The fetal heart monitor tracing in pregnancies complicated by fetal thyrotoxicosis.
Fetal tachycardia caused by the transplacental passage of thyroid stimulating immunoglobulin is well established, but very little information exists regarding the fetal heart rate appearance of this form of tachycardia. Two cases of fetal tachycardia are described in pregnancies complicated by fetal thyrotoxicosis where maternal thyroid history was unknown at the time of testing. For each pregnancy, the fetal heart monitor tracing is depicted and described. In both cases, the initial fetal heart rate pattern demonstrated a sustained baseline of 170 to 180 beats per minute with moderate variability that exhibited accelerations with a lack of decelerations. The tracings were essentially normal except for the baseline rate. When reviewing the differential for fetal tachycardia presenting in the antenatal period, this pattern is unique to fetal thyrotoxicosis, especially if the mother is afebrile and there is no history of medication usage that could explain this presentation.


Frontiers of optofluidics in synthetic biology.
The development of optofluidic-based technology has ushered in a new era of lab-on-a-chip functionality, including miniaturization of biomedical devices, enhanced sensitivity for molecular detection, and multiplexing of optical measurements. While having great potential, optofluidic devices have only begun to be exploited in many biotechnological applications. Here, we highlight the potential of integrating optofluidic devices with synthetic biological systems, which is a field focusing on creating novel cellular systems by engineering synthetic gene and protein networks. First, we review the development of synthetic biology at different length scales, ranging from single-molecule, single-cell, to cellular population. We emphasize light-sensitive synthetic biological systems that would be relevant for the integration with optofluidic devices. Next, we propose several areas for potential applications of optofluidics in synthetic biology. The integration of optofluidics and synthetic biology would have a broad impact on point-of-care diagnostics and biotechnology.


Irregular nocturnal breathing patterns high altitude in subjects susceptible to high-altitude pulmonary edema (HAPE): a preliminary study.
We studied nocturnal breathing patterns and symptoms of acute mountain sickness (AMS) during trekking in the Japanese Alps (altitude: 2,760-2,920 m) for 4 d in five subjects susceptible to high-altitude pulmonary edema (HAPE-S-S) and five control volunteers. Breathing patterns were evaluated with the impedance plethysmograph, and symptoms of AMS were evaluated by the environmental symptoms questionnaire-III score for AMS of cerebral type (AMS-C score). In both groups, the percentage of time with periodic breathing significantly increased at high altitude and the percentage in controls was significantly higher than in HAPE-S-S on the second night. In four HAPE-S-S, other disordered breathing patterns, termed "irregular breathing," were observed frequently by night at high altitude. Irregular breathing patterns were characterized by irregularly repeated oscillatory or nonoscillatory clusters of breaths with augmented tidal volume, followed by expiratory pause, apnea, or hypoventilation of various durations. All controls did not show significant changes in AMS-C score, but four HAPE-S-S showed the increase in AMS-C score on the next morning after frequent irregular nocturnal breathing. There was significant correlation between the percentage of time with irregular nocturnal breathing and AMS-C score on the next morning. These results suggest that HAPE-S-S are prone to irregular nocturnal breathing patterns at high altitude, which is associated with the development of AMS, but it was not possible to determine whether these abnormal breathing patterns are a cause or an effect of AMS.


Parametric elastic analysis of coupled helical coils for tubular implant applications: experimental characterization and numerical analysis.
Coupled helical coils show promising mechanical behavior to be used as tubular organ constructs, e.g., in trachea or urethra. They are potentially easy to manufacture by filament winding of biocompatible and resorbable polymers, and could be tailored for suitable mechanical properties. In this study, coupled helical coils were manufactured by filament winding of melt-extruded polycaprolactone, which was reported to demonstrate desired in vivo degradation speed matching tissue regeneration rate. The tensile and bending stiffness was characterized for a set of couple helical coils with different geometric designs, with right-handed and left-handed polymer helices fused together in joints where the filaments cross. The Young's modulus of unidirectional polycaprolactone filaments was characterized, and used as input together with the structural parameters of the coupled coils in finite element simulations of tensile loading and three-point bending of the coils. A favorable comparison of the numerical and experimental results was found, which paves way for use of the proposed numerical approach in stiffness design under reversible elastic conditions of filament wound tubular constructs.


A minimal model for human whole body cholesterol metabolism.
Important work by others has shown that human whole body cholesterol metabolism can be described by a three-compartment model computed from plasma cholesterol specific activity after an intravenous infusion of labeled cholesterol. However, some parameters of that model cannot be estimated precisely [coefficient of variation (CV) 15-19% after 40 wk of follow-up], making its use in routine clinical investigation difficult. On the other hand, a simpler two-compartment model can be calculated with excellent precision from only 10 wk of data (CV 2-8%), but its parameters are inaccurate (for example, the size of the central pool is overestimated by 20%, and the rate constant for fractional excretion of cholesterol from the body is underestimated by 15%). Thus both three-compartment and two-compartment models of cholesterol turnover have important limitations. An alternative is provided by a minimal model that takes advantage of the increased precision expected in the solution of models with fewer parameters. A three-compartment structure is used, but only four (rather than 6 or more) parameters are calculated: the mass of the rapidly mixing central cholesterol compartment, the fractional rate of cholesterol elimination from the body, and the average forward and reverse rate constants for cholesterol transfer between the rapid compartment and both slower compartments. Each of these parameters can be determined unambiguously (without the need to use a minimum or maximum estimate), accurately (mean values within 2% of theory), and with precision (CV 3-13%).(ABSTRACT TRUNCATED AT 250 WORDS)


Why is medical school difficult? Or, if it isn't difficult, why it should be.
Given the intellect and motivation of the idealized contemporary medical student and the structure of contemporary medical education, one might not expect medical school to be difficult; experience dictates otherwise. Since medical school prepares one to become a physician, the inherent difficulty of medical school is expected to lie in the areas of the physician's attitudes, skills, and knowledge. This expectation is not supported; instead it is suggested that the difficulty may actually reside in the fact that the student must negotiate three different learning styles in the course of only two years.


Optical and Physicochemical Properties of Brown Carbon Aerosol: Light Scattering, FTIR Extinction Spectroscopy, and Hygroscopic Growth.
A great deal of attention has been paid to brown carbon aerosol in the troposphere because it can both scatter and absorb solar radiation, thus affecting the Earth's climate. However, knowledge of the optical and chemical properties of brown carbon aerosol is still limited. In this study, we have investigated different aspects of the optical properties of brown carbon aerosol that have not been previously explored. These properties include extinction spectroscopy in the mid-infrared region and light scattering at two different visible wavelengths, 532 and 402 nm. A proxy for atmospheric brown carbon aerosol was formed from the aqueous reaction of ammonium sulfate with methylglyoxal. The different optical properties were measured as a function of reaction time for a period of up to 19 days. UV/vis absorption experiments of bulk solutions showed that the optical absorption of aqueous brown carbon solution significantly increases as a function of reaction time in the spectral range from 200 to 700 nm. The analysis of the light scattering data, however, showed no significant differences between ammonium sulfate and brown carbon aerosol particles in the measured scattering phase functions, linear polarization profiles, or the derived real parts of the refractive indices at either 532 or 402 nm, even for the longest reaction times with greatest visible extinction. The light scattering experiments are relatively insensitive to the imaginary part of the refractive index, and it was only possible to place an upper limit of k ≤ 0.01 on the imaginary index values. These results suggest that after the reaction with methylglyoxal the single scattering albedo of ammonium sulfate aerosol is significantly reduced but that the light scattering properties including the scattering asymmetry parameter, which is a measure of the relative amount of forward-to-backward scattering, remain essentially unchanged from that of unprocessed ammonium sulfate. The optical extinction properties in the mid-IR range (800 to 7000 cm(-1)) also showed no significant changes in either the real or the imaginary parts of the refractive indices for brown carbon aerosol particles when compared to ammonium sulfate. Therefore, changes in the optical properties of ammonium sulfate in the mid-IR spectral range due to reaction with methylglyoxal appear to be insignificant. In addition to these measurements, we have characterized additional physicochemical properties of the brown carbon aerosol particles including hygroscopic growth using a tandem-differential mobility analyzer. Compared to ammonium sulfate, brown carbon aerosol particles are found to have lower deliquescence relative humidity (DRH), efflorescence relative humidity (ERH), and hygroscopic growth at the same relative humidities. Overall, our study provides new details of the optical and physicochemical properties of a class of secondary organic aerosol which may have important implications for atmospheric chemistry and climate.


PhenoHM: human-mouse comparative phenome-genome server.
PhenoHM is a human-mouse comparative phenome-genome server that facilitates cross-species identification of genes associated with orthologous phenotypes (http://phenome.cchmc.org; full open access, login not required). Combining and extrapolating the knowledge about the roles of individual gene functions in the determination of phenotype across multiple organisms improves our understanding of gene function in normal and perturbed states and offers the opportunity to complement biologically the rapidly expanding strategies in comparative genomics. The Mammalian Phenotype Ontology (MPO), a structured vocabulary of phenotype terms that leverages observations encompassing the consequences of mouse gene knockout studies, is a principal component of mouse phenotype knowledge source. On the other hand, the Unified Medical Language System (UMLS) is a composite collection of various human-centered biomedical terminologies. In the present study, we mapped terms reciprocally from the MPO to human disease concepts such as clinical findings from the UMLS and clinical phenotypes from the Online Mendelian Inheritance in Man knowledgebase. By cross-mapping mouse-human phenotype terms, extracting implicated genes and extrapolating phenotype-gene associations between species PhenoHM provides a resource that enables rapid identification of genes that trigger similar outcomes in human and mouse and facilitates identification of potentially novel disease causal genes. The PhenoHM server can be accessed freely at http://phenome.cchmc.org.


