[Research progress and future development prospect of transanal total mesorectal excision].
Transanal total mesorectal excision (taTME) is one of the hotspots in colorectal surgery in recent years. Although most studies confirm that taTME is safe and feasible, some studies still showed that the morbidity of complication and local recurrence rate of taTME were higher than traditional laparoscopic surgery. This article reviews and analyzes the short-term and long-term outcomes of taTME and the related progress of postoperative function. The results showed that there were no significant differences in the main short-term and long-term efficacy between taTME and traditional laparoscopic TME, but taTME had potential advantages in postoperative functional recovery. The results of case study after passing the learning curve suggested that taTME had better short-term and long-term efficacy. Moreover, with the maturity of taTME technology, transanal endoscopic surgery has gradually shown its advantages in the treatment of complex pelvic diseases. In the future, the application of single-port robot will further promote the development of natural orifice transluminal endoscopic colorectal surgery.


Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43.
In multiple sclerosis (MS), glial cells astrocytes interact with the autoreactive immune cells that attack the central nervous system (CNS), which causes and sustains neuroinflammation. However, little is known about the direct interaction between these cells when they are in close proximity in the inflamed CNS. By using an experimental autoimmune encephalomyelitis (EAE) model of MS, we previously found that in the proximity of autoreactive CNS-infiltrated immune cells (CNS-IICs), astrocytes respond with a rapid calcium increase that is mediated by the autocrine P2X7 receptor (P2X7R) activation. We now reveal that the mechanisms regulating this direct interaction of astrocytes and CNS-IICs involve the coupling between P2X7R, connexin-43, and β3-integrin. We found that P2X7R and astroglial connexin-43 interact and concentrate in the immediate proximity of the CNS-IICs in EAE. P2X7R also interacts with β3-integrin, and the block of astroglial αvβ3-integrin reduces the P2X7R-dependent calcium response of astrocytes upon encountering CNS-IICs. This interaction was dependent on astroglial mitochondrial activity, which regulated the ATP-driven P2X7R activation and facilitated the termination of the astrocytic calcium response evoked by CNS-IICs. By further defining the interactions between the CNS and the immune system, our findings provide a novel perspective toward expanding integrin-targeting therapeutic approaches for MS treatment by controlling the cell-cell interactions between astrocytes and CNS-IICs.


Impartiality, statistical tit-for-tats and the construction of balance: UK television news reporting of the 2016 EU referendum campaign.
There has been greater news industry recognition in recent years that impartiality should not be translated into simply balancing the competing sides of a debate or issue. The binary nature of a referendum campaign represents a unique moment to consider whether broadcasters have put this into practice beyond routine political reporting. This study examines how impartiality was editorially interpreted in television news coverage during the United Kingdom's 2016 European Union referendum. We carried out a systematic content analysis of the United Kingdom's main evening bulletins over the 10-week campaign, examining the issues and sources shaping coverage, as well as all the statistical claims made by campaign actors. Our aim was to critically examine how notions of impartiality were constructed and interpreted, exploring any operational limits and political consequences. Overall, we found that news bulletins maintained a fairly strict adherence to a central binary balance between issues and actors during the campaign. But this binary was politically inflected, with a significant imbalance in party political perspectives, presenting us with a right-wing rather than a left-wing case for European Union membership. We also found that independent expert analysis and testimony was sucked into the partisan binary between leave and remain campaigners, while journalists were reluctant to challenge or contextualise claims and counter-claims. Journalists were, in this sense, constrained by the operational definition of impartiality adopted by broadcasters. We argue for a more evidence-driven approach to impartiality, where journalists independently explore the veracity of campaign claims and have the editorial freedom to challenge them. We also suggest that the reliance on claims and counter-claims by leading Conservative politicians did little to advance public understanding of the European Union, and helped perpetuate a series of long-standing negative associations the British media have been reporting for many decades.


Lurcher mice exhibit potentiation of GABA(A)-receptor-mediated conductance in cerebellar nuclei neurons in close temporal relationship to Purkinje cell death.
In heterozygous Lurcher mice (Lc/+), the Purkinje cells (PCs) degenerate almost totally during postnatal development. On the other hand, their projection target, the deep cerebellar nuclei (DCN), shows few signs of degeneration and seems to play an important role in maintaining a residual cerebellar function in Lc/+. We asked whether the DCN in Lc/+ develop cellular adaptations allowing them to cope with the loss of GABAergic PC input. Using whole-cell patch-clamp recordings, we measured inhibitory postsynaptic currents from DCN of Lc/+ and wild-type mice (WT). In experiments on phenotypically striking Lc/+ studied well after the onset of the PC degeneration, we found enlarged average synaptic conductances (g(syn)) compared with WT. We next investigated postnatal mice before and after the onset of PC death. In younger animals </= postnatal day (p) 13, no difference was found in g(syn) between the two groups. At p14, g(syn) in Lc/+ showed an increase, while those in WT stayed on the level found in younger animals. A peak-scaled nonstationary fluctuation analysis suggests that an increase in the average number of channels open at peak is the basis for the change in g(syn). The changes in g(syn), suitable to increase the efficacy of GABAergic transmission, occur in close temporal relationship to PC death and, thus, may reflect a functional adaptation to the loss of the DCN's main GABAergic afferents.


