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Perioperative transesophageal echocardiography (TEE) has been part of clinical activity for more than 40 years. During this period, TEE has evolved in terms of technology and clinical applications beyond the initial fields of cardiology and cardiac surgery. The benefits of TEE in the diagnosis and management of acute hemodynamic and respiratory collapse have been recognized in noncardiac surgery and by other specialties too. This natural progress led to the development of rescue TEE, a relatively recent clinical application that extends the use of TEE and makes it accessible to a large group of clinicians and patients requiring acute care. In this review, the authors appraise the current clinical applications and evidence base around this topic. The authors provide a thorough review of the various image acquisition protocols, clinical benefits, and compare it with the more frequently used transthoracic echocardiography. Furthermore, the authors have reviewed the current training and credentialing pathways. Overall, rescue TEE is a highly attractive and useful point-of-care examination, but the current evidence base is limited and the technical protocols, training, and credentialing processes are not standardized. There is a need for adequate guidelines and high-quality research to support its application as a bedside rescue tool. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.apergo.2009.01.001 Byline: Barbara M. Haward, Christopher H. Lewis, Michael J. Griffin Abstract: The motions of vessels may interfere with crew activities and well-being, but the relationships between motion and the experiences of crew are not well-established. Crew responses to motions of a floating production and storage offshore vessel at a fixed location in the North Sea were studied over a 5-month period to identify any changes in crew difficulties and symptoms associated with changes in vessel motion. Ship motions in all six axes (fore-aft, lateral, vertical, roll, pitch, and yaw) were recorded continuously over the 5-month period while 47 crew completed a total of 1704 daily diary entries, a participation rate of 66-78% of the crew complement. The dominant oscillations had frequencies of around 0.1Hz, producing magnitudes of translational oscillation in accommodation areas of up to about 0.7ms.sup.-2 r.m.s., depending on the weather, and magnitudes up to three times greater in some other areas. The daily diaries gave ratings of difficulties with tasks, effort level, motion sickness, health symptoms, fatigue, and sleep. Problems most strongly associated with vessel motions were difficulties with physical tasks (balancing, moving and carrying), and sleep problems. Physical and mental tiredness, cognitive aspects of task performance, and stomach awareness and dizziness were also strongly associated with motion magnitude. There was a vomiting incidence of 3.1%, compared with a predicted mean vomiting incidence of 9.3% for a mixed population of unadapted adults. It is concluded that crew difficulties increase on days when vessel motions increase, with some activities and responses particularly influenced by vessel motions. Author Affiliation: Human Factors Research Unit, Institute of Sound and Vibration Research, University of Southampton, Southampton SO17 1BJ, UK Article History: Received 21 October 2007; Accepted 6 January 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.apergo.2008.06.001 Byline: Miyuki Morioka, Michael J. Griffin Abstract: Vehicle drivers receive tactile feedback from steering-wheel vibration that depends on the frequency and magnitude of the vibration. From an experiment with 12 subjects, equivalent comfort contours were determined for vertical vibration of the hands at two positions with three grip forces. The perceived intensity of the vibration was determined using the method of magnitude estimation over a range of frequencies (4-250Hz) and magnitudes (0.1-1.58ms.sup.-2 r.m.s.). Absolute thresholds for vibration perception were also determined for the two hand positions over the same frequency range. The shapes of the comfort contours were strongly dependent on vibration magnitude and also influenced by grip force, indicating that the appropriate frequency weighting depends on vibration magnitude and grip force. There was only a small effect of hand position. The findings are explained by characteristics of the Pacinian and non-Pacinian tactile channels in the glabrous skin of the hand. Author Affiliation: Human Factors Research Unit, Institute of Sound and Vibration Research, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom Article History: Received 19 September 2007; Accepted 10 June 2008

The Fontan circulation is the single-ventricle approach to surgical palliation of complex congenital heart disease wherein biventricular separation and function cannot be safely achieved. Incremental improvements in this surgical technique, along with improvements in the long-term medical management of these patients, have led to greater survival of these patients and a remarkably steady increase in the number of adults living with this unusual circulation and physiology. This has implications for healthcare providers who now have a greater chance of encountering Fontan patients during the course of their practice. This has particularly important implications for anesthesiologists because the effects of their interventions on the finely balanced Fontan circulation may be profound. The American Heart Association and American College of Cardiology recommend that, when possible, elective surgery should be performed in an adult congenital heart disease center, although this may not be feasible in the provision of true emergency care. This review article summarizes the pathophysiology pertinent to the provision of anesthesia in this complex patient group and describes important modifications to anesthetic technique and perioperative management. [ABSTRACT FROM AUTHOR]

