uncertainty budget for the activity of each of these sources. The activity ratio of two of these sources, as obtained by the absolute measurements, was checked by independent gamma-ray counting at two other laboratories, where the precision achieved was less than 0.2%. The procedure described is considered to be a step towards more accurately determined efficiency functions in gamma-ray spectrometry.

With the goal of measuring precise gamma-ray intensities for short-lived (< 5 s) accelerator-produced activities, we have calibrated the efficiency of an HPGe detector between 53 and 1836keV to sub-percent precision with a combination of source measurements and Monte Carlo calculations. Using known or independently measured detector dimensions, we have achieved both relative and absolute agreement (the latter, to 0.1%) between the calculated and measured efficiencies with only two adjustable detector parameters, the thicknesses of the contact dead layers.

Obstructive apnea and voluntary breath holding are associated with transient increases in muscle sympathetic nerve activity (MSNA) and arterial pressure. The contribution of changes in blood flow relative to the contribution of changes in vascular resistance to the apnea-induced transient rise in arterial pressure is unclear. We measured heart rate, mean arterial blood pressure (MAP), MSNA (peroneal microneurography), and femoral artery blood velocity (V(FA), Doppler) in humans during voluntary end-expiratory apnea while they were exposed to room air, hypoxia (10.5% inspiratory fraction of O2), and hyperoxia (100% inspiratory fraction of O2). Changes from baseline of leg blood flow (Q) and vascular resistance (R) were estimated from the following relationships: Q proportional to V(FA), corrected for the heart rate, and R proportional to MAP/Q. During apnea, MSNA rose; this rise in MSNA was followed by a rise in MAP, which peaked a few seconds after resumption of breathing. Responses of MSNA and MAP to apnea were greatest during hypoxia and smallest during hyperoxia (P < 0.05 for both compared with room air breathing). Similarly, apnea was associated with a decrease in Q and an increase in R. The decrease in Q was greatest during hypoxia and smallest during hyperoxia (-25 +/- 3 vs. -6 +/- 4%, P < 0.05), and the increase in R was the greatest during hypoxia and the least during hyperoxia (60 +/- 8 vs. 21 +/- 6%, P < 0.05). Thus voluntary apnea is associated with vasoconstriction, which is in part mediated by the sympathetic nervous system. Because apnea-induced vasoconstriction is most intense during hypoxia and attenuated during hyperoxia, it appears to depend at least in part on stimulation of arterial chemoreceptors.

Presently, the world data for superallowed beta decay leads to a result in disagreement (at the 98% confidence level) with the predictions of the minimal standard model for the unitarity of the Cabibbo-Kobayashi-Maskawa matrix. Precise data for the superallowed 0(+)-->0(+) beta decay of (74)Rb would provide a critical test of the nucleus-dependent isospin symmetry-breaking corrections that must be calculated for these superallowed Fermi beta decays. The present work reports the first precise measurement of the half-life for (74)Rb ( t(1/2) = 64.761+/-0.031 ms). The data were obtained at the radioactive beam facility (ISAC) at TRIUMF using a beam of approximately 4000 (74)Rb ions s(-1).

A novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno[1,2-e]pyrazin derivatives was synthesized. One of them, the 9-(1H-tetrazol-5-ylmethyl)-4-oxo-5,10-dihydroimidazo[1,2-a]indeno[1,2-e]pyrazin-2-yl phosphonic acid 4i exhibited a strong and a selective binding affinity for the AMPA receptor (IC50 = 13 nM) and demonstrated potent antagonist activity (IC50 = 6nM) at the ionotropic AMPA receptor. This compound also displayed good anticonvulsant properties against electrically-induced convulsions after ip and iv administration with ED50 values between 0.8 and 1 mg/kg. Furthermore, a strong increase in potency was observed when given iv 3 h before test (ED50 = 3.5 instead of 25.6 mg/kg for the corresponding 9-carboxymethyl-2-carboxylic acid analogue). These data confirmed that there is an advantage in replacing the classical carboxy substituents by their bioisosteres such as tetrazole or phosphonic acid groups.

Background and Objectives: To identify if any process steps used in plasma fractionation may have a capability of removing agents of human transmissible spongiform encephalopathy (TSE)., Materials and Methods: Sixteen fractionation steps were investigated separately by adding a preparation of hamster adapted scrapie 263K to the starting material at each process step and determining the distribution into resultant fractions of protease-K-resistant (abnormal) prion protein by Western blot analysis., Results: A number of process operations were found to remove abnormal prion protein to the limit of detection of the assay. These were cold ethanol precipitation of fraction IV (log reduction, LR, >/=3.0) and a depth filtration (LR >/=4.9) in the albumin process; cold ethanol fraction I+III precipitation (LR >/=3.7) and a depth filtration (LR >/=2.8) in the immunoglobulin processes and adsorption with DEAE-Toyopearl 650M ion exchanger (LR >/=3.5) in the fibrinogen process. In addition, a substantial degree of removal of abnormal prion protein was observed across DEAE-Toyopearl 650M ion exchange (LR = 3.1) used in the preparation of factor-VIII concentrate; DEAE-cellulose ion exchange (LR = 3.0) and DEAE-sepharose ion exchange (LR = 3.0) used in the preparation of factor-IX concentrates and S-sepharose ion exchange (LR = 2.9) used in the preparation of thrombin., Conclusions: Plasma fractionation processes used in the manufacture of albumin, immunoglobulins, factor-VIII concentrate, factor-IX concentrates, fibrinogen and thrombin all contain steps which may be capable of removing causative agents of human TSEs.