Usnic Acid-Loaded Magnetite Nanoparticles-A Comparative Study between Synthesis Methods.
Since cancer is a continuously increasing concern for the general population, more efficient treatment alternatives ought to be developed. In this regard, a promising direction is represented by the use of magnetite nanoparticles (MNPs) to act both as a nanocarrier for the targeted release of antitumoral drugs and as hyperthermia agents. Thus, the present study focused on improving the control upon the outcome properties of MNPs by using two synthesis methods, namely the co-precipitation and microwave-assisted hydrothermal method, for the incorporation of usnic acid (UA), a natural lichen-derived metabolite with proven anticancer activity. The obtained UA-loaded MNPs were thoroughly characterized regarding their morpho-structural and physicochemical properties through X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and zeta potential, scanning electron microscopy (SEM), and vibrating sample magnetometry (VSM). Results demonstrated the formation of magnetite as the unique mineralogical phase through both types of synthesis, with increased uniformity regarding the drug loading efficiency, size, stability, and magnetic properties obtained through the microwave-assisted hydrothermal method. Furthermore, the cytotoxicity of the nanostructures against the HEK 293T cell line was investigated through the XTT assay, which further proved their potential for anticancer treatment applications.


Quantifying proportional variability.
Real quantities can undergo such a wide variety of dynamics that the mean is often a meaningless reference point for measuring variability. Despite their widespread application, techniques like the Coefficient of Variation are not truly proportional and exhibit pathological properties. The non-parametric measure Proportional Variability (PV) [1] resolves these issues and provides a robust way to summarize and compare variation in quantities exhibiting diverse dynamical behaviour. Instead of being based on deviation from an average value, variation is simply quantified by comparing the numbers to each other, requiring no assumptions about central tendency or underlying statistical distributions. While PV has been introduced before and has already been applied in various contexts to population dynamics, here we present a deeper analysis of this new measure, derive analytical expressions for the PV of several general distributions and present new comparisons with the Coefficient of Variation, demonstrating cases in which PV is the more favorable measure. We show that PV provides an easily interpretable approach for measuring and comparing variation that can be generally applied throughout the sciences, from contexts ranging from stock market stability to climate variation.


[Combined drug sensitivity test of 50 strains of extensively drug-resistant Acinetobacter baumannii].
To study the in vitro antibacterial activity of meropenem combined with doxycycline, ciprofloxacin, sulbactam or cefoperazone/sulbactam against clinically isolated extensively drug-resistant Acinetobacter baumannii (XDRAB). Using a checker board synergy design, the minimal inhibitory concentration (MIC) of antibiotics against 50 isolates of XDRAB was determined by broth microdilution antifungal susceptibility test. The fractional inhibitory concentration (FIC) index was calculated to determine the combined effect of the antibiotics. Meropenem showed significantly reduced MIC50 and enhanced antimicrobial activities when combined with doxycycline, sulbactam or cefoperazone/sulbactam. The FIC results suggested that the main actions of doxycycline, sulbactam, and cefoperazone/sulbactam were synergistic (38%, 26%, and 10%, respectively) and addictive (62%, 74%, and 90%, respectively) without indifferent or antagonistic effects. The main actions of meropenem combined with ciprofloxacin were additive (56%) and indifference (44%) with synergistic and antagonistic effects. Meropenem combined with doxycycline, sulbactam or cefoperazone/sulbactam shows excellent activity against clinical isolates of XDRAB.


Vulnerability to stress: self-criticism and stress-induced changes in biochemistry.
It has been hypothesized that individuals who are high on the attribute of self-criticism are particularly vulnerable to failure stress. To test this hypothesis, we examined the relationship between self-criticism and changes in plasma homovanillic acid (HVA; the metabolite of dopamine) and emotion during exposure to an induced-failure task. Participants consisted of 21 women. Plasma HVA and emotion were assessed at three time points: baseline (T1), during stress exposure (T2), and 40 minutes after cessation of the stressor (T3). We found that self-criticism was significantly and positively related to changes in plasma HVA during stress exposure. In addition, the personality attribute was significantly and positively related to subjective ratings of stress and changes in scores on the Confusion-Bewilderment scale of the Profile of Mood States during the task. To our knowledge, this is the first study to report that self-criticism is related to stress-induced changes in biochemistry.


Usability testing for the rest of us: the application of discount usability principles in the development of an online communications assessment application.
Usability evaluation provides developers and educators with the means to understand user needs, improve overall product utility, and increase user satisfaction. The application of "discount usability" principles developed to make usability testing more practical and useful may improve user experience at minimal cost and require little existing expertise to conduct. We describe an application of discount usability to a high-fidelity online communications assessment application developed by the University of Washington for the American Board of Internal Medicine. Eight internal medicine physicians completed a discount usability test. Sessions were recorded and the videos analyzed for significant usability concerns. Concerns were identified, summarized, discussed, and prioritized by the authors in collaboration with the software developers before implementing any changes to the interface. Thirty-eight significant usability issues were detected and four technical problems were identified. Each issue was responded to through modification of the software, by providing additional instruction, or delayed for a later version to be developed. Discount usability can be easily implemented in academic developmental activities. Our study resulted in the discovery and remediation of significant user problems, in addition to giving important insight into the novel methods built into the application.


Nivolumab in renal cell carcinoma: latest evidence and clinical potential.
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses. The strategy of immune checkpoint blockade is to reduce inhibitory signaling and restore the patient's natural tumor-specific T-cell-mediated immune responses. Nivolumab is the first PD-1 inhibitor to have gained approval for the treatment of patients with metastatic melanoma, squamous and nonsquamous non-small cell lung cancer (NSCLC), Hodgkin disease and recently RCC. In this review, we discuss results from studies of nivolumab in RCC, clinical experience with this agent, and its future development.