Mitochondrial substrate availability and its role in lipid-induced insulin resistance and proinflammatory signaling in skeletal muscle.
The relationship between glucose and lipid metabolism has been of significant interest in understanding the pathogenesis of obesity-induced insulin resistance. To gain insight into this metabolic paradigm, we explored the potential interplay between cellular glucose flux and lipid-induced metabolic dysfunction within skeletal muscle. Here, we show that palmitate (PA)-induced insulin resistance and proinflammation in muscle cells, which is associated with reduced mitochondrial integrity and oxidative capacity, can be attenuated under conditions of glucose withdrawal or glycolytic inhibition using 2-deoxyglucose (2DG). Importantly, these glucopenic-driven improvements coincide with the preservation of mitochondrial function and are dependent on PA oxidation, which becomes markedly enhanced in the absence of glucose. Intriguingly, despite its ability to upregulate mitochondrial PA oxidation, glucose withdrawal did not attenuate PA-induced increases in total intramyocellular diacylglycerol and ceramide. Furthermore, consistent with our findings in cultured muscle cells, we also report enhanced insulin sensitivity and reduced proinflammatory tone in soleus muscle from obese Zucker rats fed a 2DG-supplemented diet. Notably, this improved metabolic status after 2DG dietary intervention is associated with markedly reduced plasma free fatty acids. Collectively, our data highlight the key role that mitochondrial substrate availability plays in lipid-induced metabolic dysregulation both in vitro and in vivo.


Nuclear magnetic resonance studies of 6-fluorotryptophan-substituted rat cellular retinol-binding protein II produced in Escherichia coli. Analysis of the apoprotein and the holoprotein containing bound all-trans-retinol and all-trans-retinal.
Rat cellular retinol-binding protein II (CRBP II) is a 15.6-kDa intestinal protein which binds all-trans-retinol and all-trans-retinal but not all-trans-retinoic acid. We have previously analyzed the interaction of Escherichia coli-derived rat apoCRBP II with several retinoids using fluorescence spectroscopic techniques. Interpretation of these experiments is complicated, because the protein has 4 tryptophan residues. To further investigate ligand-protein interactions, we have utilized 19F nuclear magnetic resonance (NMR) spectroscopy of CRBP II labeled at its 4 tryptophan residues with 6-fluorotryptophan. Efficient incorporation of 6-fluorotryptophan (93%) was achieved by growing a tryptophan auxotroph of E. coli harboring a prokaryotic expression vector with a full-length rat CRBP II cDNA on defined medium supplemented with the analog. Comparison of the 19F NMR spectra of 6-fluorotryptophan-substituted CRBP II with and without bound all-trans-retinol revealed that resonances corresponding to 2 tryptophan residues (designated WA and WB) undergo large downfield changes in chemical shifts (2.0 and 0.5 ppm, respectively) associated with ligand binding. In contrast, 19F resonances corresponding to two other tryptophan residues (WC and WD) undergo only minor perturbations in chemical shifts. The 19F NMR spectra of 6-fluorotryptophan-substituted CRBP II complexed with all-trans-retinal and all-trans-retinol were very similar, suggesting that the interactions of these two ligands with the protein are similar. Molecular model building, based on the crystalline structures of two homologous proteins was used to predict the positions of the 4 tryptophan residues of CRBP II and to make tentative resonance assignments. The fact that ligand binding produced residue-specific changes in the chemical shifts of resonances in CRBP II suggests that NMR analysis of isotopically labeled retinoid-binding proteins expressed in E. coli will provide an alternate, albeit it complementary, approach to fluorescence spectroscopy for examining the structural consequences of their association with ligand.


[Results of conservative or substitutive surgical treatment in mitral valve prolapse caused by redundant cusps].
Between October 1969 and October 1979 120 patients (78 males and 42 females, mean age 48 years) underwent surgical correction of floppy mitral valve at Harefield Hospital. Family history of mitral valve disease was present in 3 patients and 6 had skeletal manifestations of Marfan syndrome. The presenting symptom was shortness of breath in 110 (92%), chest pain in 18 (15%), and palpitations in 29 (24%). Thirty-two patients had more than one symptom. A history of bacterial endocarditis was obtained from 18 patients. At the time of operation 88% of the patients were in class III-IV NYHA. Forty-five patients had mitral valve replacement and the remaining 75 had a conservative procedure. Findings at operation were: rupture of posterior chordae in 72 (60%); rupture of anterior chordae in 15 (13%); rupture of anterior and posterior chordae in 6 and elongation of chordae without rupture in 27 (22%). Hospital mortality for isolated replacement was 6.5%. Twenty-seven patients (22%) died subsequently (mean follow-up of 75 months). Hospital mortality for repair was 3.2% and late mortality mean follow-up 34 months) was 6.5%. Sixty-seven patients are asymptomatic and 21 are improved. A conservative approach to floppy mitral valve disease has been adopted in all patients since 1974 and has given better early and late results compared to valve replacement.


Epstein-Barr virus regulates the life cycle and host cell biology by hijacking post-translational modification.
Protein post-translational modifications (PTMs) are reversible processes that regulate the function of target proteins without altering their sequences. High-throughput sequencing surveys have provided insights into the patterns of PTMs, such as ubiquitination, SUMOylation, and phosphorylation. After primary infection, the Epstein-Barr virus (EBV), a ubiquitous herpesvirus, establishes a life-long latent infection. EBV can establish a delicate balance to regulate its proliferation and host cell survival. Owing to the limited gene products of EBV, interfering with the host PTM machinery is an effective way to alter host immune responses and physiological status and establish infection. In this review, we focus on the current knowledge of the mechanisms by which EBV products manipulate host ubiquitination, SUMOylation, and phosphorylation to establish a latent infection or favour viral replication and pathogenesis.


Twist1 is a key regulator of cancer-associated fibroblasts.
Cancer-associated fibroblasts (CAF) are key contributors to malignant progression, but their critical regulators remain largely unknown. In this study, we examined the role of Twist1, a central regulator of epithelial-mesenchymal transition in carcinoma cells, in the transdifferentiation of normal quiescent fibroblasts to CAF and we defined its upstream controls and downstream effectors. Primary human gastric fibroblast and CAF cultures were established from gastrectomy specimens and validated as nontumor cells by somatic mutation analyses. In these cultures, exposure to the proinflammatory cytokine IL6 commonly expressed in tumors was sufficient to induce Twist1 expression in normal fibroblasts and transdifferentiate them into CAFs via STAT3 phosphorylation. In xenograft models, tumor infiltration of Twist1-expressing CAFs was enhanced strongly by ectopic IL6 expression in gastric or breast cancer cells. We found that Twist1 expression was necessary and sufficient for CAF transdifferentiation. Enforced expression of Twist1 in normal fibroblasts was also sufficient to drive CAF marker expression and malignant character in gastric cancer cells both in vitro and in vivo. Conversely, silencing the expression of Twist1 in CAFs abrogated their tumor-promoting properties. Downstream of Twist1, we defined the chemokine CXCL12 as a transcriptional target. Clinically, CXCL12 and Twist1 expression were correlated in CAFs present in gastric tumor specimens. Finally, ectopic expression of Twist1 in normal fibroblasts suppressed premature senescence, whereas Twist1 attenuation accelerated senescence in CAFs. Our findings define Twist1 as a compelling target to deprogram the tumor-supporting features of the cancer microenvironment.


A statistical evaluation of the fixed dose procedure.
The Fixed Dose Procedure (FDP) was first proposed in 1984 by the British Toxicology Society, as an alternative to the conventional LD50 test (OECD Test Guideline 401), for determining acute oral toxicity. The FDP used fewer animals and caused less suffering than the LD50 test, and provided information on acute toxicity which allowed substances to be classified according to the European Union hazard classification system. In 1992, the FDP was introduced as OECD Test Guideline 420. In 1999, as part of an initiative to phase out Test Guideline 401, a review of the FDP was undertaken. The aim of the review was to provide further reductions and refinements, and classification according to the criteria of the Globally Harmonised Hazard Classification and Labelling Scheme. The revised FDP was adopted by the OECD in 2001. This article concerns the development and revision of the FDP. It illustrates how statistical modelling and simulation can be used to increase the efficiency of a test procedure and reduce the number of animals needed for an in vivo validation of the procedure.


CRS1 is a novel group II intron splicing factor that was derived from a domain of ancient origin.
Protein-dependent group II intron splicing provides a forum for exploring the roles of proteins in facilitating RNA-catalyzed reactions. The maize nuclear gene crs1 is required for the splicing of the group II intron in the chloroplast atpF gene. Here we report the molecular cloning of the crs1 gene and an initial biochemical characterization of its gene product. Several observations support the notion that CRS1 is a bona fide group II intron splicing factor. First, CRS1 is found in a ribonucleoprotein complex in the chloroplast, and cofractionation data provide evidence that this complex includes atpF intron RNA. Second, CRS1 is highly basic and includes a repeated domain with features suggestive of a novel RNA-binding domain. This domain is related to a conserved free-standing open reading frame of unknown function found in both the eubacteria and archaea. crs1 is the founding member of a gene family in plants that was derived by duplication and divergence of this primitive gene. In addition to its previously established role in atpF intron splicing, new genetic data implicate crs1 in chloroplast translation. The chloroplast splicing and translation functions of crs1 may be mediated by the distinct protein products of two crs1 mRNA forms that result from alternative splicing of the crs1 pre-mRNA.