We report the first case of a United States Air Force pilot returned to flying status after cardiac valve replacement. A 34-yr-old C-130 pilot underwent placement of an aortic valve homograft as a result of an episode of acute bacterial endocarditis on a bicuspid aortic valve. After a period of observation and a careful evaluation, he was returned to flying status in low-G aircraft. While cardiac valve replacement has traditionally been considered disqualifying for military aviation duties, aortic valve homografts have been associated with a lower morbidity and a significantly improved prognosis when compared to the other types of prosthetic heart valves. With careful evaluation and close follow-up, military aviators with aortic valve homografts can be considered for return to flying duties in low-G aircraft.

Previously, we showed that forearm venous congestion augmented muscle sympathetic nerve activity (MSNA) during static exercise. We postulated that venous congestion increased interstitial pressure, sensitizing mechanoreceptor afferents that led to a greater sympathoexcitation during exercise. In this study, we tested the hypothesis that forearm compression (FC) would increase interstitial pressure and selectively stimulate mechanically sensitive afferents. We measured MSNA during 2 min of ischemic static exercise (40% maximal voluntary contraction) and 2 min of posthandgrip circulatory arrest. Exercise was performed again after 5 min of FC induced by inflation of a forearm cuff to 90 mmHg (n = 6) and 110 mmHg (n = 7). FC without exercise had no effect on any of the hemodynamic variables. MSNA and mean arterial blood pressure responses were not augmented when exercise was performed with FC at 90 mmHg. However, static exercise coupled with FC at 110 mmHg did augment the reflex responses to static exercise (changes in MSNA before and after FC were 277 +/- 58 and 503 +/- 82 arbitrary units, respectively, P < 0.02; changes in mean arterial pressure before and after FC were 35 +/- 4 and 41 +/- 5 mmHg, respectively, P < 0.003). These responses were probably not due to greater metaboreceptor stimulation, since posthandgrip circulatory arrest responses were unaffected by FC. We postulate that FC sensitizes mechanoreceptors, leading to greater sympathoexcitation during exercise.

Oscillations of arterial pressure during sleep are the hemodynamic hallmark of the sleep apnea syndrome. The mechanism of these transient pressure elevations is incompletely understood. To investigate the role of the arterial chemoreflex in the neurocirculatory responses to apnea, we measured mean arterial pressure (MAP; Finapres) and muscle sympathetic nerve activity (MSNA; peroneal microneurography) during voluntary end-expiratory apnea during exposure to room air, 10.5% O2 in N2 (hypoxemia), and 100% O2 (hyperoxia) in 11 healthy men. While the men breathed spontaneously, MSNA (in bursts/min) rose during hypoxemia and decreased during hyperoxia and MAP remained unchanged. During room air exposure, apnea led to a rise of 94 +/- 54% in MSNA total amplitude and a rise of 6.5 +/- 2.1 mmHg in MAP. MSNA and MAP increased by 616 +/- 158% and 10.8 +/- 2.4 mmHg, respectively, during hypoxemic apnea of equal duration (time-matched responses) and by 98 +/- 41% and 4.9 +/- 2.0 mmHg, respectively, during hyperoxic apnea (P < 0.05 for hypoxemic vs. hyperoxic apnea for both). Thus, in awake healthy humans, activation of the arterial chemoreflex by hypoxemia appears to contribute importantly to the sympathetic and blood pressure responses to apnea.

Exercise is a potent stimulus to activate the sympathetic nervous system. Previous work suggests that metabolite-sensitive muscle afferents are activated near the point of fatigue, and, when activated, they determine the muscle sympathetic nerve activity (MSNA) response to isometric forearm exercise. Yet, studies using a more prolonged rhythmic exercise paradigm suggest that the sympathetic nervous system can be activated in a more graded fashion. The purpose of this study was to determine whether metaboreceptor stimulation would also be responsible for MSNA responses to prolonged rhythmic isotonic forearm exercise. Subjects (n = 16) performed rhythmic isotonic forearm exercise at 25% maximal voluntary contraction for 30 min as we measured MSNA (microneurography). We observed progressive increases in MSNA with a peak increase of 161 units from a baseline value of 180 units. We also performed posthandgrip circulatory arrest (PHG-CA) in nine of these subjects. This maneuver isolates the metaboreceptor contribution to MSNA. During PHG-CA, delta MSNA values were not different from those observed during a freely perfused recovery period (n = 7). We also compared MSNA responses during the rhythmic paradigm with those seen during a static protocol at 40% of maximal voluntary contraction in five subjects. The two types of exercise caused similar increases in MSNA, but only the static paradigm was associated with a sustained MSNA response during PHG-CA. Finally, 31P-nuclear magnetic resonance was used to evaluate muscle metabolic responses during rhythmic and static forearm exercise (n = 6). Static exercise caused muscle acidosis and an increase in H2PO4-, whereas rhythmic exercise had no effect on muscle metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)