Biomimetic Optical Cellulose Nanocrystal Films with Controllable Iridescent Color and Environmental Stimuli-Responsive Chromism.
As a wise and profound teacher, nature provides numerous creatures with rich colors to us. To biomimic structural colors in nature as well as color changes responsive to environmental stimuli, there is a long way to go for the development of free-standing photonic films from natural polymers. Herein, a highly flexible, controllably iridescent, and multistimuli-responsive cellulose nanocrystal (CNC) film is prepared by simply introducing a small molecule as both plasticizer and hygroscopic agent. The presence of the additive does not block the self-assembly of CNC in aqueous solution but results in the enhancement of its mechanical toughness, making it possible to obtain free-standing iridescent CNC films with tunable structural colors. In response to environmental humidity and mechanical compression, such films can change structural colors smoothly by modulating their chiral nematic structures. Notably, the chromism is reversible by alternately changing relative humidity between 16 and 98%, mimicking the longhorn beetle Tmesisternus isabellae. This chromic effect enables various applications of the biofilms in colorimetric sensors, anticounterfeiting technology, and decorative coatings.


Ectopic fat accumulation and metabolic syndrome.
The recent escalation of obesity from an individual health problem to a major public health issue reaching epidemic proportions has drawn attention to a constellation of abnormalities (abdominal obesity, hypertension and dyslipidaemia) collectively referred to as metabolic syndrome. As an indicator of insulin resistance and a harbinger of diabetes, this syndrome has been associated with major cardiovascular mortality and morbidity. Yet, the exact pathophysiological events leading to the development of metabolic syndrome remain unknown. We review some of the current literature on the pathogenesis of metabolic syndrome with an emphasis on the role of ectopic lipid accumulation.


Targeted approaches to delineate neuronal morphology during early development.
Understanding the developmental changes that affect neurons is a key step in exploring the assembly and maturation of neural circuits in the brain. For decades, researchers have used a number of labeling techniques to visualize neuronal morphology at different stages of development. However, the efficiency and accuracy of neuronal labeling technologies are limited by the complexity and fragility of neonatal brains. In this review, we illustrate the various labeling techniques utilized for examining the neurogenesis and morphological changes occurring during the early stages of development. We compare the advantages and limitations of each technique from different aspects. Then, we highlight the gaps remaining in our understanding of the structure of neurons in the neonatal mouse brain.


The effect of body mass index on internal rotation and function following anatomic and reverse total shoulder arthroplasty.
The exact relationship between body mass index (BMI) and internal rotation (IR) before and after total shoulder arthroplasty has not been studied to date. The purpose of this study was to determine the effects of BMI on the preoperative and postoperative shoulder range of motion and function in anatomic (aTSA) and reverse total shoulder arthroplasty (rTSA), and specifically how IR affects patient ability to perform IR-related activities of daily living (ADLs). Patients from a prospective multicenter international shoulder arthroplasty registry who underwent primary rTSA (n=1171) and primary aTSA (n=883) were scored preoperatively and at latest follow-up (2-10 years, mean = 3 years) using the Simple Shoulder Test, University of California-Los Angeles shoulder score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Constant score, and Shoulder Pain and Disability Index patient-reported outcome measures (PROMs). Measured active abduction, forward flexion, IR, and active and passive external rotation were recorded, and BMI was evaluated as a predictor of motion and patient-reported outcomes. Patient responses to questions regarding the difficulty level of IR-related ADLs were studied. The relationships between BMI, IR, and ability to perform IR-related ADLs were quantified through analysis of variance with post hoc comparisons by Tukey honestly significant difference tests, where significance was denoted as P < .05. BMI was found to be inversely correlated with IR in patients undergoing both aTSA and rTSA, both preoperatively (P < .001 and P = .002) and postoperatively (P < .001 and P < .001). BMI affected the range of motion parameters of forward flexion abduction and external rotation but to a lesser extent than that of IR. Nonobese patients demonstrated significantly greater IR than overweight, obese, and morbidly obese patients postoperatively for aTSA (P < .001). For rTSA, nonobese patients had a significantly greater postoperative IR than obese and morbidly obese patients (P < .001 and P = .011, respectively). For both aTSA and rTSA patients, mean IR scores significantly differed between patients reporting normal function vs. patients reporting slight difficulty, considerable difficulty, or inability to perform IR-related ADLs. Increasing IR demonstrated a significant, positive correlation with all PROMs for both aTSA and rTSA patients (Pearson correlation, P < .001). BMI is an independent predictor of IR, even when controlling for age, gender, glenosphere size, and subscapularis repair. BMI was inversely correlated with the degree of IR, and decreased IR significantly negatively affected the ability to perform IR-related ADLs. Increasing BMI adversely affects shoulder ROM, particularly IR. IR is correlated with the ability to perform ADLs requiring IR in both aTSA and rTSA patients.