The pathological and clinical features of anterior lesions of prostate cancer: Evaluation in a single cohort of patients.
The aim of our work is to evaluate the principal differences of the pathological features in prostate cancer (PCa) lesions comparing those in the anterior region of the gland (APCa) to those in the posterior zone (PPCa) among patients who underwent to robotic-assisted radical prostatectomy (RP). A total of 85 consecutive patients (mean age 66; IQR 62-71) with clinically suspected PCa were studied with multiparametric magnetic resonance of prostate before prostate biopsies. The prostate biopsies were RM-guided (60 inbore biopsy (MR-GB) and 25 Fusion-biopsy (FB). A total of 72 cases were eligible for robotic RP. An experienced genitourinary pathologist reviewed the histopathology of the tissue specimens of the patients after RP. The exclusion criteria were as follows: previous hormonotherapy, radiotherapy and chemotherapy for others cancers. Based on the histological diagnosis, after RP, 68 anterior prostate cancer, and 107 posterior lesions were found. We further subcategorized lesions into peripheral and central zones for each the anterior and posterior lesions. The specific distribution of lesions by pathologic stage was: T2 = 74 (42.3%), T3a = 87 (49.7%), T3b = 12 (6.9%), T4 = 2 (1.1%) cases. Tumor volume of posterior neoplasms ranged from 0.04 to 20.35 cm3, with a median of 3.39 cm3. Anterior tumor volume ranged from 0.17 to 15 cm3, with a median volume of 2.54 cm3: PPCa were larger than APCa but the difference in size was not significant. The prostate cancer grade group (GG) I was distributed as 16.6% and 36% in anterior and posterior lesions cases. GG II and III was 43.8% and 31.5% in anterior and posterior cases, respectively. Comparatively, GG IV-V showed 39.6% and 32.5% for anterior and posterior lesions respectively (p < 0.001). Extraprostatic extention of neoplasm (EPE) was found more frequently in anterior cases (31.4%) than in in posterior cases (25.1%), but without significant difference. Lymphovascular invasion was similar in both the groups: 24% and 28.6% in anterior and posterior group, respectively. Anterior lesions showed a significantly higher rate of lymph node metastasis (9.3%) than posterior lesions (3.4%) (p < 0.005). In our study, we have found EPE, often associated with worse prognosis, more frequently (but not significantly) present in anterior lesions among PCa patients. Although posterior lesions are often related to pT3b stage, in our findings, anterior lesions were more often associated with a more aggressive neoplasm with more frequent nodal involvements.


Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study.
We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced expiratory volume in 1 s (FEV(1)) <60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month. Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV(1) % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7-0.8 (p<0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1-1.2 (p<0.001)). The effect of season was independent of these risk factors. COPD exacerbations and hospitalisations were more frequent in winter.


Comparison perception of singular transcranial magnetic stimuli by subjectively electrosensitive subjects and general population controls.
Transcranial magnetic stimulation of the dorsolateral prefrontal cortex by single pulses of varying field intensities was used to measure thresholds of individual perception and motor response in three groups of subjects: subjectively electrosensitive people, general population controls with a high burden of complaints related to electromagnetic field (EMF) exposure in the literature (highest decile in complaint burden), and general population controls with a low burden of complaints (lowest decile in complaint burden). The major study endpoint was the ability of the subjects to differentiate between real magnetic stimulation and a sham condition. There were no significant differences between groups in the thresholds, neither of detecting the real magnetic stimulus nor in motor response. But the three groups differed significantly in differentiating between stimulation and sham condition, with the subjectively electrosensitive people having the lowest ability to differentiate and the control group with high level of EMF-related complaints having the best ability to differentiate. Differences between groups were mostly due to false alarm reactions in the sham condition reported by subjectively electrosensitives (SES). We found no objective correlate of the self perception of being "electrosensitive." Overall, our experiment does not support the hypothesis that subjectively electrosensitive patients suffer from a physiological hypersensitivity to EMFs or stimuli. Further research should focus on disposing factors explaining the unspecific sensory hyperresponsiveness of subjectively electrosensitive subjects.


[The computer in nursing education--analysis of the attitudes of students of university schools].
This study aims at identifying and analyzing the attitudes by students from different institutions regarding the use of the computer in Nursing teaching. Methodology consisted in the elaboration, application and analysis of Likert scales distributed among students of the eighth semester in higher education institutions at the cities of Ribeirão Preto and Bauru. Results indicated the computer as one of the main resources for nursing teaching and the simulation as an excellent bridge between theory and practice as well as the educational softwares useful and interesting. Authors verified the high level of interest and positive attitudes regarding the employment of computer resources in nursing teaching.


Healthcare resource utilization and costs of major atherothrombotic vascular events among patients with peripheral artery disease after revascularization.
Peripheral artery disease (PAD), often treated with lower extremity revascularization, is associated with risk of major atherothrombotic vascular events (acute limb ischemia [ALI], major non-traumatic lower-limb amputation, myocardial infarction [MI], ischemic stroke, cardiovascular death). This study aims to assess healthcare resource utilization and costs of such events among patients with PAD after revascularization. Patients aged ≥50 years with PAD who were treated with lower-extremity revascularization were identified from Optum Clinformatics Data Mart claims database (01/2014-06/2019). The first lower extremity revascularization after PAD diagnosis was defined as the index date. Patients had ≥6 months of health plan enrollment before the index date. Patients were followed until the earliest of 1) end of enrollment or data; 2) diagnosis of atrial fibrillation or venous thromboembolism; or 3) oral anticoagulant use. All-cause healthcare resource use per-patient-year was compared before and after a major atherothrombotic vascular event post-revascularization among those with an event. Additionally, event-related healthcare costs per-patient-year were reported for each event type. Of the 38,439 PAD patients meeting the study criteria, 6,675 (17.4%) had a major atherothrombotic vascular event. On average, patients were observed for 7.3 months before an event and 6.2 months after an event. Patients with an event had significantly higher all-cause healthcare resource use versus similar metrics pre-event (e.g. inpatient visits among those with ALI: 3.5 ± 5.8 post-event vs. 2.0 ± 8.1 pre-event, p < .05). Event-related costs ranged from $57,825±$131,810 per-patient-year for ischemic stroke to $108,302±$150,168 for major non-traumatic lower-limb amputation. Data do not contain clinical information. Additionally, results are limited to commercially insured and Medicare Advantage beneficiaries. Patients with PAD who experience major atherothrombotic vascular events post-revascularization have considerably higher healthcare resource use and costs compared with similar metrics pre-event. Therefore, reducing the rate of such events could reduce overall healthcare costs for this population.


Quantitative analyses of relationships between ecotoxicological effects and combined pollution.
The responses of wheat Triticum aestivum, rice Oryza sativa, earthworms Eisenia foetida, and prawns Penaeus japonicus to combined acetochlor-Cu, Cd-Zn were studied in hydroponic and soil-culturing systems using the methods of ecotoxicology. In particular, systematically quantitative analyses were documented by field experiments. Results showed that ecotoxicological effects under the combined pollution were not only related to chemical properties of pollutants but also dependent on the concentration level of pollutants, in particular on the combination of concentrations of pollutants in ecosystems. Additionally, species of organisms, especially the type of ecosystem, determined the influences. To some extent, biological tissue targets attacked by pollutants were an important factor.


Effects of mean airway pressure and tidal volume on lung and chest wall mechanics in the dog.
Dependencies of the dynamic mechanical properties of the respiratory system on mean airway pressure (Paw) and the effects of tidal volume (VT) are not completely clear. We measured resistance and dynamic elastance of the total respiratory system (Rrs and Ers), lungs (RL and EL), and chest wall (Rcw and Ecw) in six healthy anesthetized paralyzed dogs during sinusoidal volume oscillations at the trachea (50-300 ml; 0.4 Hz) delivered at mean Paw from -9 to +23 cmH2O. Changes in end-expiratory lung volume, estimated with inductance plethysmographic belts, showed a typical sigmoidal relationship to mean Paw. Each dog showed the same dependencies of mechanical properties on mean Paw and VT. All elastances and resistances were minimal between 5 and 10 cmH2O mean Paw. All elastances, Rrs, and RL increased greatly with decreasing Paw below 5 cmH2O. Ers and EL increased above 10 cmH2O. Ecw, Ers, Rcw, and Rrs decreased slightly with increasing VT, but RL and EL were independent of VT. We conclude that 1) respiratory system impedance is minimal at the normal mean lung volume of supine anesthetized paralyzed dogs; 2) the dependency of RL on lung volume above functional residual capacity is dependent on VT and respiratory frequency; and 3) chest wall, but not lung, mechanical behavior is nonlinear (i.e., VT dependent) at any given lung volume.


Safety of Exercise Testing in the Clinical Chinese Population.
This 18-year cross-sectional study was conducted to provide data on the safety of exercise testing in the clinical Chinese population. We retrospectively identified exercise tests completed at Xiangya Hospital of Central South University from January 1, 2002 to December 31, 2019. From 43,130 unique individuals (50.9% female), a total of consecutive 50,142 tests (standard exercise testing 29,466; cardiopulmonary exercise testing 20,696) were retrieved. Demographics, patients' medical history, exercise testing characteristics, and exercise testing-related adverse events were described. Safety data is expressed as the number of adverse events per 10,000 tests, with 95% confidence interval. The average patients' age was 51 ± 13 years. The majority of patients were diagnosed with at least one disease (N = 44,941, 89.6%). Tests were maximal or symptom-limited. Common clinical symptoms included dizziness (6,822, 13.6%), chest pain or distress (2,760, 5.5%), and musculoskeletal limitations (2,507, 5.0%). Out of 50,142 tests, three adverse events occurred, including one sustained ventricular tachycardia, one sinus arrest with junctional escape rhythm at a rate of 28 bpm, and one syncopal event with fecal and urinary incontinence. The rate of adverse events was 0.8 events per 10,000 tests (95% confidence interval, 0.2-3.0) in men, 0.4 per 10,000 tests (0.7-2.2) in women, and 0.6 per 10,000 tests (0.21.8) total. This study represents the largest dataset analysis of exercise testing in the clinical Chinese population. Our results demonstrate that clinical exercise testing is safe, and the low rate of adverse events related to exercise testing might be due to the overall changes in clinical practice over time.


T2*-weighted magnetic resonance imaging with hyperoxia in acute ischemic stroke.
We describe the first clinical application of transient hyperoxia ("oxygen challenge") during T2*-weighted magnetic resonance imaging (MRI), to detect differences in vascular deoxyhemoglobin between tissue compartments following stroke. Subjects with acute ischemic stroke were scanned with T2*-weighted MRI and oxygen challenge. For regions defined as infarct core (diffusion-weighted imaging lesion) and presumed penumbra (perfusion-diffusion mismatch [threshold = T(max) > or =4 seconds], or regions exhibiting diffusion lesion expansion at day 3), T2*-weighted signal intensity-time curves corresponding to the duration of oxygen challenge were generated. From these, the area under the curve, gradient of incline of the signal increase, time to maximum signal, and percentage signal change after oxygen challenge were measured. We identified 25 subjects with stroke lesions >1ml. Eighteen subjects with good quality T2*-weighted signal intensity-time curves in the contralateral hemisphere were analyzed. Curves from the diffusion lesion had a smaller area under the curve, percentage signal change, and gradient of incline, and longer time to maximum signal (p < 0.05, n = 17) compared to normal tissue, which consistently showed signal increase during oxygen challenge. Curves in the presumed penumbral regions (n = 8) showed varied morphology, but at hyperacute time points (<8 hours) showed a tendency to greater percentage signal change. Differences in T2*-weighted signal intensity-time curves during oxygen challenge in brain regions with different pathophysiological states after stroke are likely to reflect differences in deoxyhemoglobin concentration, and therefore differences in metabolic activity. Despite its underlying complexities, this technique offers a possible novel mode of metabolic imaging in acute stroke.


