PTMSearchPlus: software tool for automated protein identification and post-translational modification characterization by integrating accurate intact protein mass and bottom-up mass spectrometric data searches.
PTMSearchPlus is a software tool for the automated integration of accurate intact protein mass (AIPM) and bottom-up (BU) mass spectra searches/data in order to both confidently identify the intact proteins and to characterize their post-translational modifications (PTMs). The development of PTMSearchPlus was motivated by the desire to effectively integrate high-resolution intact protein molecular masses with bottom-up peptide MS/MS data. PTMSearchPlus requires as input both intact protein and proteolytic peptide mass spectra collected from the same protein mixture, a FASTA protein database, and a selection of possible PTMs, the types and ranges of which can be specified. The output of PTMSearchPlus is a list of intact and modified proteins matching the AIPM data concomitant with their respective peptides found by the BU search. This list also contains protein and peptide sequence coverage information, scores, etc. that can be used for further evaluation or refiltering of the results. Corresponding and annotated AIPM and BU mass spectra are also displayed for visual inspection when a listed protein or a peptide is selected. These and other controls ensure that the user can manually evaluate, modify (e.g., remove obvious false positives, low quality spectra etc.), and save the results of the automated search if necessary. Driven by the exponential growth in the number of possible peptide candidates in a BU search when multiple PTMs are probed, the advantages on search speed by limiting the total number of possible PTMs on a peptide in the BU search or by performing an "AIPM predicted" BU search are also discussed in addition to the integration approach. The features of PTMSearchPlus are demonstrated using both a protein standard mixture and a complex protein mixture from Escherichia coli. Experimental data revealed a unique advantage of coupling AIPM and the BU data sets that is mutually beneficial for both approaches. Namely, AIPM data can confirm that no PTM peptides were missed in a BU search, while the BU search determines the location of the PTM. This information is not available using an AIPM search alone.


Probing proton dissociation in ionic polymers by means of in situ ATR-FTIR spectroscopy.
The hydration process of cationic membrane protogenic groups was investigated using in situ ATR-FTIR spectroscopy. The aim of this study is to provide a relationship between the hydration degree of the membrane and the dissociation state of exchange sites inside the polymer material. IR spectra were recorded by means of an environmental device specifically manufactured to allow the control of water vapour pressure in equilibrium with the sample. The behaviour of Nafion 112 and sulfonated poly(ether ether ketone) (S-PEEK), in both proton and sodium forms, was compared. IR data, analyzed and fitted in the 800-1850 cm(-1) spectral range, gave precise information on the assignment of sulfonic group vibrational modes. The results of this study improve the understanding of the transition phenomena between dissociated and undissociated states of the grafted sites in protonic conductors.


Overview of the Neurolab Spacelab mission.
Neurolab is a NASA Spacelab mission with multinational cooperative participation that is dedicated to research on the nervous system. The nervous systems of all animal species have evolved in a one-g environment and are functionally influenced by the presence of gravity. The absence of gravity presents a unique opportunity to gain new insights into basic neurologic functions as well as an enhanced understanding of physiological and behavioral responses mediated by the nervous system. The primary goal of Neurolab is to expand our understanding of how the nervous system develops, functions in, and adapts to microgravity space flight. Twenty-six peer reviewed investigations using human and nonhuman test subjects were assigned to one of eight science discipline teams. Individual and integrated experiments within these teams have been designed to collect a wide range of physiological and behavior data in flight as well as pre- and postflight. Information from these investigations will be applicable to enhancing the well being and performance of future long duration space travelers, will contribute to our understanding of normal and pathological functioning of the nervous system, and may be applied by the medical community to enhance the health of humans on Earth.


Effects of arterial oxygen content on peripheral locomotor muscle fatigue.
The effect of arterial O2 content (Ca(O2)) on quadriceps fatigue was assessed in healthy, trained male athletes. On separate days, eight participants completed three constant-workload trials on a bicycle ergometer at fixed workloads (314 +/- 13 W). The first trial was performed while the subjects breathed a hypoxic gas mixture [inspired O2 fraction (Fi(O2)) = 0.15, Hb saturation = 81.6%, Ca(O2) = 18.2 ml O2/dl blood; Hypo] until exhaustion (4.5 +/- 0.4 min). The remaining two trials were randomized and time matched with Hypo. The second and third trials were performed while the subjects breathed a normoxic (Fi(O2) = 0.21, Hb saturation = 95.0%, Ca(O2) = 21.3 ml O2/dl blood; Norm) and a hyperoxic (Fi(O2) = 1.0, Hb saturation = 100%, Ca(O2) = 23.8 ml O2/dl blood; Hyper) gas mixture, respectively. Quadriceps muscle fatigue was assessed via magnetic femoral nerve stimulation (1-100 Hz) before and 2.5 min after exercise. Myoelectrical activity of the vastus lateralis was obtained from surface electrodes throughout exercise. Immediately after exercise, the mean force response across 1-100 Hz decreased from preexercise values (P < 0.01) by -26 +/- 2, -17 +/- 2, and -13 +/- 2% for Hypo, Norm, and Hyper, respectively; each of the decrements differed significantly (P < 0.05). Integrated electromyogram increased significantly throughout exercise (P < 0.01) by 23 +/- 3, 10 +/- 1, and 6 +/- 1% for Hypo, Norm, and Hyper, respectively; each of the increments differed significantly (P < 0.05). Mean power frequency fell more (P < 0.05) during Hypo (-15 +/- 2%); the difference between Norm (-7 +/- 1%) and Hyper (-6 +/- 1%) was not significant (P = 0.32). We conclude that deltaCa(O2) during strenuous systemic exercise at equal workloads and durations affects the rate of locomotor muscle fatigue development.


Case reports: trimethoprim-sulfamethoxazole-induced meningitis in patients with HIV infection.
Meningitis is a frequent complication of the human immunodeficiency infection. Possible causes include bacterial, fungal, mycobacterial, syphilitic, and vital pathogens (including the human immunodeficiency virus). Drugs must also be considered in the differential diagnosis. Two patients with probable trimethoprim-sulfamethoxazole-induced meningitis are described in the setting of human immunodeficiency virus infection.


Genomic imprinting of human p57KIP2 and its reduced expression in Wilms' tumors.
p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP2 is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome (BWS), a cancer syndrome, making it a tumor suppressor candidate. Several types of childhood tumors including Wilms' tumor, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the familial BWS has indicated maternal carriers and suggested a role in genomic imprinting. Previously, we demonstrated that p57KIP2 is imprinted in the mouse. Here we describe the genomic imprinting of human p57KIP2 and the reduction of its expression in Wilms' tumors. High resolution mapping locates p57KIP2 in the region responsible for both tumor suppressivity and BWS.


Neuroleptic-free intervals in the treatment of schizophrenia.
During a period of 1-2 1/2 years the neuroleptic regimen of 14 schizophrenic outpatients was interrupted every 6 months by drug holidays of 6 weeks' duration. As a result, 10 patients achieved a substantially reduced maintenance dose. The authors were unable to predict for whom the drug holidays would be safe.


[Prognoses of acute encephalopathy].
We investigated the prognoses of 103 children with acute encephalopathy at more than one year from the onset. The patients were divided into five groups according to the clinical courses during the acute stage;group 1:1 case with metabolic disorder, group, 2:24 with cytokine storms, group, 3:68 with prolonged convulsion more than 30 minutes, group, 4:5 with severe refractory status epilepticus, and group, 5:5 with the main symptom of impaired consciousness. We checked the past histories, etiologies, severities of consciousness loss, complications and disabilities including higher cortical dysfunction in their medical charts. The average age of onset in all cases was 3 years, with the highest age of 6 years 5 months in group 4. Regarding the past histories, febrile seizures, asthma and theophylline medication were prominent though they were not significantly different. Regarding etiologies, influenza infection, 36 cases, and HHV-6 infection, 7 cases, were prominent though they were not significantly different. Complicating disabilities comprised mental retardation, 89.3%, higher cortical dysfunction, 77.7%, epilepsies, 68.9%, and motor disturbance, 27.2%. The severity of disabilities increased in the order of 1, 2, 3, 4, 5. Attention deficit and visiospacial disturbance were the main symptoms of higher cortical dysfunction.


Residential caregiver attitudes toward seriously mentally ill persons.
Previous research has found that caregiver attitudes are associated with the course of illness of seriously mentally ill (SMI) persons. This study examined whether variation in caregiver attitudes could be accounted for by (a) staff caregivers and/or (b) SMI persons. Group home staff were asked to describe each SMI group home resident and to describe the relationship they had with each resident. We recorded the number of positive and negative statements made by each staff member about each resident's character, behaviors, and the interactions staff had with them. Overall, the variation in positive staff statements about group home residents was significantly accounted for by the residents. In general, the variation in negative staff statements was significantly accounted for by staff. However, the variation in negative staff statements about the character of residents was accounted for by both staff and residents.


Allosteric modulators for adenosine receptors: an alternative to the orthosteric ligands.
Adenosine is a ubiquitous homeostatic substance which exerts its action by triggering four different cell membrane G protein-coupled receptors, classified as A(1), A(2A), A(2B), and A(3). Being widely distributed and deeply involved in several physiological functions, as well as pathological disorders, these receptors represent an excellent drug target and the development of specific ligands has been tested as a promising therapeutic concept. Among the obtainable ligands, allosteric modulators offer higher advantages with respect to classical orthosteric compounds, as they possible to achieve greater selectivity and better modulatory control at disease mediating receptors. Actually, synergizing with adenosine bound to the primary binding site, these compounds may modify receptor functions through interaction with an additional binding site. As a consequence, their actions depend directly on the release of the endogenous agonist. A number of compound have been developed as effective allosteric modulators. Most of them target adenosine A(1) and A(3) receptor subtypes as, to date, little or no research attempt have been made to improve the field of A(2A) and A(2B) ligands. This review updates literature on the allosteric modulators that has appeared in the last few years, focusing its attention on medicinal chemistry, in terms of chemical structure and structure-activity relationships. This will provide new perspectives on existing data and an exciting starting point for the development of novel and more effective modulators.