Many children born today with congenital heart disease can expect to live long into adulthood. Improvements in surgical technique and anesthetic and perioperative care have significantly increased the number of survivors. Unfortunately, as these patients progress through life they frequently require further interventions. Although surgical intervention may be required frequently, these patients can be managed in the cardiac catheterization or electrophysiology laboratory. Surgical correction of tetralogy of Fallot can leave patients with pulmonary valve dysfunction later in life. A percutaneous approach is now available for these patients, which can obviate the need for resternotomy. During deployment of the valve, anesthesiologists should be aware that compression of coronary arteries can occur. Adult congenital heart disease (ACHD) patients often require pacemaker/implantable cardioverter- defibrillator (ICD) insertion or ablation therapy. These patients may have altered cardiac anatomy, which can make endovascular procedures extremely challenging. Recent developments have made these procedures safer and more efficient. A number of congenital cardiac conditions can also be associated with orofacial abnormalities. ACHD patients, as a result, can present with challenging airways. The catheterization laboratory may not be the optimum environment for the anesthesiologist to manage a difficult airway. The requirement of transesophageal echocardiography for some cath eterization procedures needs to be considered when deciding on an airway management plan. Knowledge of the underlying cardiac anatomy and the planned procedure is advised when providing anesthesia for this complex patient group outside the theater setting. [ABSTRACT FROM AUTHOR]

As techniques for corrective and palliative surgery in congenital heart disease improve, the number of patients surviving to become adults with congenital heart disease (ACHD) has increased. A significant proportion of these patients will progress to develop advanced heart failure, the symptoms of which vary, complicating prediction of life expectancy. Unlike acquired heart failure, there is a lack of evidence-based treatments with which to relieve symptoms and prolong survival. As a result, a number of ACHD patients will proceed to heart transplantation. Referral for transplantation should be considered early, given the difficulties with prognostication, and should take place in a center with surgical and medical expertise in the management of ACHD patients and transplantation. In addition to assessing contraindications to heart transplantation for the general population, factors specific to ACHD should be considered. These include pulmonary hypertension, cyanosis, liver disease, previous surgeries, and the degree of allosensitization. Once listed for transplantation, ACHD patients spend longer on the waitlist, and are more likely to die or be delisted than their non-ACHD counterparts. Mechanical circulatory support is used less commonly as a bridge to transplantation given the difficulties with implantation and unfamiliarity of use. Recent evidence suggests that with increased experience and early consideration, mechanical circulatory support can be used successfully as a bridging therapy. Despite a higher early mortality, long-term survival is greater for ACHD patients after transplant due to younger age and relative lack of comorbidities. With early referral, careful assessment of each individual's unique anatomy and physiology, and care in a center experienced with ACHD patients and transplantation, outcomes will continue to improve. [ABSTRACT FROM AUTHOR]

Historically, germline testing of patients with pancreatic cancer was performed selectively in patients with a strong family history of cancer. Current guidelines recommend universal testing because some patients may have actionable germline pathogenic variants without family history. We conducted a cost-effectiveness analysis using a decision-tree model to compare universal versus selective testing strategies for patients with pancreatic cancer. Costs, probabilities, and overall survival were estimated from the published literature and institutional data. One-way and probabilistic sensitivity analyses explored model uncertainty. Universal germline genetic testing had an incremental cost of $310 with an increase of 0.003 life-years. The incremental cost-effectiveness ratio was $121,924/life-years. Parameters which were most impactful (sensitivity analysis) included the median overall survival of patients with advanced disease treated with personalized therapy, cost of personalized therapy for advanced disease, and the probability of receiving personalized therapy in advanced disease. A strategy of selective testing was more cost-effective in 59% of iterations when the willingness-to-pay threshold was set to $100,000/life-years. Our model suggested that selective germline testing of patients with newly diagnosed pancreatic cancer is more cost-effective than universal testing. Additional research is needed to explore the impact of cascade testing of relatives on cost-effectiveness. [ABSTRACT FROM AUTHOR]

Abstract Background When pancreatic neoplasms occlude or encase the superior mesenteric-portal-splenic vein confluence with abutment of the posterior lateral wall of the superior mesenteric artery, a mesocaval shunt with or without a distal splenorenal shunt allows for safe dissection of the porta hepatis and separation of the pancreatic tumor from the superior mesenteric artery. Herein we report long-term results of the largest known series of portosystemic shunts performed at the time of pancreatectomy. Methods All patients who underwent pancreatic resection with a mesocaval shunt or distal splenorenal shunt were identified from our prospective database. Demographics, perioperative treatment, and outcomes were reviewed. Results A total of 34 patients underwent mesocaval shunt or distal splenorenal shunt, including 25 at the time of pancreatoduodenectomy, 6 during total pancreatectomy, and 3 after prior pancreatectomy. There were 15 mesocaval shunts, 16 distal splenorenal shunts, 2 combined mesocaval/distal splenorenal shunts, and 1 distal splenoadrenal vein shunt. The mesocaval group included 11 temporary and 6 permanent (3 delayed) shunts. Median operative time was 9 hours (range 6.5–13), median estimated blood loss was 950 mL (range 200–5,000), and median duration of hospital stay was 11 days (range 7–35). Four patients experienced complications that required intervention (Clavien-Dindo grade ≥III), but there were no 90-day mortalities. For patients with adenocarcinoma, median overall survival was 31 months at a median follow-up of 19 months. All but 1 shunt (distal splenorenal) were patent at last follow-up. Conclusion Mesenteric venous shunting facilitates a safe and complete tumor resection in patients who require a complex pancreatectomy, many of whom would otherwise be deemed inoperable. [ABSTRACT FROM AUTHOR]