A clinical approach to computerized perimetry.
Computerized perimeters have increased the precision with which visual fields may be tested. The purpose of this paper is to present considerations for properly performing automated perimetry. Selecting the correct perimeter to complement specific practices is discussed, and various test strategies available on automated perimeters are reviewed. Selection of the appropriate program to provide the clinician with the information needed is essential. A step-by-step discussion as to proper performance of automated perimetry includes factors that should be considered so that consistency between visual field examinations can be maintained. Confounding variables, such as the learning effect, pupil size, and various ocular pathologies, are discussed with respect to their effects on automated perimetric results.


Architectural dynamics of the meiotic spindle revealed by single-fluorophore imaging.
Bipolarity of the meiotic spindle, required for proper chromosome segregation, is maintained throughout cell division despite rapid microtubule turnover. How this is achieved has remained mysterious, as determining the organization of individual spindle microtubules has been difficult. Here, we develop single-fluorophore speckle imaging to examine microtubule organization in the vertebrate meiotic spindle. We find that the mean length of microtubules is approximately 40% of spindle length. Long and short filaments distribute randomly throughout the spindle and those in close proximity can move in the same direction with highly heterogeneous velocities. The ratio between microtubule and spindle lengths remains unchanged as spindles elongate upon dynein-dynactin inhibition. However, maintaining this ratio depends on proper kinesin-5 function. Our data suggest that force transmission within the spindle must be understood in terms of the crosslinking dynamics of a tiled array of individual filaments, most of which do not span the distance from the pole to the metaphase plate.


Tryptophan depletion and the kinase GCN2 mediate IFN-γ-induced autophagy.
IFN-γ is a master regulator of the immune responses that occur in the transplanted kidney, acting both on the immune system and on the graft itself. The cellular responses to IFN-γ are complex, and emerging evidence suggests that IFN-γ may regulate autophagic functions. Conversely, autophagy modulates innate and adaptive immune functions in various contexts. In this study, we identify a novel mechanism by which IFN-γ activates autophagy in human kidney epithelial cells and provide new insights into how autophagy regulates immune functions in response to IFN-γ. Our results indicate that IFN-γ promotes tryptophan depletion, activates the eIF2α kinase general control nonderepressible-2 (GCN2), and leads to an increase in the autophagic flux. Further, tryptophan supplementation and RNA interference directed against GCN2 inhibited IFN-γ-induced autophagy. This process is of functional relevance because autophagy regulates the secretion of inflammatory cytokines and growth factors by human kidney epithelial cells in response to IFN-γ. These findings assign to IFN-γ a novel function in the regulation of autophagy, which, in turn, modulates IFN-γ-induced secretion of inflammatory cytokines.


Onyx extrusion through the scalp after embolization of dural arteriovenous fistula.
A man in his sixties referred with symptoms of episodic left lip numbness and left arm weakness was diagnosed with a Borden type 3 dural arteriovenous fistula (DAVF) on DSA. Successful Onyx embolization of the DAVF was performed via the distal left occipital artery using an ev3 Apollo detachable tip microcatheter. He underwent surgical obliteration for the residual DAVF 3 days later. Three months later during a routine postoperative clinic visit, the patient produced a plastic bag containing multiple small pieces of Onyx cast and the detached tip of the Apollo microcatheter that had extruded out from his scalp through small spontaneous holes about 5 weeks after the embolization procedure. This spontaneous extrusion of Onyx can be alarming to the patient not expecting it; however, prior knowledge and discussion can lessen the anxiety of both the treating physician and the patient dealing with such a situation.


A retrospective and prospective analysis of the west African Ebola virus disease epidemic: robust national health systems at the foundation and an empowered WHO at the apex.
The Ebola virus disease outbreak in west Africa is pivotal for the worldwide health system. Just as the depth of the crisis ultimately spurred an unprecedented response, the failures of leadership suggest the need for innovative reforms. Such reforms would transform the existing worldwide health system architecture into a purposeful, organised system with an empowered, highly capable WHO at its apex and enduring, equitable national health systems at its foundation. It would be designed not only to provide security against epidemic threats, but also to meet everyday health needs, thus realising the right to health. This retrospective and prospective analysis offers a template for these reforms, responding to the profound harms posed by fragile national health systems, delays in the international response, deficient resource mobilisation, ill defined responsibilities, and insufficient coordination. The scope of the reforms should address failures in the Ebola response, and entrenched weaknesses that enabled the epidemic to reach its heights.


The lateral leeway in the habitual intercuspation: experimental studies and literature review.
The habitual intercuspation is used ubiquitous for manufacturing small dental restorations. However, a little is known on its precision. The aim of the present study was therefore to investigate the unambiguity and accuracy of the habitual occlusion in mounted plaster casts from fully dentate persons. Eighty-one fully dentate volunteers, 36 women and 45 men aged 26.8 +/- 6.2 years (18-55 years), with minor fillings and no signs or symptoms of TMD took part in the experiments. Silicone impressions were taken, poured with stone plaster and the obtained casts mounted into Dentatus ARL(R)- articulators using an individual face bow transfer. Subsequently, the models were transferred to a custom-made measuring articulator where the lateral leeway and the accuracy of the hand-held habitual intercuspation were quantified in the condylar area. Measurements were repeated seven times with the upper cast pushed either to the maximum right or the maximum left intercuspation. The hand-held habitual intercuspation of upper and lower cast proved ambiguous in 57% of pairs of casts. The average lateral leeway of the habitual intercuspation in the condylar area was 0.10 +/- 0.05 mm (0-0.51 mm; median 0.07 mm) between the maximum right and left occlusal positions. The average accuracy of three repeated measurements was 0.22 +/- 0.09 mm (0.02-1.17 mm; median 0.16 mm). Natural occlusal surfaces in a full dentition do not guarantee an unambiguous habitual intercuspation of the plaster casts. The described leeway and technical limits might be possible causes for occlusal adjustments that are sometimes necessary when inserting restorations manufactured in habitual intercuspation.


Antigenic markers of V domain of mouse MOPC 21 IgG1 L chain. The conformational basis of VL domain markers and content of MOPC 21 VL-like immunoglobulins in sera of inbred mouse strains.
Antisera were raised in rabbits against L chains, isolated from mouse myeloma protein MOPC21 (gamma 1, chi V chi 15 group). Specific antibodies for the V and C domain of MOPC21 L chain were obtained by cross-immunoadsorption of the antisera. The pure anti-V and anti-C antibodies were fixed on diazocellulose and used as immunosorbents. The inhibitory capacity of L chin-monomers and dimers isolated from the L chain preparation was compared to that of intact IgG1 using binding inhibition of 125I-labeled IgG1 on the antibody-containing immunosorbents. It was established that changes of IgG1 quaternary structure influences the conformational state of the L chain V domain only. The inhibitory capacity of the V domain is 1000-fold lower in L monomers, if compared with native IgG1, and only 10-fold lower than in L dimers. The inhibiting capacity of the C domain, however, does not differ in L monomers and intact IgG1. Thus the conformational rigidity of the C domain co-exists with conformational flexibility of the V domain on the same polypeptide chain. We tried to estimate the content of MOPC21 V1-like normal IgG in mouse serum of 6 inbred strains using antibodies against the V1 domain. Data obtained by inhibition of radioimmunoadsorption, indicate that in C57BL/6 mice 0.08% of normal serum Ig carries a V1 region which is idiotypically related to the V1 of MOPC21. In serum Ig of BALB/c mice the percentage is 0.16.


A novel approach allows identification of K channels in the lateral membrane of rat CCD.
We have developed a novel approach to study K channels in the lateral membrane of principal cells (PC) in rat cortical collecting ducts (CCD). The technique consists of 1) exposing the CCD apical membrane, 2) removing the intercalated cells adjoining a PC by gentle suction through a pipette, and 3) applying patch-clamp technique to the lateral membrane of PC. Functional viability of the PC was confirmed by three indexes: 1) maintenance of physiological cell membrane potentials (-85 +/- 3 mV); 2) depolarization of the cell membrane potential with 1 mM Ba2+; and 3) hyperpolarization of the cell potential with 0.1 mM amiloride. Two types of K channels were identified: a low-conductance K channel and an intermediate-conductance K channel. In cell-attached patches the slope conductance of the low-conductance K channel was 27 pS and that of the intermediate-conductance K channel was 45 pS. The open probability (Po) of the 27-pS K channel was 0.81 +/- 0.02 and was not voltage dependent. In contrast, the Po of the 45-pS K channel was 0.23 +/- 0.01 at the spontaneous cell membrane potential and was increased by hyperpolarization. In addition, decrease of the bath pH from 7.4 to 6.7 reduced the 27-pS K channel current amplitude in a voltage-dependent manner, but the Po was not affected. Finally, two time constants were required to fit open- and closed-time histograms of both populations of K channels. Application of 1 mM Ba2+ completely blocked these K channels. We conclude that two types of K channel are present in the basolateral membrane of PC.