Sex pheromone communication in the screwworm,Cochliomyia hominivorax: Ontogenetic and strain effects.
A laboratory behavioral assay was used to examine ontogenetic and strain effects on sex pheromone production and reception in the screwworm, which employs a female-produced contact pheromone to stimulate male copulatory attempts. Pheromone levels peaked between three and six days after adult emergence in females of two strains that had been colonized fewer than 50 generations. Pheromone was detectable at low levels in newly emerged flies of both sexes but disappeared from males by two days of age, when males first became responsive to females. A similar decline in pheromone with ontogenetic age was previously described for females of a strain colonized over 100 generations. Interstrain tests between the two newer strains, which differed by 35 generations in duration of colonization, demonstrated lower female pheromone activity but higher male responsiveness to pheromone in the older strain, despite the similar shape within these strains of curves relating female age and pheromone activity. The data suggest that conditions of screwworm colonization result in gradual loss of the pheromone peak that develops three to six days after emergence in newly colonized females. Higher male responsiveness associated with longer colonization involved change in both thresholds and dose dependency and may be relevant to control of the screwworm via the sterile insect technique.


Measurement of pulmonary CO2 elimination must exclude inspired CO2 measured at the capnometer sampling site.
The pulmonary elimination of the volume of CO2 per breath (VCO2/br, integration of product of airway flow (V) and PCO2 over a single breath) is a sensitive monitor of cardio-pulmonary function and tissue metabolism. Negligible inspired PCO2 results when the capnometry sampling site (SS) is positioned at the entry of the inspiratory limb to the airway circuit. In this study, we test the hypothesis that moving SS lungward will result in significant inspired CO2 (VCO2[I]), that needs to be excluded from VCO2/br. We ventilated a mechanical lung simulator with tidal volume (VT) of 800 mL at 10 breaths/min. CO2 production, generated by burning butane in a separate chamber, was delivered to the lung. Airway V and PCO2 were measured (Capnomac Ultima, Datex), digitized (100 Hz for 60 s), and stored by microcomputer. Then, computer algorithms corrected for phase differences between V and PCO2 and calculated expired and inspired VCO2 (VCO2[E] and VCO2[I]) for each breath, whose difference equalled overall VCO2/br. The lung and Y-adapter (where the inspiratory and expiratory limbs of the circuit joined) were connected by the SS and a connecting tube in varying order. During ventilation of the lung model (VT = 800 ml) with SS adjacent to the inspiratory limb, VCO2[E] was 16.8 +/- 0.4 ml and VCO2[I] was 1.1 +/- 0.1 ml, resulting in overall VCO2/br (VCO2[E] - VCO2[I]) of 15.7 +/- 0.4 ml. If VCO2[I] was ignored in the determination of VCO2/br, then the %error that VCO2[E] overestimated VCO2/br was 7.2 +/- 0.3%. This %error significantly increased (p < 0.05, Student's t-test) when VT was decreased to 500 mL (%error = 12.4 +/- 0.8%) or when SS was moved to the lungward side of a 60 mL connecting tube (VCO2[I] = 2.8 +/- 0.2, %error = 18.2 +/- 1.6) or a 140 mL tube (VCO2[I] = 5.9 +/- 0.3 mL, %error = 37.5 +/- 3.3). When the SS was moved lungward from the inspiratory limb, instrumental dead space (VDINSTR) increased and, at end-expiration, contained exhaled CO2 from the previous breath. During the next inspiration, this CO2 was rebreathed relative to SS (i.e. VCO2[I]), and contributed to VCO2[E]. Thus, VCO2[E] overestimated VCO2/br (%error) by the amount of rebreathing, which was exacerbated by larger VDINSTR (increased VCO2[I]) or smaller VT (increased VCO2[I]-to-VCO2/br ratio).


Paranasal sinus lymphoma: Retrospective review with focus on clinical features, histopathology, prognosis, and relationship to systemic lymphoma.
Paranasal sinus lymphoma is a rare clinical entity. We conducted a retrospective case series of 68 patients with biopsy-confirmed paranasal sinus lymphoma with attention on systemic disease association. Of 63 patients with paranasal sinus lymphoma, 35 (56%) had systemic involvement. Four patient groups were identified: (1) primary paranasal sinus lymphoma (44%); (2) systemic disease occurring concurrently with paranasal sinus lymphoma (25%); (3) paranasal sinus lymphoma with relapse of preexisting systemic lymphoma (22%); and (4) progression to systemic disease after primary paranasal sinus lymphoma (8%). Most of the patients with systemic disease were diagnosed at 50 + years and had positive smoking histories. There was a trend toward disease activity in the neighboring ocular location. For patients with preexisting systemic lymphoma, the mean time to paranasal sinus lymphoma was 65 months. When systemic lymphoma developed after localized paranasal sinus lymphoma, mean time to progression was 23 months. Diffuse large B cell lymphoma was the most common paranasal sinus lymphoma. There is a risk of systemic involvement during the disease course of paranasal sinus lymphoma. Biopsy is the preferred first management step and should precede debulking or mass resection in nonemergent cases. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1065-1070, 2017.


Ablation of facial scars by programmed dermabrasion.
Revisions of scars, characteristically deferred for 6 to 12 months after wounds have healed, are performed to improve function and appearance. However, none of the techniques that has evolved to modify cicatrical deformities has afforded total, permanent effacement of scars already present. Evidence is presented here that dermabrasion of both surgical and accidental scars of the face, done 4 to 8 weeks after the primary wound, usually eliminates visible residual cicatrization.


Prediction of Groundwater Level in Ardebil Plain Using Support Vector Regression and M5 Tree Model.
The Ardebil plain, which is located in northwest Iran, has been faced with a recent and severe decline in groundwater level caused by a decrease of precipitation, successive long-term droughts, and overexploitation of groundwater for irrigating the farmlands. Predictions of groundwater levels can help planners to deal with persistent water deficiencies. In this study, the support vector regression (SVR) and M5 decision tree models were used to predict the groundwater level in Ardebil plain. The monthly groundwater level data from 24 piezometers for a 17-year period (1997 to 2013) were used for training and test of models. The model inputs included the groundwater levels of previous months, the volume of entering precipitation into every cell, and the discharge of wells. The model output was the groundwater level in the current month. In order to evaluate the performance of models, the correlation coefficient (R) and the root-mean-square error criteria were used. The results indicated that both SVR and M5 decision tree models performed well for the prediction of groundwater level in the Ardebil plain. However, the results obtained from the M5 decision tree model are more straightforward, more easily applied, and simpler to interpret than those from the SVR. The highest accuracy was obtained using the SVR model to predict the groundwater level from the Ghareh Hasanloo and Khalifeloo piezometers with R = 0.996 and R = 0.983, respectively.


Brain compared to heart tissue oxygen pressure during changes in arterial carbon dioxide in the dog.
Myocardial tissue oxygen pressure (PmO2 ) and left anterior descending (LAD) artery blood flow were measured in dogs anesthetized with 1.5% isoflurane, and were then compared to brain tissue oxygen pressure (PbO2 ) and middle cerebral artery (MCA) blood flow during normocapnia, hypocapnia, and hypercapnia. A craniotomy was performed and a tissue probe (Codman, Inc.) that measures PO2, PCO2, and pH was inserted into the brain cortex in the MCA region (n = 8). Separately, after a thoracotomy, a probe was inserted into the middle myocardium of the left ventricle, within the distribution of the LAD, in eight dogs. Blood flow probes were placed on the LAD or MCA. Blood flow and tissue gases were measured during normocapnia (PaCO2 = 38 mm Hg), hypocapnia (PaCO2 = 26 mm Hg), and hypercapnia (PaCO2 = 53 mm Hg). Mean arterial pressure, heart rate, arterial gases, and pH were not different between brain and heart measurements. PbO2 was 21 +/- 9 mm Hg (mean +/- SD ), 40 +/- 16 mm Hg, and 47 +/- 11 mm Hg. PmO2 was 35 +/- 12 mm Hg, 40 +/- 14 mm Hg, and 48 +/- 15 mm Hg during hypocapnia, normocapnia, and hypercapnia respectively. During hypercapnia, LAD and MCA flow increased 50% and tissue oxygenation increased 20% ( P < .05). During hypocapnia, MCA flow and PbO2 decreased 50% ( P < .05), but LAD flow and PmO2 did not significantly change. These results indicated that LAD flow and myocardial PO2 were less responsive to hypocapnia than MCA flow and PbO2.


[A two-dimensional reference map of mouse ovary proteins].
To perform a preliminary proteomic analysis of mouse ovaries and to study the protein's function in mouse ovary. The two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) were used to analyze mouse ovarian proteome. A 12.5% sodium dodecyl sulfate (SDS) reference gel was generated by immobilized pH gradient isoelectric focusing of mouse ovary proteins in a non-linear gradient (pH 3-10). And GRP78 was selected to perform with immunohistochemistry within mouse ovaries. Based on peptide mass fingerprinting, 52 proteins were identified and classified into seven functional groups: Cell/organism defense and antioxidant, cell signaling/communications proteins, cell structure/motility proteins, metabolism proteins, RNA synthesis processing, protein synthesis and processing, and unclassified proteins. The immunoreactivity of GRP78 was detected in GCs in the follicular, and with during GCs Luteinizing in the menstrual cycle, the protein expression (brown) increased continually and came to a head when ovulation happened. This work provides a first step toward the establishment of a systematic ovary protein database and stands as a valuable resource for molecular analyses of normal and pathologic conditions affecting mouse ovaries.


Resolving latent conflict: What happens when latent print examiners enter the cage?
Latent print examination traditionally follows the ACE-V process, in which latent prints are first analyzed to determine whether they are suitable for comparison, and then compared to an exemplar and evaluated for similarities and differences. Despite standard operating procedures and quality controls designed, in part, to mitigate differences between examiners, latent print processing and review are inherently subjective. The ACE-V process addresses subjectivity, and the possibility of error, in the verification stage in which a second examiner repeats the analysis, comparison, and evaluation steps in a given case. Other procedures outside the ACE-V framework, such as consultation and conflict resolution, provide further opportunity to understand how differences between latent print examiners emerge. Despite the growing body of research on latent print examination, questions have emerged about how these procedures work in practice. This study reviews case processing data for two years of casework at the Houston Forensic Science Center (HFSC). We describe these data as cases proceed through each step of the ACE-V process, with a particular focus on verification, consultation, and conflict resolution. We discuss trends in these processes regarding modal types of disagreements, modal outcomes, and roles of the examiners involved. Results reveal implications for improving the practice of latent print examination.