Association of calf circumference with insulin resistance and non-alcohol fatty liver disease: the REACTION study.
The feature of nonalcoholic fatty liver disease (NAFLD) is pathological excessive liver lipid accumulation of subjects who without history of alcohol abuse. Calf circumference is a proxy for lower-body fat and screening method for the identification of subjects with acatastatic lipid accumulation. The objective of this study was to examine the association between calf circumference and NAFLD. The study was a cross-sectional analysis including 8850 middle-aged and elderly individuals. NAFLD was examined by hepatic ultrasound and without alcohol abuse and other liver diseases. Calf circumference was measured on the lower right leg at the point of maximal circumference. The mean of calf circumference were 35.7 cm for male and 34.6 cm for female (P < 0.001), respectively. Compared with the lowest calf circumference quartile, the odds ratio for NAFLD in the highest quartile was 2.73 (95% CI 2.34-3.19, P trend <0.001) after adjusted for potential cofounders. There were also significant positive correlation between calf circumference and HOMA-IR, liver enzyme levels and triglycerides. In addition, we found significant positive correlation of calf circumference with the HOMA-IR and fasting insulin level in overweight and obese subjects (BMI ≥ 24 kg/m2) but not in lean subjects (test for interaction: P both less than 0.001 for insulin and HOMA-IR). High calf circumference is significantly associated with elevated prevalence of NAFLD and increasing insulin resistance.


Retinal Structure in RPE65-Associated Retinal Dystrophy.
RPE65-associated retinal dystrophy (RPE65-RD) is an early onset, progressive, severe retinal dystrophy. We sought to characterize the natural history of retinal degeneration in affected individuals. We performed cross-sectional and longitudinal quantitative and qualitative assessments of retinal architecture in RPE65-RD using spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging. Twenty-six subjects (mean age, 14.8 years, range, 5-24 years) with RPE65-RD underwent SD-OCT and FAF imaging, of whom 14 subjects were followed up over time. Foveal thickness (FT), outer nuclear layer thickness (ONLT), ellipsoid zone width (EZW), and ellipsoid zone area (EZA) were calculated where possible. These were correlated with age, best corrected visual acuity (BCVA), and central 30° retinal sensitivity (V30). Intra-observer agreement, test-retest repeatability, and interocular symmetry were also investigated. We identified structural interocular symmetry, the presence of autofluorescence in 46% (12/26) of subjects, and the presence of foveal hypoplasia (associated with significantly worse BCVA) in 50% of subjects. EZW and EZA were measurable in 67% (35/52) and 37% (19/52) of eyes, respectively, with both demonstrating good agreement on repeated measurement. The annual rate of progression using EZW was -300.63 µm/year, and -1.17 mm2/year in EZA. EZW was found to have a statistically significant correlation with BCVA and V30. We identified the presence of autofluorescence in half of our subjects, with foveal hypoplasia also noted in half of our cohort. EZW, and to a lesser extent EZA, were robust measures of retinal degeneration and represent valuable metrics to determine the impact of intervention. (ClinicalTrials.gov number NCT02714816.).


Hippocampus contributes to the maintenance but not the quality of visual information over time.
The hippocampus has recently been implicated in the brief representation of visual information, but its specific role is not well understood. We investigated this role using a paradigm that distinguishes quantity and quality of visual memory as described in a previous study. We found that amnesic patients with bilateral hippocampal damage (N = 5) were less likely to remember test stimuli than comparison participants despite a brief maintenance interval (900 msec). However, estimates of memory quality were similar for all groups. Our findings suggest that the hippocampus contributes to brief maintenance of visual information but does not contribute to the quality of that information.


Distraction Gap Needed for Safe Central Compartment Access in Hip Arthroscopy.
Sufficient distraction of the hip is the key to a safe central compartment (CC) approach in hip arthroscopy. However, an adequate distraction gap has not been scientifically identified. To determine the sufficient amount of distraction that could predict a successful CC access as well as to identify the risk factors for a failed or difficult CC access. Case-control study; Level of evidence, 3. All patients who underwent hip arthroscopy by a single surgeon between January 2018 and April 2019 were prospectively enrolled. We analyzed gaps of the hip on 4 C-arm fluoroscopic images: nondistraction, preoperative manual traction, preoperative maximal traction (without distension), and intraoperative maximal traction (at the end of CC procedures in a successful CC approach or after peripheral compartment procedures in a failed or difficult CC approach). A failed CC approach was defined as failure in introducing the anterolateral portal to the CC under arthroscopic control; a difficult CC approach was defined as the presence of an incomplete diagnostic round in the CC because of a small distraction. The amount of distraction was evaluated by the ratio of the distracted gap to the undistracted gap. Patients were classified into the successful CC access group (group 1) and the failed/difficult CC access group (group 2). The amount of distraction, demographic characteristics, and preoperative radiographic parameters were compared between the groups. A total of 240 patients were included in this study. Group 1 consisted of 205 patients (113 males and 92 females; mean ± SD age, 34.5 ± 11.4 years), and group 2 consisted of 35 patients (27 males and 8 females; age, 32.5 ± 11.2 years). The preoperative joint space width was not significantly different between group 1 (mean ± SD, 3.89 ± 0.83 mm) and group 2 (3.68 ± 0.68 mm). The ratio of the amount of distraction at lateral gaps under all traction conditions was significantly greater in group 1 compared with group 2 (1.50 ± 0.54 vs 1.26 ± 0.35, respectively, under preoperative manual traction; 2.84 ± 0.76 vs 2.03 ± 0.63 under preoperative maximal traction; 3.36 ± 0.96 vs 2.50 ± 0.79 under intraoperative maximal traction). An increase of the lateral gap by >2.2 times (P < .001) under preoperative maximal traction and by >2.7 times (P < .001) under intraoperative maximal traction could predict successful CC access. Male sex (odds ratio [OR], 2.94; P = .017) and increased lateral center-edge angle (OR, 1.08 for every 1° increase; P = .004) were significant risk factors for failed/difficult CC access. An increase of the lateral gap by >2.2 times during an unsterile traction test without joint distension could predict successful CC access. Male sex and increased lateral center-edge angle were risk factors for a failed or difficult CC access.