Seat effective amplitude transmissibilities (SEAT values) quantify the influence of seats on discomfort caused by vibration. This study investigated SEAT values with vertical mechanical shocks at low, medium, and high magnitudes (0.5, 1.0, and 2.0 ms-1.75) at frequencies between 1.0 and 16 Hz. With 18 subjects sitting on a rigid seat and two foam cushions, SEAT values were measured objectively (from the transmitted vibration), measured subjectively (by the responses of subjects), and predicted (using a model of the seat-passenger system). Except with high magnitude low frequency shocks, predicted SEAT values were similar to measured SEAT values. With shocks causing subjects to rise off a cushion and subsequently impact the cushion (low frequencies around 1 g), subjective SEAT values were better estimated using predicted SEAT values than objectively measured SEAT values, because accelerometers on cushions exaggerated the impact of the falling subject. However, accelerometers on rigid seats will underestimate such impacts. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is an autosomal recessive disorder affecting approximately 1 in 2,500 live births worldwide, with double this estimated frequency in Ireland. CF is characterized by a genetic defect of the CF transmembrane regulator protein, causing impairment of chloride ion transportation. This has multisystem consequences, particularly in the lungs, where it results in intensely mucoid secretions, which increases susceptibility to infection. Lung transplantation is indicated in CF when there is progressive decline in a patient's functional reserve. In this report, the authors present a 6-year case review of allograft lung transplantations in 41 CF patients from the Irish National Centre for Lung Transplantation from 2010 through 2015. Preoperative risk factors for morbidity and major mortality are discussed. The authors' experience with intraoperative anesthetic challenges and management options are outlined, and postoperative complications are discussed. [ABSTRACT FROM AUTHOR]

Background Patients with locally advanced pancreatic cancer have historically been considered inoperable. The purpose of this report was to determine resectability rates for patients with locally advanced pancreatic cancer based on our recently described definitions of type A and type B locally advanced pancreatic cancer. Methods An institutional prospective pancreas cancer database was queried for consecutive patients with locally advanced pancreatic cancer treated between January 2009 and June 2017. All pretreatment imaging was re-reviewed and patients were categorized as locally advanced pancreatic cancer type A or type B. Demographics, induction therapy, resection type, and outcomes were reviewed. Results We identified 108 consecutive patients; 12 were excluded from analysis due to the absence of available pretreatment imaging or they had not yet completed all intended neoadjuvant therapy. Of the remaining 96 patients (45 type A, 51 type B), disease progression occurred in 19 (20%) during induction therapy and 30 (31%) were deemed inoperable at final preoperative restaging. Therefore, 47 (49%) of 96 patients were taken to surgery and 40 (42%) underwent successful resection (28 [62%] of 45 type A and 12 [24%] of 51 type B); an RO resection was achieved in 32 (80%). Metastatic disease was found intraoperatively (6 at laparoscopy, 1 at laparotomy) in 7 (15%) of 47 patients. There were no mortalities; 6 (15%) patients experienced major postoperative complications. Resected patients had a median overall survival of 38.9 months. Conclusion Locally advanced pancreatic cancer can be dichotomized into type A and B with distinctly different probabilities of completing all therapy to include surgery; thereby allowing goals of therapy to be established at the time of diagnosis. Multimodality therapy that includes surgery can be accomplished in selected patients with locally advanced pancreatic cancer and is associated with a median overall survival that approximates earlier stages of disease. (Surgery 2017;160:XXX-XXX.) [ABSTRACT FROM AUTHOR]

Backrests influence the comfort of seated people. With 21 subjects sitting with three backrest heights (no backrest, short backrest, high backrest) discomfort caused by lateral, roll, and fully roll-compensated lateral oscillation was investigated at frequencies between 0.25 and 1.0 Hz. With lateral oscillation, the short backrest reduced discomfort at frequencies less than 0.63 Hz and the high backrest reduced discomfort at frequencies less than 1.0 Hz. With roll oscillation, the high backrest reduced discomfort at frequencies less than 0.63 Hz, but increased discomfort at 1.0 Hz. With fully roll-compensated lateral oscillation, the short backrest reduced discomfort at 0.4 Hz and the high backrest reduced discomfort at 0.5 and 0.63 Hz. As predicted by current standards, a backrest can increase discomfort caused by high frequencies of vibration. However, a backrest can reduce discomfort caused by low frequencies, with the benefit depending on the frequency and direction of oscillation and backrest height. [ABSTRACT FROM AUTHOR]

The detection of a vibration may be reduced by the presence of another vibration: a phenomenon known as ‘masking’. This study investigated how the detection of one frequency of vibration is influenced by vibration at another frequency. With nine subjects, thresholds for detecting fore-and-aft backrest vibration were determined (for 4, 8, 16, and 31.5-Hz sinusoidal vibration) in the presence of a masker vibration (4-Hz random vibration, 1/3-octave bandwidth at six intensities). The masker vibration increased thresholds for perceiving vibration at each frequency by an amount that reduced with increasing difference between the frequency of the sinusoidal vibration and the frequency of the masker vibration. The 4-Hz random vibration almost completely masked 4-Hz sinusoidal vibration, partially masked 8- and 16-Hz vibration, and only slightly masked 31.5-Hz vibration. The findings might be explained by the involvement of different sensory systems and different body locations in the detection of different frequencies of vibration. [ABSTRACT FROM AUTHOR]