Effect of yoga on polycystic ovarian syndrome: A systematic review.
Polycystic Ovarian Syndrome (PCOS) is not a disease but a mere syndrome. Many researchers have studied polycystic ovarian syndrome and found that there is no proper cause of that, it may occur due to hormonal imbalance or stress, or due to a sedentary lifestyle. The rate of polycystic ovarian syndrome in Indian women has been increasing rapidly. The symptoms include acne, weight gain, hirsutism, difficulties in fertility, irregular or infrequent periods, immature ovarian eggs that do not ovulate, multiple cysts in the ovary. If left untreated, it may become the cause for heart diseases, diabetes, hypertension, infertility, and even cancer. There are varieties of medical treatments available to treat polycystic ovarian syndrome but they have a temporary effect and if taken for a long time then it may lead to serious side effects. Yoga has proven effects in reducing and managing the symptoms of polycystic ovarian syndrome more effectively along with medicine. This review work has been designed to consider the available literature concerning the effectiveness of yoga in the management of the polycystic ovarian syndrome. It includes some research papers published between 2012 and 2019. By providing yogic treatment effect on several parameters (such as blood lipid level, glucose metabolism, endocrine parameters, quality of life, resting cardiovascular parameters, level of anxiety, depression) on the woman with polycystic ovarian syndrome were measured. After thoroughly studying about 74 research papers, 16 are found most relevant to be reviewed. The studies of these papers concluded the successful use of different yogic limbs for the management of polycystic ovarian syndrome with or without medications.


High quality imaging and dosimetry for yttrium-90 (90Y) liver radioembolization using a SiPM-based PET/CT scanner.
Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres is a liver-directed treatment for primary and secondary hepatic malignancies. Personalized dosimetry aims for maximum treatment effect and reduced toxicity. We aimed to compare pre-treatment voxel-based dosimetry from 99mTc macroaggregated albumin (MAA) SPECT/CT with post-treatment 90Y PET/CT for absorbed dose values, and to evaluate image quality of 90Y SiPM-based PET/CT. Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planning 99mTc-MAA SPECT/CT and post-therapy 90Y PET/CT were assessed. 90Y PET/CT images were acquired for 20 min and reconstructed to produce 5-, 10-, 15-, and 20-min datasets, then evaluated using the 5-point Likert scale. The mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from 99mTc-MAA SPECT/CT and 90Y PET/CT were 175.69 ± 113.76 Gy and 193.58 ± 111.09 Gy (P = 0.61), respectively for glass microspheres; they were 60.18 ± 42.20 Gy and 70.98 ± 49.65 Gy (P = 0.37), respectively for resin microspheres. The mean normal liver absorbed doses from 99mTc-MAA SPECT/CT and 90Y PET/CT were 32.70 ± 22.25 Gy and 30.62 ± 20.09 Gy (P = 0.77), respectively for glass microspheres; they were 18.33 ± 11.08 Gy and 24.32 ± 15.58 Gy (P = 0.17), respectively for resin microspheres. Image quality of 90Y PET/CT at 5-, 10-, 15-, and 20-min scan time showed a Likert score of 3.6 ± 0.54, 4.57 ± 0.58, 4.84 ± 0.37, and 4.9 ± 0.3, respectively. 99mTc-MAA SPECT/CT demonstrated great accuracy for treatment planning dosimetry. SiPM-based PET/CT scanner showed good image quality at 10-min scan time, acquired in one bed position. A PET/CT scan time of 5 min showed acceptable image quality and suffices for dosimetry and treatment verification. This allows for inclusion of 90Y PET/CT in busy routine clinical workflows. Studies with larger patient cohorts are needed to confirm these findings.


The NCI-60 Methylome and Its Integration into CellMiner.
A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (∼21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and miRNA transcripts, DNA copy number, and protein levels. Here, we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2.0 (https://discover.nci.nih.gov/cellminer). Among new insights, transcript versus DNA methylation correlations revealed the epithelial/mesenchymal gene functional category as being influenced most heavily by methylation. DNA methylation and copy number integration with transcript levels yielded an assessment of their relative influence for 15,798 genes, including tumor suppressor, mitochondrial, and mismatch repair genes. Four forms of molecular data were combined, providing rationale for microsatellite instability for 8 of the 9 cell lines in which it occurred. Individual cell line analyses showed global methylome patterns with overall methylation levels ranging from 17% to 84%. A six-gene model, including PARP1, EP300, KDM5C, SMARCB1, and UHRF1 matched this pattern. In addition, promoter methylation of two translationally relevant genes, Schlafen 11 (SLFN11) and methylguanine methyltransferase (MGMT), served as indicators of therapeutic resistance or susceptibility, respectively. Overall, our database provides a resource of pharmacologic data that can reinforce known therapeutic strategies and identify novel drugs and drug targets across multiple cancer types. Cancer Res; 77(3); 601-12. ©2016 AACR.


Implementation of a process-orientated multidisciplinary approach (POMA), a system of cost-effective healthcare delivery within a cardiac surgical unit.
The process-orientated multidisciplinary approach (POMA) is a means of delivering consultant-led healthcare from the first outpatient clinic visit through to discharge, bringing together clinical and operational management that can result in effective resource utilisation and improved patient care. Prospectively collected data from patients undergoing primary isolated coronary artery bypass graft (CABG) were collected before and after the application of POMA (246 and 260 patients, respectively). The impact of POMA was analysed on the number of cancellations (NOC), postoperative clinical incidents (POCI), postoperative length of stay (PLOS) and cost in the practice of one consultant surgeon. Data were obtained from our clinical database (PATS-Dendrite), which is used risk stratify patients and prospectively to collect clinical/operative data and outcomes. Patients were matched for all variables except for the European Cardiac Surgical Risk Score (EuroSCORE) which was 1.93 for pre-POMA patients and 2.73 for post-POMA patients (p<0.05). Cancellations significantly decreased from 4.5% (n = 11, pre-POMA) to 0.4% (n = 1, post-POMA) (p<0.05). POCI significantly decreased from 44.3% (n = 109, pre-POMA) to 36.2% (n = 94, post-POMA) (p<0.05). PLOS significantly decreased from 6.3 (pre-POMA) to 6.1 days (post-POMA) (p = 0.002). Regression analysis showed that implementation of POMA was the only significant factor in the reduction of POCI and PLOS (p<0.05). POMA resulted in an overall saving of 285,868 pound (400,215 euro; US $508,845) calculated using the 2005 National Health Service (NHS) tariffs. The implementation of POMA was the only significant known (or measured) factor that improved the operational efficiency and clinical outcome of a single surgeon's practice. The authors believe the principles deserve to be studied further to see if the results can be replicated.


Dysfunctional HDL: from structure-function-relationships to biomarkers.
Reduced plasma levels of HDL-C are associated with an increased risk of CAD and myocardial infarction, as shown in various prospective population studies. However, recent clinical trials on lipid-modifying drugs that increase plasma levels of HDL-C have not shown significant clinical benefit. Notably, in some recent clinical studies, there is no clear association of higher HDL-C levels with a reduced risk of cardiovascular events observed in patients with existing CAD. These observations have prompted researchers to shift from a cholesterol-centric view of HDL towards assessing the function and composition of HDL particles. Of importance, experimental and translational studies have further demonstrated various potential antiatherogenic effects of HDL. HDL has been proposed to promote macrophage reverse cholesterol transport and to protect endothelial cell functions by prevention of oxidation of LDL and its adverse endothelial effects. Furthermore, HDL from healthy subjects can directly stimulate endothelial cell production of nitric oxide and exert anti-inflammatory and antiapoptotic effects. Of note, increasing evidence suggests that the vascular effects of HDL can be highly heterogeneous and HDL may lose important anti-atherosclerotic properties and turn dysfunctional in patients with chronic inflammatory disorders. A greater understanding of mechanisms of action of HDL and its altered vascular effects is therefore critical within the context of HDL-targeted therapies.


The Association of Clinical Symptoms and Coexistent Clinical Conditions with Ophthalmic Manifesting in COVID-19 Patients.
The ocular symptoms are common manifestations in coronavirus infectious disease 2019 (COVID-19), which faces secondary complications and therapeutic challenges. Underlying diseases actuate the body to infectious diseases and their related manifestations through the aberration of metabolism and suppressing the immune system. This study aimed to investigate the correlation of underlying diseases and ocular manifestations in COVID-19 patients. This cross-sectional study was held on 108 hospitalized COVID-19 patients (confirmed by molecular detection) admitted to Rouhani hospital, Babol, Iran. Upon hospitalization, all clinical symptoms and underlying diseases were registered. Detailed clinical examinations regarding ophthalmological protocols were used to investigate the ocular symptoms. All analyses were performed by SPSS, version 25. Our results showed that 26.67% of patients with at least one ocular symptom had hyperlipidemia, while 10.42% of patients without any ocular symptoms had hyperlipidemia (P=0.049). In this study, 97.81% of COVID-19 patients without epiphora had no thyroid disorders (hyper-/hypo-thyroidism), while 82.35% of COVID-19 patients with epiphora had not any thyroid disorders (P=0.012). Also, 75.00% of patients with blurred vision had diabetes mellitus, while 35.00% of patients without blurred vision suffered from diabetes mellitus. This difference was borderline significant (P=0.051). Other results showed that 13.04% of COVID-19 patients with eye redness suffer from myalgia, while 35.29% of patients without eye redness had myalgia (P=0.044). Also, 35.11% of COVID-19 patients without photophobia had myalgia, while none of the patients with photophobia had myalgia (P=0.005). Finally, 70.00% of patients with respiratory distress had at least one ocular symptom, while 43.10% of patients without respiratory distress had at least one ocular symptom (P=0.007). Some underlying diseases, e.g., hyperlipidemia, diabetes mellitus, and thyroid disorders, and some clinical symptoms in hospitalized patients, e.g., myalgia and respiratory distress, are correlated with ocular manifestations in COVID-19 patients.