Imaging of the optic nerve and retinal nerve fiber layer: an essential part of glaucoma diagnosis and monitoring.
Because glaucomatous damage is irreversible early detection of structural changes in the optic nerve head and retinal nerve fiber layer is imperative for timely diagnosis of glaucoma and monitoring of its progression. Significant improvements in ocular imaging have been made in recent years. Imaging techniques such as optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy rely on different properties of light to provide objective structural assessment of the optic nerve head, retinal nerve fiber layer and macula. In this review, we discuss the capabilities of these imaging modalities pertinent for diagnosis of glaucoma and detection of progressive glaucomatous damage and provide a review of the current knowledge on the clinical performance of these technologies.


Inhaled nitric oxide at the time of harvest improves early lung allograft function.
Inhalation of nitric oxide (NO) has been shown to have beneficial effects on a variety of acute lung injuries, including lung allograft reperfusion injury. The purpose of the present study was to investigate the effects of inhaled NO at the time of harvest on function of canine left lung allografts after transplantation. Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gases (inspired oxygen fraction, 1.0) were assessed intermittently for 6 hours prior to sacrifice. Allograft myeloperoxidase activity and wet to dry weight ratio were assessed. Donor animals were divided into two groups. Group I animals (n = 5) received no NO. In group II (n = 5), donors received inhaled NO (60 ppm) at the time of harvest. Pulmonary vascular resistance decreased to 79.6% of baseline because of inhalation of 60 ppm NO in group II donor animals. Thiobarbituric acid-reactive materials were reduced during the storage period in group II, a finding suggesting less oxidant injury during storage in donor lungs treated with NO. Throughout the 6-hour assessment, oxygenation in group II was superior to that in group I (p < 0.05). At 360 minutes of assessment, mean arterial oxygen tension in groups I and II was 88.9 +/- 11.4 mm Hg and 169.1 +/- 33.0 mm Hg, respectively. Myeloperoxidase activity was significantly decreased in group II (p < 0.05), data indicating reduced neutrophil sequestration. Wet to dry weight ratio was significantly lower in group II. These data suggest that inhaled NO at the time of harvest improves early function of preserved lung allografts by attenuating oxidant injury during storage and subsequent neutrophil sequestration.


Candidemia from an upper urinary tract infection complicated by candida endophthalmitis.
A 51-year-old Japanese woman developed candidemia as an outpatient secondary to a Candida albicans upper urinary tract infection complicated by previously undiagnosed type 2 diabetes mellitus with poor glycemic control and ureterolithiasis. The patient did not have any risk factors typically associated with candidemia, such as an indwelling vascular catheter, parenteral nutrition or broad-spectrum antibiotic use. During the clinical course, her condition was complicated by unilateral candida endophthalmitis, which progressed despite the administration of systemic antifungal agents and ultimately required vitreous surgery. The etiology of candidemia in this patient and the reason she developed progressive ocular symptoms after starting antifungal treatment are reviewed.


Prevention of relapse following cognitive therapy vs medications in moderate to severe depression.
Antidepressant medication prevents the return of depressive symptoms, but only as long as treatment is continued. To determine whether cognitive therapy (CT) has an enduring effect and to compare this effect against the effect produced by continued antidepressant medication. Patients who responded to CT in a randomized controlled trial were withdrawn from treatment and compared during a 12-month period with medication responders who had been randomly assigned to either continuation medication or placebo withdrawal. Patients who survived the continuation phase without relapse were withdrawn from all treatment and observed across a subsequent 12-month naturalistic follow-up. Outpatient clinics at the University of Pennsylvania and Vanderbilt University. A total of 104 patients responded to treatment (57.8% of those initially assigned) and were enrolled in the subsequent continuation phase; patients were initially selected to represent those with moderate to severe depression. Patients withdrawn from CT were allowed no more than 3 booster sessions during continuation; patients assigned to continuation medication were kept at full dosage levels. Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression or Hamilton Depression Rating Scale scores of 14 or higher during the continuation phase. Recurrence was defined in a comparable fashion during the subsequent naturalistic follow-up. Patients withdrawn from CT were significantly less likely to relapse during continuation than patients withdrawn from medications (30.8% vs 76.2%; P = .004), and no more likely to relapse than patients who kept taking continuation medication (30.8% vs 47.2%; P = .20). There were also indications that the effect of CT extends to the prevention of recurrence. Cognitive therapy has an enduring effect that extends beyond the end of treatment. It seems to be as effective as keeping patients on medication.


Alpha-thalassemia in Saudi Arabia: deletion pattern.
Alpha-Thalassemia exists at a high prevalence in several regions of Saudi Arabia. The restriction endonucleases BamHI and BglII were used to investigate the molecular basis of deletion type of alpha-thalassemia in 226 subjects from the eastern and 61 subjects from the northwestern regions of the country. The arrangements -alpha/alpha alpha and -alpha/-alpha were common. BglII digestion revealed the existence of rightward deletion in a majority of the cases. Leftward deletions, both homozygous and heterozygous, were also identified. Triple alpha-gene arrangements alpha alpha alpha anti 3.7/ were observed at a low frequency in both regions.