Taxonomy, distribution, natural history and conservation of the Russet-mantled Foliage-gleaner Syndactyla dimidiata (Pelzeln, 1859) (Aves: Furnariidae).
Russet-mantled Foliage-gleaner is an extremely poorly known species, the range of which is centered in the Brazilian Cerrado, where it inhabits riparian forests. Two subspecies are recognized, but the limits of their ranges are controversial. Furthermore, it was recently suggested that the species is one of the few in the family Furnariidae to show sexual dichromatism. In this paper we examined the plumage coloration and morphometrics of 33 study skins (85% of the available specimens). We conclude that the geographic variation and sexual dichromatism reported for S. dimidiata originated from misinterpretation of the plumage variation observed in this species, which is best considered monotypic. We also present natural history data on Russet-mantled Foliage-gleaners and suggest considering it a globally Vulnerable species.


The effectiveness of low-dose maintenance i.v. iron therapy: a dialysis facility's experience.
Over the past few decades, anemia management in patients with chronic kidney disease and end stage renal disease (ESRD) has advanced significantly. However, these improvements appear to have leveled off, with data from the ESRD Clinical Performance Measures Project showing that, over each of the past 3 years, approximately 80% of patients on hemodialysis were being managed at, or above, the minimum recommended hemoglobin (Hgb) level of 11 g/dL (Centers for Medicare & Medicaid Services, 2005). There are a number of potential reasons for this leveling off. Thus, it is important to carefully evaluate the etiology of the anemia in each patient. One area that needs to be examined involves the use of IV iron therapy. In an effort to improve anemia management, it is important for dialysis facilities to routinely examine their current IV iron protocol to determine its effectiveness in maintaining patients within the recommended target ranges for serum ferritin, transferrin saturation (TSAT), and Hgb levels. Recently the Milford Dialysis Unit took a proactive approach to improving anemia management by assessing the utility of their IV iron maintenance protocol. This review will examine the results of this analysis and provide strategies on how to improve anemia management practices in a dialysis facility.


Echocardiographic parameters and all-cause mortality: the Rotterdam Study.
Even when heart failure has not yet become clinically manifest, preclinical ventricular dysfunction may be present, and therapeutic interventions introduced at this time may reduce morbidity and mortality. However, data on the predictive value of echocardiographic characteristics in the general population remain relatively scarce. The Rotterdam Study is a population-based cohort study in men and women aged >or=55 years. Participants with prevalent heart failure, myocardial infarction and atrial fibrillation and flutter at the time of echocardiography were excluded. Structural, systolic and diastolic parameters were assessed using two-dimensional, M-mode and Doppler echocardiography. Echocardiograms were available in 4425 participants. During a mean follow-up of 3.0 years, 226 participants died. Increased left ventricular mass was an independent risk factor for all-cause mortality, particularly in men (hazard ratio per standard deviation of natural log transformed left ventricular mass, 1.20 (95% CI, 1.01-1.43)). Fractional shortening and left ventricular systolic function did not show a clear association with mortality. E/A ratio <0.75 was an independent risk factor in men (age-adjusted hazard ratio 1.82 (95% CI 1.23-2.69)). This was further reflected by diastolic function: impaired relaxation was a risk factor in men, but not in women. Structural and diastolic echocardiographic parameters are associated with all-cause mortality in an asymptomatic population. However, the evidence is still inadequate to support the usefulness of echocardiography for screening to identify asymptomatic individuals with preclinical ventricular dysfunction.


University hospitals, general hospitals, private clinics: Place-based differences in patient characteristics and outcomes of AF-A SAKURA AF Registry Substudy.
Relations between characteristics and outcomes of patients in Japan with atrial fibrillation (AF) and the type of medical facility providing their outpatient care are unclear. We compared patient characteristics and outcomes between 2 university hospitals (n=1178), 20 general hospitals (n=1308), and 41 private clinics (n=751) (follow-up: 39.3 months) in the prospective SAKURA AF Registry. Private clinic patients were significantly older than university hospital and general hospital patients (73.4±9.2 vs. 70.3±9.8 and 72.6±8.9 years; p<0.001), and these patients' CHADS2 scores were significantly lower than general hospital, but higher than university hospital patients (1.8±1.1 vs. 2.0±1.2 and 1.6±1.1; p<0.001). The Kaplan-Meier incidences of stroke/systemic embolism (SE) (1.72 vs. 1.58 vs. 0.84 events per 100 patient-years; p=0.120), a cardiovascular event (4.09 vs. 2.44 vs. 1.40; p<0.001), and death were higher (2.39 vs. 2.21 vs. 1.24; p=0.015) for university and general hospital patients than for private clinic patients; the incidences of major bleeding were equivalent (1.78 vs. 1.33 vs. 1.16; p=0.273). After multivariate adjustments, this trend persisted. Adverse clinical events at small to large hospitals appear to be higher than those at private clinics, suggesting that careful attention for preventing stroke/SE and cardiovascular events should be paid to patients at a university or general hospital.


Effect of gyrase inhibitors on some eukaryotic short-term test systems. DNase I in vitro nucleic acid synthesis and DNA repair in primary cultures of chicken embryo and rat cells.
DNase I activity was diminished by ciprofloxacin (CFL), nalidixic acid, norfloxacin, and ofloxacin in a dose-dependent manner, the MIC's (minimal significantly inhibiting concentrations) being 3.2, 2.8, 2.4, and 7.6 micrograms/ml, resp., in phase I-reaction (increase in DNA hyperchromicity) and 21, 20, 55, and 56 micrograms/ml, resp., in phase II-reaction (formation of acid-soluble products). The Line-weaver-Burk plots indicated inhibition by substrate (phase I) and uncompetitive inhibition (phase II). The decrease in scheduled DNA synthesis by CFL showed MIC's of 270, 100, 1000, and 850 micrograms/ml in chicken embryo brain (B) and liver (L) cells and in rat thymic (T) and splenic (S) cells, resp. With regard to ribonucleic acid synthesis, MIC values of 82, 82, 12.5, and 48 micrograms/ml CFL were determined, resp. Within a concentration range of 25-1600 micrograms/ml, no principal differences existed between the 4-quinolones used. In T-cells, DNA repair as induced by X-irradiation or UV-light and determined by nucleoid sedimentation was inhibited by CFL (greater than 100 micrograms/ml). The present results demonstrate biological effects of 4-quinolones on eukaryotic systems at remarkably low concentrations. In this context, the possibility of interactions with DNA catabolizing enzyme systems and synergistic effects with DNA/chromatin-damaging agents should be considered further.


[Recommendations for promoting and establishing health protection behavior with reference to AIDS].
It is proved by survey results and increasing incidence of HIV infections that general sexual behaviour did not change appreciably, although the knowledge about AIDS was distinctly improved by educational campaigns. Preventive strategies to cause changes in behaviour must be based on empirical suppositions, and must be developed in consideration of the theories. Significant models for predicting behaviour and changing attitudes are presented, and several theoretical conclusions are drawn with reference to AIDS prevention. Recommendations are made to enhance the effects of preventive strategies, and suggestions are given for a social reorientation to promote on individual behaviour change.


Doubling the clopidogrel dose in patients with reduced responsiveness to the standard dose is associated with a limited effectiveness as evaluated by impedance aggregometry.
Different methods are available for quantifying platelet function inhibition. Measuring vasodilator-stimulated phosphoprotein (VASP) phosphorylation is currently the most specific method for assessing the clopidogrel effect. The aim of our study was to compare different tests in view of a clinically applicable bedside test. Further, we examined whether doubling the clopidogrel dose to 150mg/d in clopidogrel low-responder would lead to a reduction in platelet reactivity. ADP-, ADP Hs-, and TRAP-induced platelet aggregation were measured by impedance aggregometry in 100 patients with CAD and 18 healthy controls. Moreover, platelet aggregation was assessed by flow cytometrical detection of VASP-phosphorylation and surface P-selectin in a subgroup of 34 patients and in healthy controls. Another 10 patients with CAD, identified as low-responder, were treated with a clopidogrel dose of 150mg/d. Thereafter, ADP-induced platelet aggregation was assessed by impedance aggregometry. Significant correlations were observed between ADP-induced platelet aggregation assessed by VASP-phosphorylation and by impedance aggregometry. Doubling the dose of clopidogrel to 150mg/d was associated with a reduction of ADP-induced platelet aggregation in only 60% of the patients. Impedance aggregometry is a valuable bedside test to assess platelet function inhibition. Doubling the clopidogrel dose is not effective to reduce high on-treatment platelet reactivity in almost half of these patients, pointing to the need of a more powerful platelet inhibitor.


[Percutaneous closure of interatrial septal defects: mid-term follow-up results].
We evaluated short- and mid-term results of percutaneous closure of atrial septal defects (ASD) and patent foramen ovale (PFO) using various closure devices. The study included 278 patients (128 men, 150 women; mean age 39±12 years; range 17 to 66 years) who underwent percutaneous closure of secundum ASD (n=134) or PFO (n=144). All the patients were assessed by transthoracic (TTE) and transesophageal (TEE) echocardiography before the procedure. Percutaneous closure was performed with the Amplatzer (n=180), Occlutech Figulla (n=92) or BioSTAR (n=6) devices. Closure of ASDs was performed under general anesthesia with TEE guidance, and closure of PFOs was performed under local anesthesia with TTE guidance. Follow-up controls were at 1, 6, and 12 months, and annually thereafter. The mean follow-up period was 35.1 ± 24.6 months for ASD cases, and 24.9 ± 15.5 months for PFO cases. The mean device size was 20.2 ± 5.6 mm for ASD cases and 24 ± 2.9 mm for PFO cases. The mean procedural and fluoroscopy times were 28.4 ± 6.1 min and 4.9 ± 2.1 min for ASD closure, and 18.2 ± 5.3 min and 3.6 ± 1.2 min for PFO closure, respectively. Procedural device embolization occurred in only one patient. No recurrent embolic events occurred after PFO closure, and no residual shunts were seen after ASD closure. Device thrombosis developed in two patients during the procedure and in one patient at one-year follow-up. Percutaneous closure of secundum ASDs and PFOs using the Amplatzer, Occlutech Figulla, and BioSTAR devices is an effective and safe treatment option.


Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning.
This case series documents the clinical courses of 4 patients after verapamil overdose and 1 patient after amlodipine-atenolol overdose. All subjects had hypodynamic circulatory shock (hypotension, bradycardia, and acidosis) that was not adequately responsive to conventional treatment. After initiation of insulin-dextrose infusion, the hemodynamic status of all 5 patients stabilized and all patients survived. Plasma drug concentrations are reported for all cases and verapamil levels were extremely high in 2 patients (3710 ng/mL and 3980 ng/mL). However, because patients were not treated according to a standard protocol, each patient received variable other supportive measures and inotropic agents, and the infusion rates of insulin were variable among patients. This report provides preliminary evidence toward a larger trial of insulin-dextrose to treat hypodynamic shock from calcium channel blocker overdose.


Method for determination of pulmonary gas exchange in connection with birth.
An apparatus built on the "open" system for determination of pulmonary gas exchange in the newborn infant after birth is described. At four-minute intervals diluted expired air (5-7 1/min) was collected in bags. The oxygen and carbon dioxide fraction in the bags were analysed with a Nyons Diaferometer (working on the principle of thermoconductivity). In calibration experiments using a gas-mixing technique a high degree of linearity was found, both in the determination of the fraction of oxygen and carbon dioxide (r equal to 0.9996). Reproducibility from duplicate readings was also good (for oxygen determination 0.9% and for carbon dioxide determination 0.8%). Duplicate determinations performed on infants with the same degree of motor activity resulted in an estimated error of the method of 5.8% for VO2 and 7.8% for VCO2 respectively. A metabolic chamber was used to control environmental temperature. The air temperature and wall temperature in the chamber were regulated by water from a thermostatically controlled waterbath and were kept equal within 0.5 degrees C. As the method for determination of the fraction of oxygen and carbon dioxide is not specific, other gaseous materials exhaled by the infants influence the measurements and nitrous oxide was found to interfere with the determinations, and made VO2 and VCO2 determinations in these patients impossible. Experience from more than 50 investigations on newborn infants has shown that the method is well suited to this particular type of study.


Hyperacusis: case studies and evaluation of electronic loudness suppression devices as a treatment approach.
Hyperacusis, as defined here, is a relatively rare condition in which the patient, with or without hearing loss, experiences severe loudness discomfort to everyday environmental sound levels. The case studies of 14 patients with severe hyperacusis are described; all wore passive attenuators (earplugs and/or earmuffs) in an attempt to alleviate their discomfort, frequently producing communication difficulties. These subjects were fitted binaurally with experimental electronic loudness suppression devices housed in in-the-ear casings. The devices supplied low-level amplification followed by an extreme form of amplitude compression for moderate or high-level inputs in an attempt to reduce loudness discomfort without reducing audibility. Many of the subjects were found to function with a wider dynamic range with the active devices compared with passive attenuators or the unoccluded ear, and most reported that they benefited from the devices in at least some listening situations.


Firing patterns of human flexor carpi radialis motor units during the stretch reflex.
Single motor unit and gross surface electromyographic responses to torque motor-produced wrist extensions were studied in human flexor carpi radialis muscle. Surface EMG typically showed two "periods" of reflex activity, at a short and long latency following stretch, but both periods occurring before a subject's voluntary reaction to the stretch. The amplitude of EMG activity in both reflex periods increased monotonically with an increase in the torque load. The amplitude of the short-latency reflex response was very dependent on the motoneuron pool excitability, or preload. The amplitude of the long-latency reflex response also varied with the preload, but could, in addition, be modulated by the subject's preparatory set for a voluntary response to the imposed displacement. When a single motor unit that was not tonically active began to fire during the stretch reflex, it did so primarily during the long-latency period. When caused to fire repetitively by voluntary facilitation of the motoneuron pool, that same unit now showed activity during both periods of the stretch reflex. Further increases in either motoneuron pool facilitation or in perturbation strength resulted in a monotonic increase in response probability of a single motor unit during the short-latency period. However, the response probability of a single unit during the long-latency reflex period did not always vary in a monotonic way with increases in either torque load or motoneuron pool facilitation. For an additional series of experiments, the subject was instructed on how to respond voluntarily to the upcoming wrist perturbation. The three instructions to the subject had no effect on the response probability of a single motor unit during either the background or short-latency periods of the stretch reflex. However, prior instruction clearly affected a unit's response probability during the long-latency reflex period. Changes in the firing rate of motor units, and in the recruitment or derecruitment of nontonic units, contributed to this modulation of reflex activity during the long-latency period.


[Quantitative characteristics of polarization images].
Paper shows that quantitative data on the anisotropic structures in the form of three-dimensional images having a high spatial resolution could be practically obtained and presents the results of examining a number of anisotropic objects using the experimental model of a computerized polarizing microscope.


[Ecological issues and loss risk of cold-resistant rubber germplasm resource in Xishuangbanna].
Based on the field investigation data and related literatures, this paper analyzed the ecological issues in the breeding and utilization of highly cold-resistant and high-yielding rubber germplasm in Xishuangbanna, and the loss risk of this germplasm. The rubber farmers in Xishuangbanna had built a cycle pattern of establishing rubber nursery and managing rubber plantations to develop the local rubber industry, but the unlimited utilization of this germplasm made the rubber plantations expand to the highland with an elevation of 1300 m, resulting in the ecological issues such as the destruction of natural forests and species, decline of soil fertility, regional drought, rubber diseases and insect pests, and human-elephant conflicts. This germplsm and its intellectual property were under transnational loss without any control, making even more potential ecological and economic risks. Great attentions should be paid by the related organizations to take effective measures to conserve this germplsm resource to reduce its potential risks.


Human diseases with defects in oxidative phosphorylation. 1. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies.
The amount of oxidative phosphorylation enzymes in mitochondrial encephalomyopathy patients has been studied by two-dimensional electrophoresis (blue native PAGE/Tricine-SDS-PAGE). Only 20 mg muscle was required to identify and analyse complexes I, III, IV, and V after Coomassie staining. In most cases reduced amounts of the involved complex(es) correlated well with decreased enzyme activities. The reliability of the method was reflected by the constant mutual ratio of the complexes found in all controls. Deviations from normal ratios were found to be more sensitive indicators for a defect than the absolute quantities, which varied considerably within the control group both in the enzymic and in the electrophoretic analysis. The effect of the mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes on the amount of oxidative phosphorylation complexes was demonstrated for the first time directly on the protein level. In patients without known DNA mutations, specific defects of single complexes were identified. The new technique is a sensitive method for the identification of oxidative phosphorylation defects, complementary to enzymic measurements.


Expectancy, redefinition and reported pain.
Three groups of subjects were administered a redefinition strategy which asked them to focus on sensations during noxious stimulation. Those in one group were informed that the strategy would reduce pain (positive expectancy), those in a second were informed that it would augment pain (negative expectancy), and those in a third were given no information on expectancy. Subjects in a fourth group received neither redefinition nor instructions on expectancy. The four groups did not differ either in expectancy of pain reduction or in reduction of reported pain. Subjects in all groups expected more pain than they reported, and expectations for pain reduction showed only a small correlation with degree of reported pain reduction. In all groups, men reported less pain than women.


The association of preprocedural anxiety and the success of procedural sedation in children.
To investigate the association between a child's preprocedural state anxiety and the success of sedation. A consecutive sample of children aged 2 through 17 years requiring sedation for a procedure was enrolled. Pain, preprocedural anxiety (range, 0-9), and success of sedation (10=most successful) were measured. Fifty-nine patients were enrolled. The median age was 7 years. The median anxiety score was 1.0 (interquartile ratio, 0-3). Pain and anxiety were weakly correlated (r=.21, P>.10). The mean sedation score was 7.8 (+/-2.2). Preprocedural anxiety and successful sedation were inversely correlated (r=-0.31, P=.002). Sedation was successful in 81% of children with anxiety scores below the median and 52% with anxiety scores above the median (P=.02). Children with low anxiety were 3.8 times more likely to be successfully sedated (95% confidence interval, 1.19-12.14). Our data suggest that preprocedural state anxiety is associated with the success of sedation in children.


Can we rely on PET in the follow-up of advanced seminoma patients?
The management of residuals after completion of chemotherapy in advanced seminoma is controversial. It has been proposed that fluorodeoxyglucose-positron emission tomography (FDG-PET) can be used as a follow-up. In this study we investigated FDG-PET as a follow-up tool in advanced seminoma patients treated previously with chemotherapy or radiotherapy. Thirty-seven patients assigned to an advanced seminoma group based on CT and/or FDG-PET/CT and then treated with chemotherapy were included in the study. All these patients underwent FDG-PET/CT examination as a part of the follow-up scheme. Patients underwent retroperitoneal lymph node dissection (RPLND), radiotherapy, or were followed clinically by CT and/or PET/CT every 6 months. In 8 cases FDG-PET was positive: 5 of them underwent RPLND and 3 radiotherapy. Two patients with negative FDG-PET but positive CT also underwent RPLND. The remaining patients with negative FDG-PET results were followed up. FDG-PET/CT was false positive in one case >3 cm and one <3 cm, in 6 cases >3 cm it was true negative. While FDG-PET can find a viable tumor, there also is an important question of false positive results. It was clinically proven that a negative FDG-PET was correlated with stable disease, but we were unable to examine specimens in these cases.


Experimental determination of the reference plane of shaped diffusers by solar ultraviolet measurements.
The optical reference plane of a J1002 shaped dome diffuser from CMS-Schreder was determined using direct normal spectral solar UV irradiance measurements relative to a flat Teflon diffuser. The spectroradiometers were calibrated relative to the same irradiance standard. The optical reference plane of the shaped J1002 diffuser is 5.3 mm behind the top of the dome with an uncertainty of 1.0 mm. Solar UV irradiance measurements based on a lamp calibration using the top of the dome as the reference will overestimate the global solar irradiance by 2.1% for the usual calibration distance of 500 mm.


Pregnancy outcome in severe placental abruption.
To determine the relationship between decision to delivery interval and perinatal outcome in severe placental abruption. A case-control study. Large inner city teaching hospital. Retrospective case note review of pregnancies terminated following severe placental aburption and fetal bradycardia. One year paediatric follow up by case note review or postal questionnaire. The differences in outcome (death or cerebral palsy) were examined using non-parametric and univariate analysis for the following time periods--times from onset of symptoms to delivery, onset of symptoms to admission, admission to delivery, onset bradycardia to delivery and decision to delivery interval. Prenatal death or survival with cerebral palsy. Thirty-three women with singleton pregnancies over 28 weeks of gestation, admitted with clinically overt placental abruption, where delivery was effected for fetal bradycardia. Eleven of the pregnancies had a poor outcome (cases), eight infants died and three surviving infants have cerebral palsy. Twenty-two pregnancies had a good outcome (controls): survival with no developmental delay. No statistically significant relationship was found between maternal age, parity, gestation, or birthweight and a poor outcome. A statistically significant relationship between time from decision to delivery was identified (P = 0.02, Mann-Whitney U test). The results of a univariate logistic regression for this variable suggest that the odds ratio of a poor outcome for delivery at 20 minutes compared with 30 minutes is 0.44 (95% CI 0.22-0.86). Fifty-five percent of infants were delivered within 20 minutes of the decision to deliver. Serious maternal morbidity was rare. In this small study of severe placental abruption complicated by fetal bradycardia, a decision to delivery interval of 20 minutes or less was associated with substantially reduced neonatal morbidity and mortality.


Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats.
Plasma apolipoprotein (apo) E, a sialoprotein, plays an important role in reverse cholesterol transport. Previously, we showed that chronic alcohol consumption impairs glycosylation of apo E in rat liver. Peritoneal macrophages are another significant apo E synthesis site. The main purpose of this study was to determine the effects of chronic alcohol feeding of rats on the synthesis, sialylation, and sialic acid content of macrophage apo E and its ability to bind to the HDL(3) molecule in vitro. Rats were fed an alcoholic diet or an isoenergetic control diet for 8 wk, after which peritoneal macrophages isolated from them were cultured and analyzed for apo E metabolism. Macrophages from alcohol-fed rats accumulated 33.3% more (P < 0.05) cholesterol than did those from control rats when incubated with acetylated LDL. These macrophages showed a 51-57% lower relative sialylation rate of apo E (P < 0.001) but no significant difference in relative protein synthetic rate. The sialic acid content of the intracellular and secreted forms of apo E was reduced by 41.8% (P < 0.001) and 50.3% (P < 0.001), respectively, with chronic alcohol treatment. Secretion of newly synthesized apo E was impaired by 53.7% (P < 0.001) and 26. 1% (P < 0.001) in the absence and presence of HDL in the medium, respectively. Macrophages of alcohol-treated rats secreted apo E with 47.6-67.2% lower (P < 0.001) HDL(3) binding ability; binding ability was restored completely by resialylation of the desialylated apo E. In rats, an alcohol-mediated decrease in sialylation rate resulting in loss of sialic acid residues in apo E impairs the ability of apo E to bind to HDL and consequently in defective reverse cholesterol transport.


Effectiveness of the parent-mediated intervention for children with autism spectrum disorder in south Asia in India and Pakistan (PASS): a randomised controlled trial.
Autism spectrum disorder affects more than 5 million children in south Asia. Although early interventions have been used for the treatment of children in high-income countries, no substantive trials have been done of the interventions adapted for use in low-income and middle-income countries (LMICs). We therefore assessed the feasibility and acceptability of the parent-mediated intervention for autism spectrum disorder in south Asia (PASS) in India and Pakistan. A single-blind randomised trial of the comparison of 12 sessions of PASS (plus treatment as usual) with treatment as usual alone delivered by non-specialist health workers was done at two centres in Goa, India, and Rawalpindi, Pakistan. Children aged 2-9 years with autism spectrum disorder were randomly assigned (1:1) by use of probabilistic minimisation, controlling for treatment centre (Goa or Rawalpindi), age (<6 years or ≥6 years), and functional impairment (Vineland Adaptive Behaviour Scale Composite score <65 or ≥65). The primary outcome was quality of parent-child interaction on the Dyadic Communication Measure for Autism at 8 months. Analysis was by intention to treat. The study is registered with ISRCTN, number ISRCTN79675498. From Jan 1 to July 30, 2013, 65 children were randomly allocated, 32 to the PASS group (15 in Goa and 17 in Rawalpindi) and 33 to the treatment-as-usual group (15 in Goa and 18 in Rawalpindi). 26 (81%) of 32 participants completed the intervention. After adjustment for minimisation factors and baseline outcome, the primary outcome showed a treatment effect in favour of PASS in parental synchrony (adjusted mean difference 0·25 [95% CI 0·14 to 0·36]; effect size 1·61 [95% CI 0·90 to 2·32]) and initiation of communication by the child with the parent (0·15 [0·04 to 0·26]; effect size 0·99 [0·29 to 1·68]), but time in mutual shared attention was reduced (-0·16 [-0·26 to -0·05]; effect size -0·70 [-1·16 to -0·23]). Our results show the feasibility of adapting and task-shifting an intervention used in a high-income context to LMICs. The findings also replicate the positive primary outcome treatment effects of a parent-mediated communication-focused intervention in the original UK Preschool Autism Communication Trial, with one negative effect not reported previously. Autism Speaks, USA.


Cumulative lifetime migraine incidence in women and men.
The aim was to estimate lifetime sex and age-specific incidence of migraine. Data are from the American Migraine Prevalence and Prevention study, a mailed survey sent to 120,000 US households. Age-specific incidence was estimated using self-reported data relevant to identification of migraine cases, age of onset of migraine and age at interview. Migraine incidence peaked between the ages of 20 and 24 years in women (18.2/1000 person-years) and the ages of 15 and 19 years in men (6.2/1000 person-years). Cumulative incidence was 43% in women and 18% in men. Median age of onset was 25 years among women and 24 years among men. Onset in 50% of cases occurred before age 25 and in 75% before age 35 years. Four of every 10 women and two of every 10 men will contract migraine in their lifetime, most before age 35 years. The incidence estimates from this analysis are consistent with those reported in previous longitudinal studies.


Phosphorylation of Sendai virus phosphoprotein by cellular protein kinase C zeta.
The phosphoproteins (P) of nonsegmented negative strand RNA viruses are viral RNA polymerase subunits involved in both transcription and replication during the virus life cycle. Phosphorylation of P proteins in several negative strand RNA viruses by specific cellular kinases was found to be required for P protein function. In the present study, using bacterially expressed unphosphorylated P protein of Sendai virus, a mouse parainfluenza virus, we have shown that the major cellular kinase that phosphorylates P protein in vitro is biochemically and immunologically indistinguishable from protein kinase C (PKC) zeta isoform. PKC zeta was packaged into the Sendai virion and remained associated with purified viral ribonucleoprotein, where it phosphorylated both the P and the nucleocapsid protein in vitro. When PKC zeta-specific inhibitory pseudosubstrate peptide was introduced into LLC-MK2 cells prior to Sendai virus infection, production of progeny virus was dramatically attenuated, and kinetic analysis revealed that primary transcription was repressed. These data indicate that phosphorylation of the Sendai virus P protein by PKC zeta plays a critical role in the virus life cycle.


Significance of slow upsloping ST-segment depression on exercise stress testing.
The supplementary value of varying degrees of upsloping ST-segment depression observed during treadmill exercise testing to the accuracy of the exercise ST-segment response for detection of ischemia was determined by employing a reversible thallium-201 (201Tl) defect as the criteria for ischemia. A group of 199 consecutive patients (168 men) with > or = 1 reversible 201Tl defects on quantitative planar perfusion imaging, and a normal group of 366 patients with normal 201Tl scans who achieved > or = 85% of age-predicted maximum heart rate were studied. Upsloping ST-segment depression was subcategorized for > or = 1.0, > or = 1.5, and > or = 2.0 mm of sustained ST-segment depression below baseline at 0.08 seconds after the J-point. If only > or = 1.0 mm of horizontal or downsloping ST-segment depression was designated as abnormal and all upsloping responses as normal, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the exercise electrocardiogram were 49% (98 of 199), 84% (281 of 336), 64% (98 of 153), 74% (281 of 382), and 71% (379 of 535), respectively. If in addition to > 1.0 mm of horizontal or downsloping ST-segment depression, > or = 2.0 mm of upsloping ST-segment depression is considered abnormal, these values were 52% (104 of 199), 81% (272 of 336), 62% (104 of 168), 74% (272 of 367), and 70% (376 of 535), respectively. If > or = 1.5 mm of upsloping ST-segment depression is considered an abnormal response, these values were 59% (117 of 199), 74% (248 of 336), 57% (117 of 205), 75% (248 of 330), and 68% (365 of 535), respectively. Finally, if > or = 1.0 mm of upsloping ST-segment depression is considered abnormal, these values were 71% (142 of 199), 56% (187 of 336), 49% (142 of 291), 77% (187 of 244), and 61% (329 of 535), respectively. Thus, if upsloping ST-segment depression is added to the criteria for a positive exercise test result, sensitivity for detection of ischemia is increased but at the expense of a fall in specificity and a significant decrease in the positive predictive value of the test.


Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy.
Establishing factor IX inhibition in patients with acute coronary syndrome/non-ST-elevation myocardial infarction (ACS/NSTEMI), a setting characterized by increased factor IX activity, is critical to investigate the REG1 system in this target population. The REG1 system (Regado Biosciences, Basking Ridge, NJ) consists of pegnivacogin (RB006), an RNA aptamer that directly inhibits factor IXa, and anivamersen (RB007), its complementary control agent. RADAR is a Phase 2b study investigating the use of pegnivacogin in patients (n = 800) with ACS undergoing planned early cardiac catheterization. To validate dose selection and stability of anticoagulation throughout the time of cardiac catheterization at an early stage of the clinical trial, 33 patients, 22 of whom had not received recent prior heparin, underwent thorough pharmacokinetic and pharmacodynamic assessment. Fold prolongation of activated partial thromboplastin time (aPTT) was used to impute factor IX inhibition. Pegnivacogin 1 mg/kg rapidly achieved a high pegnivacogin plasma concentration (26.1 ± 4.6 µg/mL), prolonged the aPTT (mean aPTT 93.0 ± 9.5 s), and approached near complete factor IX inhibition (mean fold increase from baseline 2.9 ± 0.3). These levels remained stable from the time of drug administration through completion of the catheterization. Pegnivacogin administered at a weight-adjusted dose of 1 mg/kg consistently achieves a high level of factor IX activity inhibition among patients with ACS and provides stable anticoagulation during cardiac catheterization. These findings support the dose of pegnivacogin selected for the RADAR study.