Subcellular distribution of superoxide dismutases in human neutrophils. Influence of myeloperoxidase on the measurement of superoxide dismutase activity.
We have identified two distinct pools of superoxide dismutase in fractions of human peripheral neutrophils obtained by the isopycnic fractionation of homogenates of the latter with linear sucrose gradients. Superoxide dismutase activity, observed with polyacrylamide gels impregnated with Nitro Blue Tetrazolium, was present in: (1) the mitochondrial fraction [density (rho) 1.169g/ml], containing the high-molecular-weight KCN-resistant enzyme, and (2) the cytoplasm fraction, containing the low-molecular-weight KCN-sensitive enzyme. Superoxide dismutase activity, observed with a quantitative assay involving cytochrome c, was present in: (1) the mitochondria, (2) the cytoplasm, and (3) the azurophil-granule fractions (rho=1.206 and 1.222g/ml). No substantial enzyme activity was observed in specific-granule fractions (rho=1.187g/ml) or in the membranous fraction (rho=1.136g/ml) in either assay. The apparent superoxide dismutase activity observed in the azurophil granules with the cytochrome c assay was attributable not to true superoxide dismutase but to myeloperoxidase, an enzyme found solely in the azurophil granules. In the presence of H(2)O(2), human neutrophil myeloperoxidase oxidized ferrocytochrome c. Thus, in the cytochrome c assay for superoxide dismutase, the oxidation of ferrocytochrome c by myeloperoxidase mimicked the inhibition of reduction of ferricytochrome c by superoxide dismutase. When myeloperoxidase was removed from azurophilgranule fractions by specific immuno-affinity chromatography, both myeloperoxidase and apparent superoxide dismutase activities were removed. It is concluded that there is no detectable superoxide dismutase in either the azurophil or specific granules of human neutrophils. Mitochondrial superoxide dismutase, 15% of the total dismutase activity of the cells, occurred only in fractions of density 1.160g/ml, where isocitrate dehydrogenase and cytochrome oxidase were also observed.


Molecular insight into conformational transformation of human glucokinase: conventional and targeted molecular dynamics.
Glucokinase (GK) plays a key role in the regulation of hepatic glucose metabolism. An unusual mechanism of positive cooperativity of monomeric GK containing only a single binding site for glucose is very interesting and still unclear. The activation process of GK is associated with a large-scale conformational change from the inactive to the active state. Here, conventional and targeted molecular dynamics simulations were used to study the conformational dynamics of GK in the stable configurations and in the transition from active to inactive state. Three phases of the structural reorganization of GK were detected. The first step is a transformation of GK from the active state to the intermediate structure, where the cleft between the domains is open, but alpha helix 13 is still inside the small domain. From this point, there are two alternative paths. One path leads to the inactive state through the release of helix 13 from the inside of small domain to the outside. Other path goes back to the active state. Simulation results reveal the critical role of helix 13 in the transformation of GK from the open state to inactive one and the influence of the loop 2 on the protein transformation between the open and the closed active states. Principal component analysis and covariance matrix analysis were carried out to analyze the dynamics of protein. Importance of hydrogen bonds in the stability of the closed conformation is shown. Overall, our simulations provide new information about the dynamics of GK and its structural transformation.Communicated by Ramaswamy H. Sarma.


Incidence and risk factors for paclitaxel hypersensitivity during ovarian cancer chemotherapy.
Hypersensitivity reaction (HSR) is still a major concern during cancer chemotherapy with paclitaxel. In the present study, we investigated retrospectively the incidence of HSRs to paclitaxel and the risk factors in 105 patients (553 courses) who received adjuvant chemotherapy (paclitaxel and carboplatin) for ovarian cancer. Moderate to severe HSRs that led to cessation or discontinuation of the chemotherapy, including respiratory distress and hypotension, were observed in 14 patients (13.3%) and 16 courses (2.9%), regardless of the use of conventional premedication with glucocorticoid, and histamine H(1) and H(2) antagonists. The incidence of HSRs to paclitaxel in patients with ovarian cancer seemed to be considerably higher than those reported by other investigators in patients with other carcinomas such as non-small-cell lung cancer and breast cancer. Four risk factors were identified: (1) history of mild dermal reactions such as facial flushing and urticaria in previous courses, (2) presence of respiratory dysfunction, (3) obesity (body mass index >25), and (4) postmenopausal at the time of ovariectomy. The incidence of hypersensitivity increased linearly as the number of risk factors increased (r=0.992, P=0.008). It is likely that disappearance of the estrous cycle facilitates the occurrence of HSRs to paclitaxel.


A Smoking Prevention Intervention Among Young People in an Online Community Game: Results from a Pilot Randomized Controlled Trial.
Background: Innovative methods for smoking prevention interventions need to be investigated to increase attractiveness, access hard-to-reach populations, and increase effectiveness. We studied the feasibility and immediate effects of an intervention to reinforce norms and behaviors of young people related to antismoking, integrated into a popular online community game. Methods: A pilot randomized controlled trial was conducted through the HABBO online community. The intervention group was exposed to repeated discussion sessions with small groups of peer players and two facilitators once a week for 1 month (four sessions), inside the game. The control group had access to antismoking information websites. Process indicators (attractiveness, participation) and immediate outcomes (norms and intentions with regard to smoking) were assessed by questionnaire. Results: One hundred sixteen players were invited to participate in the intervention; 10 did not meet eligibility criteria, 30 were allocated to the intervention group, and 76 to the control group. Median age was 23. Twenty-four percent were not in education, employment, or training. A median of eight players attended each session and the median number of exchange chats by session was 399; 70% of chat time was occupied by the players. Twenty players attended all four sessions. Immediate norms, representations, and intentions were evaluated in 39 players and showed small differences between groups. Conclusion: Delivering and evaluating a smoking prevention intervention in an online game is feasible. In the targeted online community game, the intervention was attractive and allowed the delivery of innovative interventions to audiences with diverse social profiles. Long-term effects, sustainability, and evaluation methodology are discussed.


Sacrificial Labour: Social Inequality, Identity Work, and the Damaging Pursuit of Elusive Futures.
This article explores the relationship between personal sacrifice and identity work within conditions of profound structural insecurity. We develop the concept of sacrificial labour to describe how individual self-sacrifice aligns workers' identities to the needs of organizations while gradually foreclosing the actualization of individuals' desired future selves. Drawing upon qualitative data from a longitudinal study of healthy individuals who enrol in paid clinical trials for the pharmaceutical industry, we make two contributions to the identity-work literature. First, we argue that the ongoing project of building stable and secure identities may become damaging when structural and cultural conditions defy even provisional, fragile attainment of this goal. Second, we reflect on how racialization and social marginalization erode identities and constrain possibilities for identity recuperation. Whereas the identity-work literature often focuses on the agential accomplishments of individuals, we provide a troubling account of how persistent social and economic inequalities confound identity realization efforts.


Orexins/hypocretins excite basal forebrain cholinergic neurones.
The orexins (orexin A and B, also known as hypocretin 1 and 2) are two recently identified neuropeptides (de Lecea et al., 1998; Sakurai et al., 1998) which are importantly implicated in the control of wakefulness (for reviews see Hungs and Mignot, 2001; van den Pol, 2000; Willie et al., 2001 ). Indeed, alteration in these peptides' precursor, their receptors or the hypothalamic neurones that produce them leads to the sleep disorder narcolepsy (Chemelli et al., 1999; Lin et al., 1999; Peyron et al., 2000; Thannickal et al., 2000). The mechanisms by which the orexins modulate wakefulness, however, are still unclear. Their presence in fibres coursing from the hypothalamus (Peyron et al., 1998) up to the preoptic area (POA) and basal forebrain (BF) suggests that they might influence the important sleep and waking neural systems situated there (Jones, 2000). The present study, performed in rat brain slices, demonstrates, however, that the orexins have no effect on the GABA sleep-promoting neurones of the POA, whereas they have a strong and direct excitatory effect on the cholinergic neurones of the contiguous BF. In addition, by comparing the effects of orexin A and B we demonstrate here that orexins' action depends upon orexin type 2 receptors (OX(2)), which are those lacking in narcoleptic dogs (Lin et al., 1999). These results suggest that the orexins excite cholinergic neurones that release acetylcholine in the cerebral cortex and thereby contribute to the cortical activation associated with wakefulness.


Research ethics in a pandemic: considerations for the use of research infrastructure and resources for public health activities.
The number and size of existing research studies with massive databases and biosample repositories that could be leveraged for public health response against SARS-CoV-2 (or other infectious disease pathogens) are unparalleled in history. What risks are posed by coopting research infrastructure-not just data and samples but also participant recruitment and contact networks, communications, and coordination functions-for public health activities? The case of the Seattle Flu Study highlights the general challenges associated with utilizing research infrastructure for public health response, including the legal and ethical considerations for research data use, the return of the results of public health activities relying upon research resources to unwitting research participants, and the possible impacts of public health reporting mandates on future research participation. While research, including public health research, is essential during a pandemic, careful consideration should be given to distinguishing and balancing the ethical mandates of public health activities against the existing ethical responsibilities of biomedical researchers.


The expression of the adenovirus 12 early region 1B 19K protein using a recombinant simian virus 40 system.
Using a simian virus 40/adenovirus 12 (Ad12)-recombinant virus, the Ad12 early region 1B (E1B) 19K protein has been produced at high levels after infection of Cos 1 cells. Expression of the 19K polypeptide reaches a maximum at about 48 h post-infection, declining at later times as host cell death occurs. Using two-dimensional isoelectric focusing/SDS-polyacrylamide gel electrophoresis, we have shown that the Ad12 E1B protein is a major species following infection of Cos 1 cells with recombinant virus. Two forms of 19K polypeptide can be distinguished following isoelectric focusing. Using subcellular fractionation of infected cells, it was found that a similar distribution of 19K protein occurred after recombinant virus and Ad12 infection, with the polypeptide being most abundant in nuclear and membranous fractions. Similarly, as in Ad12-infected cells, a certain proportion of the protein is located on the outside surface of the cell after recombinant viral infection. Immunohistochemical studies suggest that, at early times post-infection, the E1B 19K protein is located in the nuclear membrane, the Golgi apparatus and the endoplasmic reticulum. At later times, it can be seen to have spread to the cytoplasm as well as to the other organelles. These results are discussed in relation to the known functions of the 19K E1B protein.


Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer.
Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic-binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-galactosylceramide (α-GalCer)-induced NKT cell activation in a dose-dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the antitumor NKT cell response as an early mechanism of tumor immune evasion.