Augmentation of Helicobacter pylori urease activity by its specific IgG antibody: implications for bacterial colonization enhancement.
Gastric colonization of Helicobacter pylori (H. pylori) occurs in a very early age via infected mothers having H. pylori-specific IgG antibodies that would be transplacentally transferred to infants. In addition, H. pylori urease-specific IgG was associated with chronic gastric atrophy and post-immunization gastritis is usually correlated with a strong local IgG response. These findings indicate that H. pylori-specific IgG antibodies, in particular its urease-specific IgG, may induce unfavorable influence on host resistance against H. pylori. Here, we show that we have found a unique H. pylori urease-specific IgG monoclonal antibody (MAb), termed S3, recognizing the conformational structure of the small subunit Ure-A, which enhanced the urease enzymatic activity. Such enhancement of the H. pylori urease activity induced by 1 microg of S3 was almost completely cancelled by simultaneously added the same amount of L2 MAb, which has a strong and specific inhibitory activity against H. pylori urease and recognizes a liner epitope of 8-mer peptide (F8: SIKEDVQF) within its large subunit Ure-B (Infect. Immun. 69: 6597, 2001). Intravenous pre-administration of purified S3 into BALB/c mice showed significant augmentation for gastric colonization with the susceptible strain Sydney Strain-1 (SS-1). To our knowledge, this is the first demonstration that a H. pylori urease-specific IgG MAb induced an augmentation of their gastric colonization in vivo.


Cerebriform giant melanocytic nevus of the scalp: report of two cases with different surgical approaches.
Cerebriform giant melanocytic nevus of the scalp is an extremely rare malformation. Clinical appearance with maceration and fetor within the crypts and the risk of malignant transformation may require surgical therapy. We report two cases with different methods of surgical management. A 27-year-old woman noticed a swelling of the parietal scalp that developed over a period of 4 years into a gyrus-like tumor measuring 12 cm x 18 cm. The crypts between the gyri could not be inspected. Serial excisions under subcutaneous infusion anesthesia were performed to reduce the size of the nevus and to flatten the surface of the scalp. The second patient, a 26-year-old man, demonstrated a giant 10 cm x 10 cm cerebriform nevus on the occiput. The nevus also contained areas of fetid maceration. After implanting a tissue expander under general anesthesia the nevus was excised. The defect was closed using a rotation flap.


Increase in relapse rate during assisted reproduction technique in patients with multiple sclerosis.
The objective was to determine if there is an increased risk to develop exacerbations in patients with multiple sclerosis (MS) after assisted reproduction technique (ART). An increase in annual relapse rate (ARR) was described after ART in a small cohort of patients. We investigated the associations between ART and relapse rate (RR) in 23 MS patients who underwent 78 hormonal stimulations in total. There was a statistically significant increase in the RR following ART independent of the hormonal approach or the time interval between the stimulations. These results suggest that female MS patients who wish to have children should be informed that the RR may be increasing if ART is necessary.


[Urinary tests for inflammation in glomerulonephritis].
Boyden camera tests, chemiluminescence of urinary supernatant, passive hemagglutination tests were used in measuring chemotactic properties of the urine, intensity of free-radical processes, fibronectin urine concentrations, respectively, in 31 glomerulonephritis (GN) patients. The above parameters were closely related to nephritis activity. These were much lower in patients with nephritis remission, than in subjects with nephrotic syndrome or exacerbation of latent nephritis. Chemotactic activity and intensity of free-radical processes were unrelated to protein urea which, however, correlated with fibronectin concentrations (r = 0.35, p < 0.05). The authors discuss the role of the mediators' values in evaluation of local renal inflammation and feasibility of their use as criteria of nephritis activity and prognosis.


Analyzing the research record of an institution's list of faculty publications.
Few health sciences libraries maintain databases and produce bibliographies of the publications of their institution's faculty. By offering such services, libraries can provide faculty members with a qualitative analysis of where and how their research is cited and its impact in the fields of biomedicine and related health sciences. Journal Citation Reports (JCR), produced by the Institute for Scientific Information, is a powerful tool that provides information on citations appearing in the largest, most frequently used, most cited, and highest-impact journals. This paper discusses the role libraries play in providing information about faculty publications, reviews how JCR is used by libraries, discusses how the Ehrman Medical Library of the New York University Medical Center uses JCR, and makes recommendations for the use of JCR to strengthen the librarian's role in providing information to faculty about the value of their research.


Morphine formation from ethylmorphine: implications for drugs-of-abuse testing in urine.
In drugs-of-abuse testing, opiates constitute a delicate and controversial task because morphine may occur in urine for several reasons. Ethylmorphine (EtM), which is used as an antitussive drug in many countries, is metabolically converted to morphine. The present study was performed in order to document intra- and interindividual differences in morphine formation after single-dose intake of EtM at two different doses (25 and 50 mg). The urinary excretion of opiates was measured during 48 h with EMIT and gas chromatography-mass spectrometry in 10 healthy volunteers. The mean values of totally recovered EtM and morphine in hydrolyzed urine during 48 h were 42 and 47% of the given dose at high and low dose level, respectively. The ratio between total recovered morphine and EtM ranged from 19 to 131% with a mean value of 48%. The rate of positive outcome in the EMIT opiate-screening assay was 100% during the first 24 h for both doses, and it was still high (> or = 67%) in the 24-48 h time interval. It was found that the decline in urinary EtM is more rapid than for morphine, which leads to an increasing morphine/EtM ratio in urine over time. THe mean value of the morphine/EtM ratio was found to be greater than 1 during the 12-24 h interval and finally increased to greater than 10. There was an intra-individual concordance in morphine/EtM ratio between doses, but there was marked interindividual variation. Morphine/EtM ratios that were greater than 1 were only seen when the concentration of morphine was below 300 micrograms/mmol creatinine. Our results demonstrate that morphine is formed from EtM at a high and variable rate and may be present in urine in concentrations greater than those of EtM even shortly after drug intake.