Breast cancer cell proliferation is inhibited by BAD: regulation of cyclin D1.
Recent investigations suggest that functions of the proapoptotic BCL2 family members, including BAD, are not limited to regulation of apoptosis. Here we demonstrate that BAD inhibits G(1) to S phase transition in MCF7 breast cancer cells independent of apoptosis. BAD overexpression inhibited G(1) transit and cell growth as well as cyclin D1 expression. Inhibition of cyclin D1 expression was mediated through inhibition of transcription activated by AP1. Chromatin immunoprecipitation assays indicated that BAD is localized at the 12-O-tetradecanoylphorbol-13-acetate-response element (TRE) and cAMP-response element (CRE) in the cyclin D1 promoter. This was shown to reflect direct binding interactions of BAD with c-Jun, and this interaction inhibited the activity of AP1 complexes at TRE. BAD did not interact with phosphorylated forms of c-Jun. Our data suggest that inhibitory TRE/CRE-c-Jun-BAD complexes are present at the cyclin D1 promoter in quiescent cells. Estrogen stimulation displaced BAD from TRE/CRE elements in MCF7 cells, whereas BAD overexpression inhibited estrogen-induced cyclin D1 synthesis and cell proliferation. Inhibition of endogenous BAD in MCF7 cells markedly increased the proliferative fraction and DNA synthesis, activated Cdks, and increased cyclin D1 protein levels. This action of BAD required serine residues Ser(75) and Ser(99). Both phosphorylated and unphosphorylated forms of BAD localized to the nuclei of human breast epithelial cells. Thus, we demonstrate a novel role for BAD in cell cycle regulation dependent upon its phosphorylation state and independent of the BAD/BCL2 interaction and apoptosis.


A quick glance at selected topics in this issue.
"A quick glance at selected topics in this issue" aims to highlight contents of the Journal and provide a quick review to the readers.


Cell viability, adhesion and function of RAW 264.7 macrophages on fluorinated xerogel-derived nitric oxide permeable membrane for the application of cellular sensing.
Organically modified xerogels have an advantage over gas sensing applications due to their open, rigid structure and hydrophobicity. Here we evaluated the biocompatibility of xerogel-derived nitric oxide (NO) permeable membranes modified with fluorinated functional groups for application in cellular sensing by growing RAW 264.7 macrophages on them. We examined the cell viability, adhesion and growth of RAW 264.7 macrophages on NO permselective membrane and other cell-adhesive matrices, poly L-lysine and collagen. The surface roughness of each membrane was obtained from topographic atomic force microscopy (AFM) images. In addition, we measured the level of NO release of RAW 264.7 macrophages by lipopolysaccharide (LPS) stimulation using a Griess assay to confirm the function of cells. The fluorinated xerogel-derived membrane had a very smooth surface with rms roughness 2.1 Å and did not show cytotoxic effects in RAW 264.7 macrophages. As a result, the morphology and function of adhering RAW 264.7 macrophage showed no differences from those of other cell-adhesive membranes. Finally, we successfully detected NO release in RAW 264.7 macrophages stimulated by LPS, using a planar-type xerogel-derived NO sensor. Therefore, we suggest that fluorinated xerogel-derived membrane could be used as both a NO permeable and cell-adhesive membrane for cellular sensing applications.


Tracheobronchial injuries in chest trauma: a 17-year experience.
to discuss the clinical and therapeutic aspects of tracheobronchial lesions in victims of thoracic trauma. we analyzed the medical records of patients with tracheobronchial lesions treated at the São Paulo Holy Home from April 1991 to June 2008. We established patients' severity through physiological (RTS) and anatomical trauma indices (ISS, PTTI). We used TRISS (Trauma Revised Injury Severity Score) to evaluate the probability of survival. nine patients had tracheobronchial lesions, all males, aged between 17 and 38 years. The mean values of the trauma indices were: RTS - 6.8; ISS - 38; PTTI - 20.0; and TRISS - 0.78. Regarding the clinical picture, six patients displayed only emphysema of the thoracic wall or the mediastinum and three presented with hemodynamic or respiratory instability. The time interval from patient admission to diagnosis ranged from one hour to three days. Cervicotomy was performed in two patients and thoracotomy, in seven (77.7%), being bilateral in one case. Length of hospitalization ranged from nine to 60 days, mean of 21. Complications appeared in four patients (44%) and mortality was nil. tracheobronchial tree trauma is rare, it can evolve with few symptoms, which makes immediate diagnosis difficult, and presents a high rate of complications, although with low mortality.


Essential oil of trees of the genus Ocotea (Lauraceae) in Costa Rica. I. Ocotea brenesii.
The chemical composition of the essential oils from leaves and wood of Ocotea brenesii Standl. growing wild in Costa Rica was determined by capillary GC/FID and GC/MS. From the leaves, 64 compounds were identified, corresponding to 85.9% of the oil, and from the wood 57 compounds were identified corresponding to 69.0% of the oil. The major constituents identified in the leaf oil were alpha-copaene (21. 1%), 8-cadinene (9.2%), spathulenol (7.3%), globulol (5.6%) and beta-caryophyllene (5.2%). The major constituents of the wood oil were alpha-copaene (6.6%), caryophyllene oxide (6.3%). beta-caryophyllene (6.1%) and humulene epoxide (4.6%).


Developmental toxicity study of lersivirine in mice.
Lersivirine is a second-generation nonnucleoside reverse transcriptase inhibitor undergoing clinical development for the treatment of HIV-1. An embryo-fetal developmental toxicity study was performed to evaluate the maternal and developmental toxicity of lersivirine in pregnant mice. Mated Crl:CD1(ICR) mice were administered 0, 150, 350, and 500 mg/kg lersivirine once daily by oral gavage on gestation days 6 to 17, followed by cesarean section on gestation day 18. The first 2 days of dosing for the high-dose group were done at 250 mg/kg to allow induction of hepatic metabolizing enzymes, after which the dose was increased to 500 mg/kg/day. This dosing paradigm allowed for maintenance of exposure in the high-dose group despite the considerable autoinduction that occurs in rodents following lersivirine treatment. Lersivirine did not cause an increase in external, visceral, or skeletal malformations. Intrauterine growth retardation, demonstrated by reduced fetal body weights and increased variations associated with delayed skeletal ossification, was noted at 350 and 500 mg/kg/day. The results of these studies indicate that lersivirine is not teratogenic in mice.


[The function of nitric oxide in the necrosis of avulsed skin flap in domestic pig].
To investigate the function of nitric oxide (NO) and nitric oxide synthetase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), the skin avulsion model was made in the lower extremity of pig. The methods of measurement of size of the survived flap, weighing, immunocytochemistry and hybridization in situ were employed, so that the survival surface area of flaps, tissue wet/dry weight ratio, NO content in the serum, gene expression of NO and NOS content in the flap tissue were determined, respectively. The results showed that the early gene expression of NOS was increased as well as the NO content and tissue wet/dry weight ratio (P < 0.01). After L-NAME was applied introvenously, the NO content and tissue wet/dry weight ratio were decreased (P < 0.01), and the survival surface area of flaps was enlarged (P < 0.01). It could be concluded that the NO might play a role in the development of the pathological changes as early congestion, edema and secondary necrosis in the avulsed skin flaps. The early application of L-NAME could do some good to the avulsed skin flap and protect it from further necrosis owing to the presence of NO.


Role of P-glycoprotein and the intestine in the excretion of DPC 333 [(2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide] in rodents.
The role of the intestine in the elimination of (2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide (DPC 333), a potent inhibitor of tissue necrosis factor alpha-converting enzyme, was investigated in mice and rats in vivo and in vitro. In Madine-Darby canine kidney cells stably transfected with P-glycoprotein (P-gp) and DPC 333, the transport from B-->A reservoirs exceeded the transport from A-->B by approximately 7-fold. In Caco-2 monolayers and isolated rat ileal mucosa, DPC 333 was transported from basolateral to apical reservoirs in a concentration-dependent, saturable manner, and transport was blocked by N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), confirming the contribution of P-gp/breast cancer resistance protein in B-->A efflux of DPC 333. In quantitative whole body autoradiography studies with [(14)C]DPC 333 in mice and rats, radioactivity was distributed throughout the small intestine in both species. In GF120918-pretreated bile duct-cannulated rats, radioactivity in feces was reduced 60%. Using the in situ perfused rat intestine model, approximately 20% of an i.v. dose of [(14)C]DPC 333 was measured in the intestinal lumen within 3 h postdose, 12% as parent. Kinetic analysis of data suggested that excreted DPC 333 may be further metabolized in the gut. Intestinal clearance was 0.2 to 0.35 l/h/kg. The above data suggest that in the rodent the intestine serves as an organ of DPC 333 excretion, mediated in part by the transporter P-gp.


Cortical Aquaporin-4 in relation to brain oedema and neurological function of cortical cryo-injured mice.
To estimate the spatial and temporal expression of Aquaporin-4 (AQP-4) in a murine model of automated cerebral cryoinjury and correlate AQP-4 expression with development of brain oedema and neurological function. AQP-4 levels were determined quantitatively by Western blots at site of injury and at sites adjacent to and distant from injury in brains of cryoinjured (experimental) (n=18), sham injured (n=18) & normal mice at 24, 48, 72h post injury. AQP-4 expression was correlated with percentage water content of brain, Neurological Severity Score (NSS) and rotarod scores. We found a 1.4-fold increase in expression of AQP-4 at the site of injury and at sites distant from injury at 24h when compared to normal mice (p=0.05). The increase in expression of AQP-4 24h post injury was significantly higher in experimental group at the site of injury and at the site adjacent to the injury in the ipsilateral hemisphere when compared to the sham injured mice (p=0.05). At 24h post injury the median NSS score in the experimental group was 9 (interquartile range 7.25-10) and that in the sham group was 0.5 (interquartile range 0.0-1.0) (p<0.001). At 48 and 72h, AQP-4 expression remained elevated in the experimental group when compared to normal brain, but the levels were not significantly different from that in sham group. AQP-4 expression was significantly elevated in the ipsilateral hemisphere in the first 24h following cerebral cortical injury in mice and this could be correlated with worsening of neurological function. Over the next 48h, there was a trend towards decrease in AQP-4 expression that was associated with partial recovery of neurological function.