Effect of magnesium chloride and guanidinium chloride on the extraction of components of extracellular matrix from chicken cartilage.
In order to evaluate the effect of chaotropic agents on proteoglycan and non-collagenous proteins, chicken xiphoid cartilage was treated with guanidine-HCl and MgCl2 in different concentrations (1M to 5M), and different periods of time (12, 24, 48 and 72 hr). The maximum yield of uronic acid was obtained with 3M MgCl2 (73.3%). Concentrations of 4M and 5M of MgCl2 showed that much less uronic acid was removed, 55.3% and 38.1% respectively. Extraction with 3M MgCl2 and 3M guanidine-HCl resulted better efficiency when performed for 48 hr. Analysis by SDS-PAGE of the extracts obtained with guanidine-HCl and MgCl2 in different concentrations pointed out that most components are equally removed with the two solvents, showing that the extraction with MgCl2 is an alternative assay to remove non-collagenous proteins from extracellular matrix.


Influence of ball possession and playing position on the physical demands encountered during professional basketball games.
Understanding the game demands encountered in basketball provides useful insight for developing specific, individualized and team-based training sessions. This study quantified and compared the game activity demands encountered by basketball players of different playing positions: i) strictly when in possession of the ball and ii) overall during live playing time (irrespective of ball possession). The activity demands encountered by 44 (22 guards, 14 forwards, 8 centres) adult, professional, male basketball players were assessed across 10 official games. Time-motion analysis was used to determine the frequency and proportion (%) of playing time performing recovery (REC), low- (LIA), moderate- (MIA), and high- (HIA) intensity activities. Linear mixed models were constructed to examine differences in dependent variables between playing positions, accounting for repeated measures. Guards, forwards, and centres spent 11.9±5.9%, 3.5±1.3%, and 2.9±1.1% of live playing time in possession of the ball, respectively. Guards performed more activities at all intensities (total movements, REC, LIA, MIA, and HIA) than forwards (P < 0.05) and centres (P < 0.05) when in possession of the ball. The proportion of time spent performing HIA in possession of the ball was greater for forwards (P = 0.001) and centres (P = 0.001) than guards. During live playing time overall across games, centres performed more HIA per minute (P = 0.049) and spent a greater proportion of time performing HIA (P = 0.047) than guards. Activities performed when in possession of the ball and during live playing time across basketball games are affected by playing position. These data highlight the need to develop position-specific training drills, particularly with ball possession.


Treatment strategy to optimize radiofrequency ablation for liver malignancies.
The purposes of this study were to investigate a treatment strategy to increase liver tumor necrosis and minimize complications with ultrasound-guided percutaneous radiofrequency (RF) ablation and to evaluate its therapeutic efficacy. A total of 332 patients with 503 liver malignancies underwent RF ablation according to a mathematical protocol with adjunctive measures. In the 332 patients, 205 had 308 hepatocellular carcinomas (HCCs) with a mean largest diameter of 4.1 cm and 127 had 195 metastatic liver carcinomas (MLCs) with a mean largest diameter of 3.9 cm. In patients with HCC, 60 (29.3%) had stage I/II disease and 145 (70.7%) had stage III/IV disease. Depending on tumor size, shape, and location, a defined treatment strategy was adopted that consisted of a mathematical protocol, an individualized protocol, and adjunctive measures. The mathematical protocol was followed for tumors larger than 3.5 cm. The individualized protocol was used for tumors located adjacent to the diaphragm, gastrointestinal tract, or gallbladder. Some adjunctive measures such as supplementary fine needle localization, local saline solution injection, and feeding vessel ablation were used to deal with different features of these liver tumors. Patients were followed regularly to assess treatment efficiency, and the tumor was considered to have early complete necrosis if no viability was found on enhanced computed tomography 1 month after RF ablation. In this series, the early necrosis rates were 95.8% for HCC (295 of 308 tumors), 94.9% for MLC (185 of 195 tumors), 91.3% for tumors larger than 3.5 cm (189 of 207 tumors), 90.7% for tumors near the gastrointestinal tract (49 of 54 tumors), 91.5% for tumors near the diaphragm (86 of 94 tumors), and 90.6% for tumors near the gallbladder (48 of 53 tumors). The local recurrence rates were 10.7% for HCC (33 of 308 tumors) and 14.9% for MLC (29 of 195 tumors). The 1-, 2-, and 3-year overall survival rates were 89.6%, 69.4%, and 59.6%, respectively, for HCC and 80.3%, 52.8%, and 30.9%, respectively, for MLC. The 1-, 2-, and 3-year survival rates in 60 patients with stage I/II HCC were 93.7%, 87.1%, and 76.2%, respectively. The incidence of major complications was 1.4% (eight of 574 sessions), which included of three hemorrhages, four injuries to adjacent structures, and one case of needle tract seeding. In RF ablation of hepatic tumors, application of a proper protocol and adjunctive measures play important roles in improving tumor necrosis rate and minimizing potential complications.


The global distribution of Lyme disease.
Following the original description of erythema chronicum migrans (ECM) in Sweden in 1909, ECM became widely recognized in Europe. The first reported case of ECM acquired in the United States occurred in 1969, and in 1975 the full symptom complex now known as Lyme disease was recognized. In 1981, cases of Lyme disease were recognized in yet a third continent, Australia and, to date, cases acquired in at least 19 countries have been reported. Beginning with the original case reported in Sweden, clinical observations suggested that Ixodes ricinus ticks were a vector for ECM in Europe and the distribution of cases in Europe corresponds to the distribution of this tick, although one case outside this range has been reported following mosquito bites. Through similar observations, I. dammini and I. pacificus ticks have been established as vectors in the United States. In Australia, a vector has not been established, and none of the recognized vectors of Lyme disease occur there. The reporting of cases of Lyme disease from widely separated parts of the world involving multiple vectors suggests the disease may, in the future, be recognized in additional areas.


[Dietary energy density and associated factors: how is the population of Sao Paulo doing?].
To evaluate dietary energy density in adults living in Sao Paulo and associated factors. Subjects were participants of ISA-Capital study, which was carried out with probabilistic sampling (n = 710 adults). Food consumption was assessed by R24h. Correlations with dietary constituents were evaluated using Pearson's correlation coefficient. Associations with demographic, socioeconomic and lifestyle data were investigated by multivariate regression models. The average energy density was 1.98 kcal/g (95% CI [1.94, 2.01]). It was positively correlated with energy, fat, carbohydrate, cholesterol, saturated fat, sucrose, trans fat and added sugar intake; and negatively correlated with fiber intake. Only age and smoking were associated with energy density. High values of energy density and the relationship determined with other nutritional constituents denote the poor quality of the diet in this population, which may be contributing to the rising rates of overweight.


In vivo conditions induce faithful encoding of stimuli by reducing nonlinear synchronization in vestibular sensory neurons.
Previous studies have shown that neurons within the vestibular nuclei (VN) can faithfully encode the time course of sensory input through changes in firing rate in vivo. However, studies performed in vitro have shown that these same VN neurons often display nonlinear synchronization (i.e. phase locking) in their spiking activity to the local maxima of sensory input, thereby severely limiting their capacity for faithful encoding of said input through changes in firing rate. We investigated this apparent discrepancy by studying the effects of in vivo conditions on VN neuron activity in vitro using a simple, physiologically based, model of cellular dynamics. We found that membrane potential oscillations were evoked both in response to step and zap current injection for a wide range of channel conductance values. These oscillations gave rise to a resonance in the spiking activity that causes synchronization to sinusoidal current injection at frequencies below 25 Hz. We hypothesized that the apparent discrepancy between VN response dynamics measured in in vitro conditions (i.e., consistent with our modeling results) and the dynamics measured in vivo conditions could be explained by an increase in trial-to-trial variability under in vivo vs. in vitro conditions. Accordingly, we mimicked more physiologically realistic conditions in our model by introducing a noise current to match the levels of resting discharge variability seen in vivo as quantified by the coefficient of variation (CV). While low noise intensities corresponding to CV values in the range 0.04-0.24 only eliminated synchronization for low (<8 Hz) frequency stimulation but not high (>12 Hz) frequency stimulation, higher noise intensities corresponding to CV values in the range 0.5-0.7 almost completely eliminated synchronization for all frequencies. Our results thus predict that, under natural (i.e. in vivo) conditions, the vestibular system uses increased variability to promote fidelity of encoding by single neurons. This prediction can be tested experimentally in vitro.


Multiparameter Analysis Using 18F-FDG PET/CT in the Differential Diagnosis of Pancreatic Cystic Neoplasms.
To evaluate multiparametric analysis in differential diagnosis between pancreatic serous cystic neoplasms (SCNs) and mucinous cystic neoplasms (MCNs) as well as the differentiation of the benign and malignant MCNs with 18F-FDG (18-fluorodeoxyglucose) PET/CT (positron emission tomography). Forty patients with total of 41 lesions (SCNs: 27/41; MCNs: 14/41), who were preoperatively examined with 18F-FDG PET/CT, were retrospectively analyzed. Multiple quantitative parameters using conventional and texture features were included. The combined model was established with complementary PET/MR parameters. The differential diagnostic efficacy of each independent parameter and the combined model were evaluated with receiver operating characteristic (ROC) analysis. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI) were used to evaluate improvement of diagnostic efficacy by using combination of multiple parameters. Among all independent parameters, the percentile 5th (0.88 ± 0.38 vs 0.47 ± 0.23, P < 0.001) showed the highest discriminative diagnostic value. The combination of multiple parameters can improve the differential diagnostic efficacy of SCNs and MCNs (sensitivity = 71.4%, specificity = 77.8%, and AUC = 0.788), and the addition of texture parameters to the conventional parameters allowed a significant reclassification with IDI = 0.236 (95% CI: 0.095-0.377) and categorical NRI = 0.434 (95% CI: 0.030-0.838). SURmax (tumor to normal pancreas ratio, T/P) and SURmax (tumor to aorta ratio, T/A) both showed the highest discriminative diagnostic value (sensitivity = 100.0%, specificity = 70.0%, AUC = 0.900, and Youden index = 0.700) in the differential diagnosis of benign and malignant MCNs, with the cutoff values of 0.84 and 0.90, respectively. Combination of multiple parameters using 18F-FDG PET/CT could further improve differentiation between pancreatic SCNs and MCNs. SURmax (T/P) and SURmax (T/A) could improve differential diagnosis of benign and malignant MCNs.