Vascular permeability in diabetics and implications for therapy.
Several factors contribute to increased vascular permeability in diabetes mellitus, namely hyperglycaemia leading to increased production of diacylglycerol and thence protein kinase C, non-enzymatic glucosylation generating free radicals and lipid peroxides, sorbitol formation, loss of endothelial cell surface heparan sulphates, and the action of arachidonate derivatives that affect endothelial cell contractility. In view of the importance of oxidative damage, serious consideration must be given to therapeutic regimens that utilise vitamin E or ascorbic acid or D-myoinositol. Probucol is an available antioxidant whose properties have received insufficient attention. The oleate of monounsaturated oil diets is likewise anti-oxidant. Furthermore there is a possibility of replacing lost surface heparan sulphates.


Evaluation of immunomagnetic separation and PCR for the detection of Escherichia coli O157 in animal feces and meats.
Series of animal feces and meat samples artificially contaminated with strains of Escherichia coli O157 isolated from different sources were tested by both an immunomagnetic separation (IMS)-based method and a PCR method using primers specific for a portion of the rfbE gene of E. coli O157. IMS is laborious and time consuming but ends up with the isolation of the pathogen. PCR is fast and less laborious, but it can only be used for screening purposes, so a further culture step is required to isolate the organism. For both fecal and meat samples, the IMS method was found to be more sensitive than the PCR. Furthermore, the detection efficiency of the PCR was influenced by the origin of the fecal sample and the type of meat. For sheep feces, the efficiency of the PCR appeared to be systematically lower than for cattle feces. And the efficiency of the PCR in detecting E. coli O157 in spiked samples of raw minced beef and dry-fermented sausages was systematically lower than in samples of filet americain. Based on this study, it can be concluded that both for animal feces and meat, IMS can be used more successfully to detect E. coli O157 than PCR, because IMS showed to be more sensitive and the outcome was not influenced by the type of animal feces or meat.


Clinical outcomes after revision surgery for medial patellofemoral ligament reconstruction.
Medial patellofemoral ligament reconstruction (MPFL-R) is the standard surgical intervention for patella instability. However, limited knowledge exists concerning the causes for failure, and outcome after revision MPFL-R. The purpose of this study is to evaluate the causes of primary MPFL-R failure and clinical outcomes after revision MPFL-R. Twenty-three patients (6 males and 17 females) with failed primary MPFL-R underwent isolated revision MPFL-R or combined revision MPFL-R with tibial tuberosity osteotomy (TTO). The mean age was 23 (SD 8.6). Prior to surgery, dysplasia of the patellofemoral joint, sulcus angle, Insall-Salvati index, cartilage lesions, tibial tuberosity trochlear groove (TTTG) distance, and tunnel placement were evaluated by magnetic resonance imaging (MRI). Their scores on the Kujala Anterior Knee Pain Scale and pain scores were assessed prior to surgery, 1 year post-operatively and at final follow-up. The mean follow-up time was 44 months (median range 39). The radiographic characteristics and clinical outcomes were compared with a 224 primary MPFL-R patient cohort (240 knees). Non-anatomical fixation of the graft at the medial femoral condyle after primary MPFL-R was seen in 67% of revision patients with anterior/proximal misplacement in most cases. Severe trochlear dysplasia Dejour types C and D were seen in 36% of the patients compared to 30% of primary MPFL-R patients (NS). The mean Kujala Anterior Knee Pain Scale score at final follow-up was 61.7 (SD 18.8) compared to 80.3 (SD 18) in primary MPFL-R patients (P < 0.01). The mean pain score at rest was 2.3 (SD 2.5) for revision MPFL-R patients compared to 1.7 (SD 2.5) in primary MPFL-R patients (NS) and their mean pain score during activity was 5.0 (SD 3.2) compared to 1.3 (SD 2.2) in primary MPFL patients (P < 0.001). Although revision MPFL-R establishes acceptable patellar stability, the subjective outcomes after revision MPFL-R do not improve significantly, and are poorer than after primary MPFL-R. Non-anatomical graft position can be an important cause of MPFL-R failure. The clinical relevance of this study is that it shows that it may be difficult to improve self-reported outcomes in revision MPFL-R patients. III.


Quality of life assessment of patients undergoing palliative chemotherapy.
Palliative chemotherapy uses systemic antineoplastic agents to treat an incurable malignancy. The results of cancer treatment need to be measured in terms of what physical and psychological limitations it brings to the patient. Therefore, there is a need to evaluate and establish the impact of the disease and its treatment on the patient's quality of life. To evaluate the quality of life of cancer patients undergoing palliative antineoplastic chemotherapy. A cross-sectional study with quali-quantitative unfolding. Three research instruments were applied: sociodemographic and clinical data; European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30); interview script with predefined open questions. The quality of life of the participants was considered good. Fatigue and financial difficulty were the main factors that interfered in daily activities. Three analytical categories emerged from the content analysis of the interviews: communication between the health team and the patient; patient's perception of their health/disease; concerns vs prospects. The evaluation of quality of life for people who are at the end of life needs to balance technological and therapeutic advances, alongside aspects such as the perspective of these patients and the context of their lives.