The discomfort caused by lateral oscillation, roll oscillation, and fully roll-compensated lateral oscillation has been investigated at frequencies between 0.25 and 1.0 Hz when sitting on a rigid seat and when sitting on a compliant cushion, both without a backrest. Judgements of vibration discomfort and the transmission of lateral and roll oscillation through the seat cushion were obtained with 20 subjects. Relative to the rigid seat, the cushion increased lateral acceleration and roll oscillation at the lower frequencies and also increased discomfort during lateral oscillation (at frequencies less than 0.63 Hz), roll oscillation (at frequencies less than 0.4 Hz), and fully roll-compensated lateral oscillation (at frequencies between 0.315 and 0.5 Hz). The root-sums-of-squares of the frequency-weighted lateral and roll acceleration at the seat surface predicted the greater vibration discomfort when sitting on the cushion. The frequency-dependence of the predicted discomfort may be improved by adjusting the frequency weighting for roll acceleration at frequencies between 0.25 and 1.0 Hz. [ABSTRACT FROM AUTHOR]

The extent to which a seat can provide useful attenuation of vehicle vibration depends on three factors: the characteristics of the vehicle motion, the vibration transmissibility of the seat, and the sensitivity of the body to vibration. The ‘seat effective amplitude transmissibility’ (i.e., SEAT value) reflects how these three factors vary with the frequency and the direction of vibration so as to predict the vibration isolation efficiency of a seat. The SEAT value is mostly used to select seat cushions or seat suspensions based on the transmission of vertical vibration to the principal supporting surface of a seat. This study investigated the accuracy of SEAT values in predicting how seats with backrests influence the discomfort caused by multiple-input vibration. Twelve male subjects participated in a four-part experiment to determine equivalent comfort contours, the relative discomfort, the location of discomfort, and seat transmissibility with three foam seats and a rigid reference seat at 14 frequencies of vibration in the range 1–20 Hz at magnitudes of vibration from 0.2 to 1.6 ms −2 r.m.s. The ‘measured seat dynamic discomfort’ (MSDD) was calculated for each foam seat from the ratio of the vibration acceleration required to cause similar discomfort with the foam seat and with the rigid reference seat. Using the frequency weightings in current standards, the SEAT values of each seat were calculated from the ratio of overall ride values with the foam seat to the overall ride values with the rigid reference seat, and compared to the corresponding MSDD at each frequency. The SEAT values provided good predictions of how the foam seats increased vibration discomfort at frequencies around the 4-Hz resonance but reduced vibration discomfort at frequencies greater than about 6.3 Hz, with discrepancies explained by a known limitation of the frequency weightings. [ABSTRACT FROM AUTHOR]

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an exceedingly rare subtype of pancreatic ductal adenocarcinoma. Histologically, UC-OGC is characterized by three cell types namely, a neoplastic mononuclear cell component, non-neoplastic osteoclast-like giant cells, and a non-neoplastic mononuclear histiocytic component. The behavior of this tumor is unpredictable; but many patients survive many years after diagnosis. UC-OGC may have a better prognosis compared to conventional pancreatic adenocarcinoma due to its slower local spread, less aggressive nature, better response to surgical resection and/or chemotherapy, and fewer metastases. Due to likely differences in prognosis and significant impact on patient management, it is important to distinguish this subtype from other types of pancreatic adenocarcinoma. We report a case of a small (<1 cm) undifferentiated carcinoma with osteoclast-like giant cells of the posterior pancreatic body discovered incidentally on magnetic resonance image (MRI) scan of a middle-aged man. The radiologic and pathologic findings are presented along with a discussion of the differential diagnosis of this exceedingly rare entity. • Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is a rare subtype of pancreatic ductal adenocarcinoma. • Characteristic components include: neoplastic cells, and non-neoplastic osteoclast-like giant cells and mononuclear histiocytes. • UC-OGC may have a better prognosis compared to conventional pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The affinity constants of a ligand for active and inactive states of a receptor ultimately determine its capacity to activate downstream signaling events. In this report, we describe a reverse-engineering strategy for estimating these microscopic constants. Methods: Our approach involves analyzing responses measured downstream in the signaling pathway of a G protein-coupled receptor under conditions of allosteric modulation and reduced receptor expression or partial receptor inactivation. The analysis also yields estimates of the isomerization constant of the unoccupied receptor, the sensitivity constant of the signaling pathway, and the more empirical parameters of the receptor population including the observed affinities and efficacies of allosteric and orthosteric ligands – including inverse agonists – and the efficacy of the unoccupied receptor (i.e., constitutive activity). Results and discussion: We validate our approach with an analytical proof and by analysis of simulated data. We also use our method to analyze data from the literature. We show that the values of the microscopic constants of orthosteric and allosteric ligands are constant regardless of the allosteric interaction and the nature of the receptor-signaling pathway as long as the same active state mediates the response. Our analysis is useful for quantifying probe-dependent allosteric interactions and the selectivity of agonists for different signaling pathways. Knowing the isomerization constant and sensitivity constant of a signaling pathway in a given cell line or tissue preparation enables future investigators to estimate the affinity constants of agonists for receptor states simply through analysis of their concentration–response curves. Our approach also provides a means of validating in silico estimates of ligand affinity for crystal structures of active and inactive states of the receptor. [Copyright &y& Elsevier]