Effects of oral glucose on systemic glucose metabolism during hyperinsulinemic hypoglycemia in normal man.
The widespread use of oral glucose in the treatment of hypoglycemia is mainly empirically based, and little is known about the time lag and subsequent magnitude of effects following its administration. To define the systemic impact and time course of effects following oral glucose during hypoglycemia, we investigated 7 healthy young men twice. On both occasions, a 6-hour hyperinsulinemic (1.5 mU/kg/min)-hypoglycemic clamp was performed to ensure similar plasma glucose profiles during a stepwise decrease toward a nadir less than 50 mg/100 mL after 3 hours. On the first occasion, subjects ingested 40 g glucose and 4 g 3-ortho-methylglucose ([3-OMG] to trace glucose absorption) dissolved in 400 mL tap water after 3.5 hours. The second examination was identical except for the omission of 40 g oral glucose, and glucose levels were clamped at hypoglycemic concentrations similar to those recorded on the first examination. Plasma glucose curves were superimposable, and all participants reached a nadir less than 50 mg/100 mL. Similar increases in growth hormone (GH) and glucagon were observed in both situations. The glucose infusion rates (GIRs) were lower after oral glucose, with the difference starting after 5 to 10 minutes, being statistically significant after 20 minutes, and reaching a maximum of 8.5 +/- 1.6 mg/kg/min after 40 minutes. Circulating 3-OMG increased after 20 minutes. In both situations, infusion of insulin resulted in insulin levels of approximately 150 microU/mL and a suppression of C-peptide levels from 2.0 to 1.1 nmol/L (P < .01). After glucose ingestion, both serum C-peptide and glucagon-like peptide-1 (GLP-1) increased (C-peptide from 1.1 +/- 0.05 to 1.4 +/- 0.05 nmol/L and GLP-1 from 3.2 +/- 0.8 to 18.1 +/- 3.3 pmol/L), in contrast to the situation without oral glucose (P < .05). Isotopically determined glucose turnover was similar. In conclusion, our data suggest that oral glucose affects systemic glucose metabolism rapidly after 5 to 10 minutes. Quantitatively, the immediate impact is relatively small, with the gross impact observed after approximately 40 minutes. Future studies aiming to identify therapeutic oral agents with prompt effect seem warranted.


Effect of novel mixed ETA/ETB antagonists on responses to ET-1 in human small muscular pulmonary arteries.
Selective ETA and ETB receptor antagonists do not fully inhibit responses to ET-1 in human small pulmonary arteries. Here, we have compared the influence of the novel mixed ETA/ETB antagonists SB/217242, SB/234551 and SB/209670 on ET-1-mediated vasoconstriction in these vessels. ET-1 was a potent vasoconstrictor (pEC50: 8.14+/-0.05, n=5) and the concentration-response curve to ET-1 was biphasic in nature. All three mixed antagonists (1 microM) inhibited the responses to ET-1, abolishing the biphasic form of the concentration response curve. The order of potency was SB 209670>SB 234551>/=SB 217242 with estimated pKb values of 8.0+/-0.20, 6.8+/-0.17 and 6. 6+/-0.11 respectively (n=3-5).


"Speak Up, We Can't Hear You".
The author supports the lead authors' call for physicians to be open about their support for legalized assisted death. Citing evidence from Canada and internationally, the author demonstrates that support for euthanasia is growing in the medical community, and that many physicians would like to see legislative changes to support this trend. The commentary concludes with a call for physicians to educate themselves so that they can advocate more effectively on behalf of their patients.


Effects of biochar-BDE-47 interactions on BDE-47 bioaccessibility and biodegradation by Pseudomonas putida TZ-1.
With biochar amendments widely accepted as efficient POPs contamination remediation methods, the post-remediation risk assessment and effectiveness evaluation were urgently needed. So in the study, the effects of biochar -2,2',4,4'-tetrabromodiphenyl ether (BDE-47) interactions on the bioaccessibility and biodegradation of BDE-47 were systematically examined. Biodegradation was monitored over 7 day incubation time with strain Pseudomonas putida TZ-1 and it was revealed that the presence of three model biochars dramatically decreased the biodegradation rate by 87.50-92.19%. The desorption rate gradually decreased to eventually make it a rate-limiting process for BDE-47 biodegradation. To further explore the impact of biochar-BDE-47 sorption on its bioaccessibility, chemical extraction and biosurfactant facilitated desorption experiments were conducted. Both results suggested that almost all the molecules sorbed onto non-porous biochars could be completely desorbed, whereas BDE-47 molecules sequestered within deep micropores were more persistent on the solid phase, and resulted in lower bioaccessibility.


Outcome of compartment resection of locally advanced oral cancers extending to infratemporal fossa: a tertiary rural hospital experience.
Locally advanced oral cancers extending to infratemporal fossa (ITF) are a challenge to head and neck surgeons. These tumors are classified as T4b whenever the masticator space (MS), pterygoid muscles (PM), and pterygoid plates (PP) are involved according to AJCC classification. Until recently, these tumors were considered inoperable and treated only with palliative intent. However, a few studies in the last decade showed that many of these tumors could be resected with a reasonably favorable prognosis by compartment resection of ITF, particularly when the tumor was below sigmoid notch of mandible. A few studies attempted to downstage these tumors by neo-adjuvant chemotherapy before attempting resection. Oral Squamous cell carcinoma has a high prevalence in South India. Majority of these patients are females addicted to tobacco quid chewing and present with locally advanced disease. In this retrospective analysis, we evaluated the outcome of treatment of oral squamous cell carcinoma extending to ITF and staged T4b in 52 patients. All patients underwent Composite resection including compartment resection of ITF followed by adjuvant treatment. 20 patients had received neo-adjuvant chemotherapy. Pectoralis major myocutaneous flap was the mainstay of reconstruction. After mean follow-up of 2 years, 31 patients are alive and disease free. 14 patients had local recurrence in ITF and 2 patients had recurred in cervical nodes. 8 patients died due to disease and 6 are on palliative care. Neo-adjuvant chemotherapy did not benefit the outcome. Close margins of resection, extra nodal spread from lymph nodes and supra notch and involvement of posterior part of ITF were factors which predisposed to recurrence.


Single bilobed flap for use in head and neck reconstruction.
A new bilobed cutaneous and myocutaneous flap providing ipsilateral reconstruction possibilities in the head and neck is described. The flap incorporates the pectoralis major myocutaneous flap and the medially based deltopectoral flap in a single bilobed flap. Both flaps come from the same side to provide bulk and cutaneous coverage in a single flap.


[Retinal pigment epithelial detachment].
The vast majority of cases of AMD involve widespread disease with visible neovascularization, "occult" neovascularization, and serous as well as hemorrhagic detachments of the RPE. Accurate interpretation of the clinical and fluorescein angiographic findings in PEDs is difficult. The most noteworthy problem is the recognition of the presence and extent of associated neovascularization. Definitive guidelines for laser photocoagulation treatment of these PEDs have not yet been established. Large-scale, sophisticated clinical trials are needed to assess the efficacy and safety of laser treatment for this important manifestation of exudative AMD. Until these investigations are completed, certain cases of PEDs may be selected for laser treatment by one of three treatment techniques. A grid pattern photocoagulation to a serous PED may be carried out when there is no demonstrable or suspected underlying SRN and there is persistence and progression of the detachment with associated visual decline. Total photocoagulation of the PED which is suspected of having neovascularization can also be carried out if the fovea can be spared. Finally, photocoagulation of extrafoveal neovascularization beneath or at the margin of a PED can be performed in an attempt to obliterate the neovascularization, resolve the exudative manifestations, and stabilize or improve the vision. Only experienced retinal specialists who are well trained in the recognition of the complex clinical and fluorescein angiographic features of PEDs should attempt to treat these unusual and complicated cases.


Experiences and attitudes about faith healing among family physicians.
Recent media attention has focused on patients who use faith healers to care for their medical problems. Many people who use faith healers also consult physicians. This study was done to learn more about how often physicians see patients who are involved in faith healing, and to learn more about physicians' attitudes about, and experiences with, faith healing. A 1-page questionnaire was mailed to 1025 family physicians in seven states; 594 participated, for a response rate of 59%. Approximately one half (52%) of the physicians were aware of at least one patient in their practice who had had a faith-healing experience. Most physicians came in contact with such patients no more frequently than once a year. Fifty-five percent agreed and 20% disagreed that reliance on faith healers often leads to serious medical problems. However, 44% thought that physicians and faith healers can work together to cure some patients, and 23% believed that faith healers divinely heal some people whom physicians cannot help. These results suggest that family physicians are infrequently aware of faith-healing beliefs and experiences among their patients. Family physicians were divided in their views about faith healing, with a majority expressing skepticism about faith healing and a sizeable minority favorable toward it.


Spatial imbalance and changes in supply and demand of ecosystem services in China.
Human activities and regional land development have caused intense interference to ecosystems. With rapid development of economy and urgent needs of life quality improvements in China, sustainable ecosystem management is crucial for national ecological civilization construction. However, few studies have focused on supply-demand patterns of ecosystem services on a national scale in China. The aim of this study was to analyze the spatial-temporal patterns and changes in the supply-demand of ecosystem services and to explore their interactive relationship in the context of economic development and urbanization drivers. The ecosystem services provision index (ESPI) and land development index (LDI) were proposed to indicate the supply and demand for ecosystem services. The results indicated that the Low supply-High demand (L-H) pattern accounted for 3.27% of the total land area in China and was mainly concentrated in developed regions and some capital cities, where 28.95% of the total population and 51.93% of the country's GDP was generated in 2015. The spatial imbalance in the supply-demand of ecosystem services was obvious. From 2000 to 2015, the imbalance was shrinking, and regions with negative changes in supply-demand patterns were declining. During 2000-2008, there was an obvious transformation from Low supply-Low demand (L-L) to High supply-Low demand (H-L), which accounted for 12.44% of the total land area due to Grain for Green and other ecological protection policies. The proportion of ecological land to total land area, vegetation cover and elevation were significantly correlated with the supply of ecosystem services. In the meantime, ESPI was negatively correlated with LDI in most regions in China. There were also regional differences in their relationships. The rapid economic growth and the intensive land development resulted in a more significant decrease in ESPI in the developed regions than that in the undeveloped North and Northeast China. The results of this study could contribute to sustainable ecosystem management and decision-making for Chinese ecological civilization construction.


Cardiac surgery in patients with systemic lupus erythematosus.
Cardiac surgery was infrequently performed in patients with systemic lupus erythematosus (SLE), and its clinical outcome was reported only in small series. We sought to evaluate the clinical outcome of cardiac operation in patients with SLE. Between January 1996 and March 2005, 9 patients with SLE underwent cardiac surgery at the authors' hospital. Six patients underwent coronary artery bypass grafting (three conventional and three on-pump beating heart), two patients underwent valve replacement and 1 patient underwent simultaneous heart-kidney transplantation. All 6 patients with coronary artery bypass grafting had saphenous venous grafts and two of them had additional left internal mammary artery graft. The overall in-hospital mortality rate was 11% (1/9). Major postoperative complications occurred in 4 patients (44%) including profuse postoperative bleeding, ventricular tachycardia and early graft thrombosis. There were two late deaths including sudden cardiac death and sepsis. The median follow-up duration was 23 months (range, 1-110). In conclusion, although the postoperative complication was common, cardiac operation could be performed in patients with SLE.