Components of Torpedo electric organ and muscle that cause aggregation of acetylcholine receptors on cultured muscle cells.
The synaptic portion of a muscle fiber's basal lamina sheath has molecules tightly bound to it that cause aggregation of acetylcholine receptors (AChRs) on regenerating myofibers. Since basal lamina and other extracellular matrix constituents are insoluble in isotonic saline and detergent solutions, insoluble detergent-extracted fractions of tissues receiving cholinergic input may provide an enriched source of the AChR-aggregating molecules for detailed characterization. Here we demonstrate that such an insoluble fraction from Torpedo electric organ, a tissue with a high concentration of cholinergic synapses, causes AChRs on cultured chick muscle cells to aggregate. We have partially characterized the insoluble fraction, examined the response of muscle cells to it, and devised ways of extracting the active components with a view toward purifying them and learning whether they are similar to those in the basal lamina at the neuromuscular junction. The insoluble fraction from the electric organ was rich in extracellular matrix constituents; it contained structures resembling basal lamina sheaths and had a high density of collagen fibrils. It caused a 3- to 20-fold increase in the number of AChR clusters on cultured myotubes without significantly affecting the number or size of the myotubes. The increase was first seen 2-4 h after the fraction was added to cultures and it was maximal by 24 h. The AChR-aggregating effect was dose dependent and was due, at least in part, to lateral migration of AChRs present in the muscle cell plasma membrane at the time the fraction was applied. Activity was destroyed by heat and by trypsin. The active component(s) was extracted from the insoluble fraction with high ionic strength or pH 5.5 buffers. The extracts increased the number of AChR clusters on cultured myotubes without affecting the number or degradation rate of surface AChRs. Antiserum against the solubilized material blocked its effect on AChR distribution and bound to the active component. Insoluble fractions of Torpedo muscle and liver did not cause AChR aggregation on cultured myotubes. However a low level of activity was detected in pH 5.5 extracts from the muscle fraction. The active component(s) in the muscle extract was immunoprecipitated by the antiserum against the material extracted from the electric organ insoluble fraction. This antiserum also bound to extracellular matrix in frog muscles, including the myofiber basal lamina sheath. Thus the insoluble fraction of Torpedo electric organ is rich in AChR-aggregating molecules that are also found in muscle and has components antigenically similar to those in myofiber basal lamina.


The Effect of Live-Video Demonstration on Dental Students' Orthodontic Bending Performance.
The aims of this study were to evaluate the effects of a live-video teaching tool on the performance of dental students in bending an orthodontic vestibular arch and to assess the students' perceptions of the technology. All 135 fourth-year dental students in the 2018 academic year at Hacettepe Dental School, Ankara, Turkey, were invited to participate in the study; after exclusions, the remaining 116 were randomly divided into two demonstration cohorts. These students had no prior experience bending an orthodontic wire. Cohort 1 (control, N=58) was shown a conventional live demonstration of the orthodontic bending of a vestibular arch, and Cohort 2 (experimental, N=58) was shown a live-video demonstration of the same procedure. Both cohorts saw the demonstration before beginning the exercise and were evaluated afterwards on their performance of the procedure. In addition, the students' perceptions of the demonstration techniques were collected with a questionnaire. The results did not show any significant differences in the students' bending scores between the control and experimental cohorts (p=0.767). The median values on the questionnaire indicated almost no statistically significant difference in responses between the cohorts. The only significant difference was that Cohort 1 had a higher percentage who answered "yes" they would like to rewatch the demonstration than did Cohort 2 (p=0.024). In this study, the live-video technique was found to be as effective as a conventional live demonstration for orthodontic practical education, suggesting that either technique could be used as an appropriate method for training in orthodontic wire bending.


Vasomotor control by subretrofacial neurones in the rostral ventrolateral medulla.
In this paper we review our recent work in the rabbit and cat on the role of the rostral ventrolateral medulla in cardiovascular regulation. Microinjection of neuroexcitatory amino acids into a highly circumscribed region, located just ventral to the retrofacial nucleus at the level of the rostral part of the inferior olive, leads to an increase in blood pressure, owing to sympathetic vasoconstriction. Bilateral destruction of this region, which we have termed the subretrofacial nucleus, leads to a profound fall in blood pressure. Anatomical studies show that the subretrofacial nucleus contains a compact group of bulbospinal neurones that project to sympathetic preganglionic nuclei in the thoracolumbar spinal cord. Single-unit recording studies have shown that these bulbospinal neurons are spontaneously active and are powerfully inhibited by baroreceptor inputs. These observations indicate that the subretrofacial bulbospinal cells are sympathoexcitatory and play a major role in the tonic and phasic control of the cardiovascular system. Some important unresolved questions regarding the subretrofacial neurones will be discussed. (i) Are they functionally homogenous, or are they viscerotopically organized with respect to particular end organs? (ii) What are their afferent inputs? (iii) What are their histochemical properties? Specifically, are they part of the group of adrenaline-synthesizing cells, or alternatively, substance P cells?


Comparison of magnetic resonance imaging and computed tomography in suspected lesions in the posterior cranial fossa.
To compare computed tomography and magnetic resonance imaging in investigating patients suspected of having a lesion in the posterior cranial fossa. Randomised allocation of newly referred patients to undergo either computed tomography or magnetic resonance imaging; the alternative investigation was performed subsequently only in response to a request from the referring doctor. A regional neuroscience centre serving 2.7 million. 1020 Patients recruited between April 1986 and December 1987, all suspected by neurologists, neurosurgeons, or other specialists of having a lesion in the posterior fossa and referred for neuroradiology. The groups allocated to undergo computed tomography or magnetic resonance imaging were well matched in distributions of age, sex, specialty of referring doctor, investigation as an inpatient or an outpatient, suspected site of lesion, and presumed disease process; the referring doctor's confidence in the initial clinical diagnosis was also similar. After the patients had been imaged by either computed tomography or magnetic resonance (using a resistive magnet of 0.15 T) doctors were given the radiologist's report and a form asking if they considered that imaging with the alternative technique was necessary and, if so, why; it also asked for their current diagnoses and their confidence in them. Number of requests for the alternative method of investigation. Assessment of characteristics of patients for whom further imaging was requested and lesions that were suspected initially and how the results of the second imaging affected clinicians' and radiologists' opinions. Ninety three of the 501 patients who initially underwent computed tomography were referred subsequently for magnetic resonance imaging whereas only 28 of the 493 patients who initially underwent magnetic resonance imaging were referred subsequently for computed tomography. Over the study the number of patients referred for magnetic resonance imaging after computed tomography increased but requests for computed tomography after magnetic resonance imaging decreased. The reason that clinicians gave most commonly for requesting further imaging by magnetic resonance was that the results of the initial computed tomography failed to exclude their suspected diagnosis (64 patients). This was less common in patients investigated initially by magnetic resonance imaging (eight patients). Management of 28 patients (6%) imaged initially with computed tomography and 12 patients (2%) imaged initially with magnetic resonance was changed on the basis of the results of the alternative imaging. Magnetic resonance imaging provided doctors with the information required to manage patients suspected of having a lesion in the posterior fossa more commonly than computed tomography, but computed tomography alone was satisfactory in 80% of cases...


A randomized, double-blind, placebo-controlled trial of modafinil for negative symptoms in schizophrenia.
Negative symptoms are core features of schizophrenia that are functionally debilitating, associated with poor outcomes, and resistant to existing pharmacotherapies. We performed a randomized, double-blind, placebo-controlled study of modafinil, a medication approved for the treatment of excessive daytime sleepiness, to explore its efficacy as an adjunctive therapy for negative symptoms in schizophrenia. Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned to double-blind treatment with modafinil or placebo for 8 weeks. The study ran from March 2002 through March 2006. Outcome measures included the Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI) scale, Quality of Life Interview, neurocognitive assessments (California Verbal Learning Test, Degraded Performance-Continuous Performance Test, Trail-Making Test B), and somatic measures (sleep, weight, side effects). Modafinil treatment was associated with a greater rate (CGI-Improvement [CGI-I] score < or = 3, 7/10 vs. 1/10) and degree (mean CGI-I score, 3.2 vs. 4.1) of global improvement at study endpoint compared with placebo. However, modafinil did not significantly improve global negative symptoms as measured by the total SANS or SANS individual global items. Modafinil did not significantly worsen psycho-pathology (according to the BPRS), compared with placebo, and was well tolerated. Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms.


6-month clinical outcomes following implantation of the bioresorbable everolimus-eluting vascular scaffold in vessels smaller or larger than 2.5 mm.
We investigated the 6-month clinical outcomes after implantation of second-generation 3.0-mm bioresorbable everolimus-eluting vascular scaffolds (BVS) in small coronary vessels (<2.5 mm). BVS are a novel approach to treating coronary lesions and are untested in small vessels. The ABSORB Cohort B Trial is a multicenter, single-arm, prospective, open-label trial assessing the performance of the second-generation BVS, in which 101 patients were enrolled. The pre-procedural reference vessel diameter (RVD) was assessed by quantitative coronary angiography during post hoc analysis. The vessel size was overestimated, by visual assessment, in 41 patients before implantation of 3.0-mm BVS in vessels with a pre-procedural RVD <2.5 mm. The study population was divided into 2 groups, group I (n = 41) with RVD <2.5 mm and group II (n = 60) with RVD ≥2.5 mm. The composite endpoint of ischemia-driven major adverse cardiac events, defined as ischemia-driven target lesion revascularization, myocardial infarction, or cardiac death, was assessed. Of the 45 patients scheduled for 6-month coronary angiography, 42 patients had the procedure performed, with intravascular ultrasound undertaken in 40 of these patients. At 6 months, no significant differences in ischemia-driven major adverse cardiac events (3 of 41 [7.3%] cases vs. 2 of 60 [3.3%] cases; p = 0.3933) were observed in the small- and large-vessel groups, respectively. No cardiac deaths or episodes of in-scaffold thromboses were seen. Angiographic and intravascular ultrasound follow-up demonstrated no differences in late lumen loss (0.16 ± 0.18 mm vs. 0.21 ± 0.17 mm; p = 0.3525) or percentage lumen area stenosis (17.6 ± 6.0% vs. 19.8 ± 8.5%; p = 0.3643). The second-generation 3.0-mm BVS appears to be safe in small vessels, with similar clinical and angiographic outcomes compared with those of large vessels.