Abstract: Previous research has suggested that faces and words are processed and remembered differently as reflected by different ERP patterns for the two types of stimuli. Specifically, face stimuli produced greater late positive deflections for old items in anterior compared to posterior regions, while word stimuli produced greater late positive deflections in posterior compared to anterior regions. Given that words have existing representations in subjects׳ long-term memories (LTM) and that face stimuli used in prior experiments were of unknown individuals, we conducted an ERP study that crossed face and letter stimuli with the presence or absence of a prior (stable or existing) memory representation. During encoding, subjects judged whether stimuli were known (famous face or real word) or not known (unknown person or pseudo-word). A surprise recognition memory test required subjects to distinguish between stimuli that appeared during the encoding phase and stimuli that did not. ERP results were consistent with previous research when comparing unknown faces and words; however, the late ERP pattern for famous faces was more similar to that for words than for unknown faces. This suggests that the critical ERP difference is mediated by whether there is a prior representation in LTM, and not whether the stimulus involves letters or faces. [Copyright &y& Elsevier]

Abstract: While walking on an instrumented treadmill, 20 subjects were perturbed by lateral sinusoidal oscillations representative of those encountered in transport: frequencies in the range 0.5–2 Hz and accelerations in the range 0.1–2.0 ms−2 r.m.s., corresponding to velocities in the range 0.032–0.16 ms−1 r.m.s. Postural stability was assessed from the self-reported probability of losing balance (i.e., perceived risk of falling) and the movements of the centre of pressure beneath the feet. With the same acceleration at all frequencies, the velocities and displacements of the oscillatory perturbations were greater with the lower frequency oscillations, and these caused greater postural instability. With the same velocity at all frequencies, postural instability was almost independent of the frequency of oscillation. Movements of the centre of pressure show that subjects attempted to compensate for the perturbations by increasing their step width and increasing their step rate. [Copyright &y& Elsevier]

Abstract: The method of magnitude estimation is used in psychophysical studies to obtain numerical values for the intensity of perception of environmental stresses (e.g., noise and vibration). The exponent in a power function relating the subjective magnitude of a stimulus (e.g., the degree of discomfort) to the physical magnitude of the stimulus shows the rate of growth of sensations with increasing stimulus magnitude. When judging noise and vibration, there is no basis for deciding whether magnitude estimation should be performed with a reference stimulus (i.e., relative magnitude estimation, RME) or without a reference stimulus (i.e., absolute magnitude estimation, AME). Twenty subjects rated the discomfort caused by thirteen magnitudes of whole-body vertical vibration and 13 levels of noise, by both RME and AME on three occasions. There were high correlations between magnitude estimates of discomfort and the magnitudes of vibration and noise. Both RME and AME provided rates of growth of discomfort with high consistency over the three repetitions. When judging noise, RME was more consistent than AME, with less inter-subject variability in the exponent, n s. When judging vibration, RME was also more consistent than AME, but with greater inter-subject variability in the exponent, n v. When judging vibration, AME may be beneficial because sensations caused by the RME reference stimulus may differ (e.g., occur in a different part of the body) from the sensations caused by the stimuli being judged. [Copyright &y& Elsevier]

EBF1 plays a crucial role in early adipogenesis; however, despite high expression in mature adipocytes, its function in these cells is currently unknown. To identify direct and indirect EBF1 targets in fat, we undertook a combination of transcriptional profiling of EBF1-deficient adipocytes and genome-wide EBF1 location analysis. Our results indicate that many components of metabolic and inflammatory pathways are positively and directly regulated by EBF1, including PI3K/AKT, MAPK, and STAT1 signaling. Accordingly, we observed significant reduction ofmultiple signaling events in EBF1 knockdown cells as well as a reduction in insulin-stimulated glucose uptake and lipogenesis. Inflammatory signaling, gene expression, and secretion of inflammatory cytokines were also significantly affected by loss of EBF1 in adipocytes, although ChIP-sequencing results suggest that these actions are indirect.We also found that EBF1 occupies some 35,000 sites in adipocytes, most of which occur in enhancers. Significantly, comparison with three other published EBF1 ChIP-sequencing data sets in B-cells reveals both gene- and cell type-specific patterns of EBF1 binding. These results advance our understanding of the transcriptional mechanisms regulating signaling pathways in mature fat cells and indicate that EBF1 functions as a key integrator of signal transduction, inflammation, and metabolism. [ABSTRACT FROM AUTHOR]