High-fat foods overcome the energy expenditure induced by high-intensity cycling or running.
To examine the effects of two types of vigorous exercise [cycling (CYC) and running (RUN)] and diet composition on appetite control. Two studies using separate groups of subjects were used for the two forms of exercise. The studies used a 2 x 2 design with the factors being exercise and diet composition. Therefore both studies had four treatment conditions and used a repeated measures design. Both studies took place in the Human Appetite Research Unit at Leeds University. Twenty-four lean, healthy males were recruited from the student staff population of Leeds University. For both studies a control (no-exercise) and a vigorous exercise session (70% VO2 max) was followed by a free-selection lunch comprising high-fat/low-carbohydrate foods or low-fat/high-carbohydrate foods, during which energy and macronutrient intake was monitored. Motivation to eat was measured by visual analogue scales and by the latency to volitional onset of eating. Energy intake for the remainder of the day (outside of laboratory) was monitored by providing the subjects with airline-style food boxes. Both CYC and RUN produced similar effects on appetite responses. Both CYC and RUN induced a transitory suppression of hunger (P < 0.01 and P < 0.05) and a delay to the onset of eating (P < 0.001). Exercise (whether CYC or RUN) had no significant effect on the total amount of food eaten, but there was a significant effect of lunch type. When provided with the high-fat/low-carbohydrate foods energy intake was significantly elevated (CYC: P < 0.001; and RUN: P < 0.0001). Both types of exercise induced a short-term negative energy balance when followed by the low-fat/high-carbohydrate foods (P < 0.001), which was completely reversed (positive energy balance) when subjects ate from the high-fat/low carbohydrate foods. These results indicate that eating high-fat foods can prevent exercise inducing any (short-term) negative energy balance. Therefore, in order for exercise to have a significant impact on weight control, it is important to consider the energy density of the accompanying diet. Despite the different physiological aspects of cycling and running, they did not display different effects on appetite.


Apoptosis and p53 overexpression in human rectal cancer; relationship with response to hyperthermo-chemo-radiotherapy.
Hyperthermo-chemo-radio (HCR) therapy has been found to be effective for rectal cancer. Biomarkers for predicting the effect of HCR therapy are important in determining optimum treatment regimens. Hyperthermo-chemo-radiotherapy (HCR therapy), consisting of hyperthermia at 42 degrees C to 45 degrees C for 40 minutes (twice per week for two weeks), a total of 60 Gy irradiation and administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) (total 8400 mg), were prescribed pre-operatively for 29 patients with rectal cancer, using tissue specimens collected at pre-treatment biopsy. Apoptosis and overexpression of p53 protein were investigated histopathologically and immunohistochemically. On termination of HCR therapy, all the tumors were surgically resected and effectiveness of the therapy was evaluated histologically. Spontaneous apoptosis was evident in the pre-treatment cancer tissues of 14 patients (48.2%). In this apoptosis-positive group, the positive rate of expression of the p53 protein (21.4%, 3 out of 14) was lower as compared to findings in the apoptosis-negative group (66.7%, 10 out of 15). The response to HCR therapy was better in the apoptosis-positive group than in the apoptosis-negative group. We propose that spontaneous apoptosis is closely related to the function of wild-type p53 protein and is also a predictive biomarker of the effect of HCR therapy for patients with rectal cancer.


Mesoporous hollow spheres from soap bubbling.
The smaller and more stable bubbles can be generated from the large parent bubbles by rupture. In the presence of a bubble blowing agent, hollow spheres can be prepared by bubbling a silica sol. Herein, the trapped gas inside the bubble acts as a template. When the porogen, i.e., other surfactant, is introduced, a mesostructured shell forms by the co-assembly with the silica sol during sol-gel process. Morphological evolution emphasizes the prerequisite of an intermediate interior gas flow rate and high exterior gas flow rate for hollow spheres. The method is valid for many compositions from inorganic, polymer to their composites.


Correlation properties of heartbeat dynamics.
In this study, we investigate correlation properties of fluctuations in heart interbeat (RR) time series in a broad range of physiological and pathological conditions. Using detrended fluctuation analysis (DFA) method we determined short-term (alpha 1) and long-term (alpha 2) scaling exponent. In addition, we calculated standard deviation of RR intervals (SDRR) as the simplest variability measure. We found that the difference between alpha 1 and alpha 2 is related to RR interval length. At the shortest RR intervals, which correspond to extreme physiological and pathological conditions, we found the highest reduction of variability and the biggest difference between scaling exponents. In this case, DFA reveals a white noise over short scales (alpha 1 about 0.5) and strongly correlated noise over large scales (alpha 2 about 1.5). With an increase in RR interval, accompanied by increased variability (increase in parasympathetic control), the difference between alpha 1 and alpha 2 decreases. The difference between scaling exponents disappeared in a state of efficient autonomic control. We suggest that the complexity in heart rhythm is achieved through coupling between intrinsically controlled heart rhythm and autonomic control, and that the model of stochastic resonance mechanism could be applied to this system.


Psychologic and behavioral correlates of anorexia nervosa.
Female patients with anorexia nervosa (N = 34) were compared with two control groups of nonorganically ill, nonpsychotic female psychiatric patients. One control group was matched on several demographic variables; the other group was unmatched. Profiles on the Minnesota Multiphasic Personality Inventory indicated less psychologic disturbance among the anorectic patients than in the matched control sample, but more feelings of turmoil or distress than were reported in studies of adolescent medical patients and high school seniors. Anorectic patients were described by ward personnel as less physically capable and more timid than controls; they also displayed less heterosexual interest, interacted less often with both peers and staff, were viewed as being unhappier, and were described as expressing anger in relatively passive ways.


Human hybridoma suppressor factor (HSF) inhibits IL2 production in addition to suppressing immunoglobulin production.
The human thymus cell hybridoma, 8E-24, secretes a potent immunosuppressive factor(s), HSF, which inhibits polyclonal immunoglobulin (Ig) production. Our current studies reveal that this suppression is monocyte dependent in that its suppressive activity for Ig production was not observed in monocyte-depleted lymphocyte cultures but was restored by addition of monocytes. The requirement for monocytes was equally satisfied by autologous or allogeneic monocytes or monocyte conditioned media. Although the suppression mediated by HSF required the presence of monocytes, the mechanism for monocyte participation appears to be different from that reported for suppression mediated by soluble immune response suppressor (SIRS) in that general oxygen free radical scavengers did not inhibit this activity. Further information on the mechanism of action of HSF was obtained from studies on its suppressive effect on the phytohemagglutinin(PHA)-induced proliferative response. In this system HSF significantly suppressed PHA induced interleukin 2(IL2) production of peripheral blood mononuclear cells (PBMC) in a dose dependent fashion without inhibiting the proliferative response of CTLL-20 target cells to IL2. Interleukin 1 (IL1) production by monocyte cultures was also not suppressed by HSF. These results indicate that HSF interferes with IL2 production and not its induction by IL1 or its interaction with the IL2 receptor. To investigate the role of HSF-induced IL2 suppression in the pokeweed mitogen (PWM) antibody synthesis assay, the time course of IgG, IgM, IL1, and IL2 production of PWM stimulated PBMC cultures was examined. Results showed that the peak of IL2 production occurred on the second day of culture and was significantly suppressed by HSF while IL1 production was not affected during the seven day culture period. Similar suppression of IL2 and IgM production was observed in cultures of B cells and T4+ cells. Reconstitution of the IL2 levels in these cultures with recombinant IL2 completely restored antibody production. These results suggest that HSF in the presence of monocytes modulates the function of T4+ cells by inhibiting IL2 production. The inhibition of IL2 production by HSF appears to be responsible for the suppression of antibody production.


Analysis of the backbone dynamics of interleukin-1 beta using two-dimensional inverse detected heteronuclear 15N-1H NMR spectroscopy.
The backbone dynamics of uniformly 15N-labeled interleukin-1 beta are investigated by using two-dimensional inverse detected heteronuclear 15N-1H NMR spectroscopy. 15N T1, T2, and NOE data at a spectrometer frequency of 600 MHz are obtained for 90% of the backbone amide groups. The data provide evidence for motions on three time scales. All the residues exhibit very fast motions on a time scale of approximately less than 20-50 ps that can be characterized by a single-order parameter with an average value of 0.82 +/- 0.05. For a model comprising free diffusion within a cone, these residue-specific order parameters translate to an average cone semiangle of 20.7 +/- 3.3 degrees. Thirty-two residues also display motions on a time scale of 0.5-4 ns, slightly less than the overall rotational correlation time of the protein (8.3 ns). These additional motions must be invoked to account for the discrepancy between experiment and the simplest theoretical formulation in which the internal motions are described by only two parameters, a generalized order parameter and an effective correlation time [Lipari, G., & Szabo, A. (1982a) J. Am. Chem. Soc. 104, 4546-4559]. In particular, while the simple formulation can account for the 15N T1 and T2 data, it fails to account for the 15N-1H NOE data and yields calculated values for the NOEs that are either too small or negative, whereas the observed NOEs are positive. With the introduction of two internal motions that are faster than the rotational correlation time and differ in time scales by at least 1-2 orders of magnitude [Clore, G. M., Szabo, A., Bax, A., Kay, L. E., Driscoll, P. C., & Gronenborn, A. M. (1990) J. Am. Chem. Soc. 112, 4989-4991], all the relaxation data for these 32 residues can be fitted by two order parameters and an effective correlation time for the slower of the two internal motions. A simple model for these two motions is one in which the very fast motion involves axially symmetric diffusion within a cone, while the slower motion comprises jumps between two different orientations of the NH vector. For such a model the jump angle (excluding the C-terminal residue) ranges from 15 degrees to 69 degrees with a mean value of 28.6 +/- 14.0 degrees. Another 42 residues are characterized by some sort of motion on the 30-ns-10-ms time scale, which results in 15N line broadening due to chemical exchange between different conformational substates with distinct 15N chemical shifts.(ABSTRACT TRUNCATED AT 400 WORDS)