Abstract: Thresholds for the perception of vibration on the hand reduce with increasing area of excitation when the thresholds are mediated by the Pacinian channel (a phenomenon known as spatial summation) but thresholds are generally independent of the area of excitation when they are mediated by non-Pacinian channels. The effect of the area of excitation on vibrotactile thresholds at the sole of the foot has not been thoroughly investigated. In the study reported in this paper, thresholds for the perception of 20Hz vibration and 160Hz vibration were determined on the foot (at the big toe (hallux), the medial (inside) ball, the lateral (outside) ball, and the heel) and on the hand (at the thenar eminence and at the fingertip) in 12 male subjects using four probe diameters: 1mm (0.19cm2 excitation area), 3mm (0.38cm2), 6mm (0.78mm2) and 10mm (1.53cm2) with a 2mm gap between the vibrating probe and a fixed surround. On both the hand and the foot, thresholds for the perception of 160Hz vibration decreased as the probe diameter increased. There was no overall consistent change in thresholds for the perception of 20Hz vibration. Thresholds for the perception of 160Hz vibration were lowest at the fingertip and highest at the big toe. Thresholds for 20Hz vibration were also lowest at the fingertip. It is concluded that on the sole of the foot there is evidence of spatial summation in the perception of 160Hz vibration, mediated by the Pacinian channel, but not in the perception of 20Hz vibration, mediated by a non-Pacinian channel. The findings show that vibrotactile thresholds at the foot obtained with different areas of excitation, or an unknown area of excitation, should not be compared. It is concluded that there is a need to standardise methods of measuring the vibrotactile thresholds at the foot that are obtained for clinical applications. [Copyright &y& Elsevier]

Ribulose-bisphosphate carboxylase/oxygenase (Rubisco) activase uses the energy from ATP hydrolysis to remove tight binding inhibitors from Rubisco, thus playing a key role in regulating photosynthesis in plants. Although several structures have recently added much needed structural information for different Rubisco activase enzymes, the arrangement of these subunits in solution remains unclear. In this study, we use a variety of techniques to show that Rubisco activase forms a wide range of structures in solution, ranging from monomers to much higher order species, and that the distribution of these species is highly dependent on protein concentration. The data support a model in which Rubisco activase forms an open spiraling structure rather than a closed hexameric structure. At protein concentrations of 1 μM, corresponding to the maximal activity of the enzyme, Rubisco activase has an oligomeric state of 2-4 subunits. We propose a model in which Rubisco activase requires at least 1 neighboring subunit for hydrolysis of ATP. [ABSTRACT FROM AUTHOR]

Abstract: Lateral acceleration causes discomfort but how the discomfort depends on the frequency of acceleration or characteristics of seating is poorly understood. Using magnitude estimation, twelve male subjects rated the discomfort caused by lateral oscillation at eight frequencies (0.2–1.0 Hz) across four seating conditions (a rigid seat and a train seat, both with and without backrests). Discomfort increased with increasing frequency of lateral acceleration in a similar manner for all four seating conditions. However, at all frequencies and with both seats there was less discomfort when sitting with backrest support than without. Least discomfort occurred on the train seat with backrest and greatest discomfort on the rigid seat without backrest. Current standards predict an additive effect of backrest on vibration discomfort, but the findings show that low frequency lateral acceleration can cause less discomfort when sitting with a backrest than when sitting on the same seat without a backrest. [Copyright &y& Elsevier]

Abstract: With the possibility of future fresh water shortages increasing, a methodology that incorporates climatic and anthropogenic factors is needed. This research estimates future water availability in the Lower Cape Fear basin using changes in climate, land use, and population growth. The USGS Thornthwaite monthly water balance model is used with estimates of climate change and land use change parameters to assess future water resources based on predicted monthly fluxes of the water balance. The southern United States is a rapidly growing region. Trends present in the population data are used to produce future estimates of population for the basin. Precipitation and temperature estimates based on Intergovernmental Panel on Climate Change (IPCC) predictions and current climatology are inputs to the model. Projected increases in impervious surface cover due to population growth and urbanization are incorporated through the model runoff factor. Water stress indicators are used to categorize the sub-watersheds as water rich, water stressed, or water scarce. Scenarios incorporating regional predictions of climate change indicate a decrease in summer soil moisture minima and increases in summer water deficits. Ensemble runs indicate a shift toward water stress in the Lower Cape Fear River basin, due to a warming climate as well as increased demand. While climate change has a significant impact on water resources, population growth was found to have the most substantial impact. The methods and findings have application to water managers at local and regional levels. [Copyright &y& Elsevier]

Abstract: Current methods for evaluating seat vibration to predict vibration discomfort assume the same frequency weightings and axis multiplying factors can be used at the seat surface and the backrest irrespective of the backrest inclination. This experimental study investigated the discomfort arising from whole-body vertical vibration when sitting on a rigid seat with no backrest and with a backrest inclined at 0° (upright), 30°, 60°, and 90° (recumbent). Within each of these five postures, 12 subjects judged the discomfort caused by vertical sinusoidal whole-body vibration (at frequencies from 1 to 20 Hz at magnitudes from 0.2 to 2.0 m s−2 r.m.s.) relative to the discomfort produced by a reference vibration (8 Hz at 0.4 m s−2 r.m.s.). With 8-Hz vertical vibration, the subjects also judged vibration discomfort with each backrest condition relative to the vibration discomfort with no backrest. The locations in the body where discomfort was experienced were determined for each frequency at two vibration magnitudes. Equivalent comfort contours were determined for the five conditions of the backrest and show how discomfort depends on the frequency of vibration, the presence of the backrest, and the backrest inclination. At frequencies greater than about 8 Hz, the backrest increased vibration discomfort, especially when inclined to 30°, 60°, or 90°, and there was greater discomfort at the head or neck. At frequencies around 5 and 6.3 Hz there was less vibration discomfort when sitting with an inclined backrest. [Copyright &y& Elsevier]

Abstract: Few studies have compared the discomfort caused by vibration in different directions, and few have investigated the vibration discomfort of standing people. This study was designed to compare the discomfort experienced by standing people exposed to sinusoidal vibration in the fore-and-aft, lateral, and vertical directions. Using the method of magnitude estimation, 12 subjects estimated the discomfort caused by 4-Hz sinusoidal vibration at 10 different magnitudes. At 4 Hz, subjects were less sensitive to lateral vibration than to fore-and-aft vibration (Ky /Kx  = 0.71), and more sensitive to vertical vibration than to horizontal vibration (Kz /Kx  = 1.95; Kz /Ky  = 2.77). Previous findings showing how the discomfort of standing people depends on the frequency of fore-and-aft, lateral, and vertical vibration were used to define frequency weightings that reflect relative sensitivity to vibration in each direction. The frequency weightings differ from those appropriate for seated people, and differ from the weightings for standing people in current standards that were mostly derived from understanding of the discomfort of seated people. [Copyright &y& Elsevier]

Abstract: When using vibrotactile thresholds to investigate neuropathy in the fingers, the indentation of a vibrating probe, and the force applied to a static surround around a vibrating probe, affect thresholds. This study was designed to investigate the effects on vibrotactile perception thresholds at the sole of the foot of probe indentation (i.e. height of a vibrating probe relative to a static surround) and the force applied to the static surround. Thresholds at 20Hz (expected to be mediated by the NP I channel) and at 160Hz (expected to be mediated by the Pacinian channel) were obtained at the hallux (i.e. greater toe) and the ball of the foot on 14 healthy subjects. In one condition, the height of the vibrating probe was varied to 0, 1, 2, 3, and 4mm above a static surround with 4-N force applied to the surround. In a second condition, the force applied to the surround was varied to 1, 2, 3, 4, 5, and 6N while using a probe height of 1mm. Thresholds at 20Hz decreased with increasing probe height from 0 to 1mm but showed no significant variation between 2, 3, and 4mm at either the hallux or the ball of the foot. Thresholds at 160Hz decreased with increasing probe height from 0 to 4mm at both the hallux and the ball of the foot. Thresholds at 20Hz obtained with 1-N surround force were higher than thresholds obtained with 2N, but there was no significant difference with surround forces from 2 to 6N at either the hallux or the ball of the foot. Thresholds at 160Hz were unaffected by variations in surround force at the ball of the foot but tended to decrease with increasing force at the hallux. It is concluded that a vibrating probe flush with a static surround, and a surround force in the range 2–4N, are appropriate when measuring vibrotactile thresholds at the hallux and the ball of the foot with a 6-mm diameter contactor and a 2-mm gap to the static surround. [Copyright &y& Elsevier]

Abstract: Objectives: : Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity). In addition, chemically modified serum components that contribute to serum ThT fluorescence were explored and identified. Design, Methods, and Results: : Sera from 105 people, including 35 healthy subjects, and 70 high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT fluorescence. Although mean (±SD) ThT fluorescence did not differ significantly between groups (controls 0.97±0.26, RA 1.12±0.45, and SLE 0.74±0.23), the combined data set showed significant inverse correlation (p =0.046) between ThT fluorescence tertiles and small artery elasticity. Correlation was also found between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C-reactive protein. Floatation fractionation of apoB containing lipoproteins showed that ThT reactivity in this fraction correlated with both serum oxidised-LDL and LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was associated with the non-apoB containing serum fraction, with the majority of ThT fluorescence associated with albumin. Incubation of purified albumin with glucose or with methylglyoxal induced ThT fluorescence, suggesting that glycated or chemical adducts of albumin contribute to the variation in ThT fluorescence of human serum. Conclusions: : We propose that the detection of these adducts in serum using ThT fluorescence measurements may provide a marker for chemically modified protein structures that could assist the assessment of cardiovascular disease risk. [Copyright &y& Elsevier]

Abstract: We report the synthesis of (2E,5E)-4-oxoheptadienedioic acid and (2E)-4-oxoheptenedioic acid and evaluation of both diester and diacid analogues as inhibitors of bacterial dihydrodipicolinate synthase. Enzyme kinetic studies allowed the determination of second-order rate constants of inactivation; and substrate co-incubation studies have shown the inhibitors act at the active-site. Mass spectrometric analyses have further explored the enzyme–inhibitor interaction and determined the sites of enzyme alkylation. [Copyright &y& Elsevier]

To understand the molecular mechanisms underlying transcriptional activation of fatty-acid synthase (FAS), we examined the relationship between upstream stimulatory factor (USF) and SREBP-1c, two transcription factors that we have shown previously to be critical for FAS induction by feeding/insulin. Here, by using a combination of tandem affinity purification and coimmunoprecipitation, we demonstrate, for the first time, that USF and SREBP-1 interact in vitro and in vivo. Glutathione S-transferase pulldown experiments with various USF and sterol regulatory element-binding protein (SREBP) deletion constructs indicate that the basic helix-loop-helix domain of USF interacts directly with the basic helix-loop-helix and an N-terminal region of SREBP-1c. Furthermore, cotransfection of USF and SREBP-1c with an FAS promoter-luciferase reporter construct in Drosophila SL2 cells results in highly synergistic activation of the FAS promoter. We also show similar cooperative activation of the mitochondrial glycerol-3-phosphate acyltransferase promoter by USF and SREBP-1c. Chromatin immunoprecipitation analysis of mouse liver demonstrates that USF binds constitutively to the mitochondrial glycerol 3-phosphate acyltransferase promoter during fasting/refeeding in vivo, whereas binding of SREBP-1 is observed only during refeeding, in a manner identical to that of the FAS promoter. In addition, we show that the synergy we have observed depends on the activation domains of both proteins and that mutated USF or SREBP lacking the N-terminal activation domain could inhibit the transactivation of the other. Closely positioned E-boxes and sterol regulatory elements found in the promoters of several lipogenic genes suggest a common mechanism of induction by feeding/insulin. [ABSTRACT FROM AUTHOR]

Abstract: Opinions vary on the generalizability of empirically supported treatments to diverse populations in naturalistic settings and on the relative merits of delivering treatments through interpreters. The authors present statistical analyses of outcome data from a community mental health program that served foreign-born refugees resettled in the U.S. The program used a manualized, empirically supported treatment, Cognitive Processing Therapy, to address symptoms of PTSD in this population. Participants received psychological treatment in native languages either with a therapist who spoke their language or with a therapist who used an interpreter. Results demonstrated that treatment of PTSD was highly effective whether delivered directly or through an interpreter. [Copyright &y& Elsevier]

Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) mediates the first unique reaction of (S)-lysine biosynthesis in plants and microbes—the condensation of (S)-aspartate-β-semialdehyde ((S)-ASA) and pyruvate. It has been shown that DHDPS is partially feedback inhibited by (S)-lysine; it is suggested that this mechanism regulates flux through the DAP biosynthetic pathway. Others have characterised DHDPS from Escherichia coli with respect to (S)-lysine inhibition. They have concluded that, with respect to pyruvate, the first substrate of the reaction, DHDPS shows uncompetitive inhibition: as such, they further suggest that (S)-lysine inhibits DHDPS via interaction with the binding site for the second substrate, (S)-ASA. Yet, this finding is based on the assumption that (S)-lysine is a fully uncompetitive inhibitor. In light of crystallographic studies, which lead to the proposal that (S)-lysine affects the putative proton-relay of DHDPS, we re-evaluated the inhibition mechanism of DHDPS with respect to (S)-lysine by incorporating the observed hyperbolic inhibition. Our data showed that lysine is not an uncompetitive inhibitor, but a mixed inhibitor when pyruvate and (S)-lysine concentrations were varied. Thus, consistent with the crystallographic data, (S)-lysine must have an effect on the initial steps of the DHDPS reaction, including the binding of pyruvate and Schiff base formation. [Copyright &y& Elsevier]

We compared the binding properties of selective muscarinic antagonists with their potencies for antagonizing muscarinic responses in Chinese hamster ovary (CHO) cells expressing M2 and M3 muscarinic receptors in combination and in isolation. When measured by the competitive displacement of [3H]N-methylscopolamine binding to CHO cells expressing both M2 and M3 muscarinic receptors (CHO M2+M3 cells), the competition curves of the subtype-selective muscarinic antagonists were consistent with a two-site model. One site exhibited binding properties identical to those of CHO M2 cells, whereas the other site exhibited properties like those of CHO M3 cells. Oxotremorine-M, a muscarinic agonist, elicited a robust, pertussis toxin-insensitive stimulation of phosphoinositide hydrolysis in both CHO M3 and CHO M2+M3 cells, but not in CHO M2 cells. The pharmacological antagonism of the phosphoinositide response exhibited similar properties in both CHO M3 and CHO M2+M3 cells. Oxotremorine-M elicited a pertussis toxin-sensitive, robust inhibition of forskolin-stimulated cyclic AMP (cAMP) accumulation in both CHO M2 and CHO M2+M3 cells and a less robust inhibition in CHO M3 cells. At higher concentrations, oxotremorine-M elicited an increase in cAMP accumulation over the maximal inhibition noted at lower concentrations in both CHO M3 and CHO M2+M3 cells. Following pertussis toxin treatment, only the stimulatory phase of the cAMP response to oxotremorine-M was observed in CHO M2, CHO M3, and CHO M2+M3 cells. The pharmacological antagonism of the cAMP response in CHO M2+M3 cells resembled that expected for a response mediated independently by both M2 and M3 receptors. [Copyright &y& Elsevier]

We tested the utility of the heart rate response as an indicator of emotional processing in prolonged exposure therapy for a female rape victim. Physiological data, for the first and the last available imaginal exposure to the rape, showed that the heart rate response was a useful index of successful activation and habituation of fear structures during therapy. The results suggest that the heart rate response may provide an objective and unbiased assessment of emotional processing that is not dependent on either self-report or interviewer-based assessments. [Copyright &y& Elsevier]