Measurement of the Thermal Conductivity of Unfrozen and Frozen Food Materials by a Steady State Method with Coaxial Dual-cylinder Apparatus.
Coaxial dual-cylinder apparatus was used to measure the effective thermal conductivity of aqueous solutions of glucose, sucrose, gelatin and egg albumin over a temperature range from -20° to 20°C by the steady state method. The accuracy of the apparatus was confirmed by testing with water and ice. The effective thermal conductivity decreased with an increase in the total solid content in both the frozen and unfrozen states. In the unfrozen state, the effective thermal conductivity was slightly dependent on temperature. In the frozen state, however, the effective thermal conductivity was strongly dependent on temperature; lower temperatures gave higher effective thermal conductivity, reflecting the increase in the ice fration. For the unfrozen samples, the intrinsic thermal conductivity of each solid component was calculated by heat transfer models. All the models tested, series, parallel and Maxwell-Eucken, were equally applicable to describe the heat conduction in the unfrozen state. In the frozen state, however, the strong temperature dependency of the effective thermal conductivity suggests that the effect of the temperature dependency of the ice fraction should be incorporated into theoretical models.


Spatio-Temporal Graph Representation Learning for Fraudster Group Detection.
Motivated by potential financial gain, companies may hire fraudster groups to write fake reviews to either demote competitors or promote their own businesses. Such groups are considerably more successful in misleading customers, as people are more likely to be influenced by the opinion of a large group. To detect such groups, a common model is to represent fraudster groups' static networks, consequently overlooking the longitudinal behavior of a reviewer, thus, the dynamics of coreview relations among reviewers in a group. Hence, these approaches are incapable of excluding outlier reviewers, which are fraudsters intentionally camouflaging themselves in a group and genuine reviewers happen to coreview in fraudster groups. To address this issue, we propose "FGDT", a framework for "fraudster group detection through temporal relations." FGDT first capitalizes on the effectiveness of the HIN-recurrent neural network (RNN) in both reviewers' representation learning while capturing the collaboration between reviewers. The HIN-RNN models the coreview relations of reviewers in a group in a fixed time window of 28 days. We refer to this as spatial relation learning representation to signify the generalizability of this work to other networked scenarios. Then, we use an RNN on the spatial relations to predict the spatio-temporal relations of reviewers in the group. In the third step, a graph convolution network (GCN) refines the reviewers' vector representations using these predicted relations. These refined representations are then used to remove outlier reviewers. The average of the remaining reviewers' representation is then fed to a simple fully connected layer to predict if the group is a fraudster group or not. Exhaustive experiments of FGDT showed a 5% (4%), 12% (5%), and 12% (5%) improvement over three of the most recent approaches on precision, recall, and F1-value over the Yelp (Amazon) dataset, respectively.


Roles of embryonic and adult lymphoid tissue inducer cells in primary and secondary lymphoid tissues.
The nomenclature "embryonic lymphoid tissue inducer (LTi) cell" reflects the fundamental role of the cell in secondary lymphoid tissue organization. In addition, it is equally important in primary lymphoid tissue development as it regulates central tolerance to self-antigens in the thymus. An adult LTi cell constitutively expresses two sets of tumor necrosis factor (TNF) family members, whereas its embryonic counterpart expresses only one. The first set is lymphotoxin (LT)alpha, LTbeta, and TNalpha, which are essential for the secondary lymphoid organogenesis during embryogenesis and for maintaining an organized secondary lymphoid structure during adulthood. The second set is OX40- and CD30-ligands, which are critical for memory T cell generation. Adult LTi cells regulate adaptive immune responses by providing LTbetaR signals to stromal cells to maintain secondary lymphoid tissue structure, and determine adaptive immune responses by providing OX40 and CD30 survival signals to activated T cells in memory T cell generation. Along with the consideration of the roles of embryonic LTi cells in primary and secondary lymphoid tissues, this review highlights the roles of adult LTi cells in secondary lymphoid tissue function.


Can Concomitant Masticatory Muscle Contraction Interfere with Temporomandibular Joint Arthralgia Evaluation?
To investigate the effect of masticatory muscle contraction on the pressure pain threshold (PPT) of the lateral pole of the temporomandibular joint (TMJ) in patients with TMJ arthralgia and in asymptomatic individuals. A total of 72 individuals divided into two groups (group 1: patients with unilateral TMJ arthralgia [n = 36]; group 2: control group, asymptomatic individuals [n = 36]) were compared. The PPT of the lateral pole of the TMJ with and without concomitant masticatory muscle contraction was determined using a digital algometer in both groups. Paired and independent Student t test were used to compare the data within and between groups, respectively. A 5% significance level was used for all tests. Higher TMJ PPT values with concomitant masticatory muscle contraction were found in both groups (P < .001). The amount of increase in PPT with contracted muscles was not significantly different between groups (P = .341), but the TMJ arthralgia group had significantly lower PPT values than the control group regardless of muscle contraction status (P < .001). Concomitant masticatory muscle contraction significantly increased the PPT of the lateral pole of the TMJ in relation to relaxed muscles, regardless of the presence of arthralgia.


Blocked Coronary Artery Due To Coronary Spasm Treated With Stent Insertion: A Sub-Optimal Result?
Myocardial infarction (MI) is an extremely common cause of chest pain. MI can be acute with ST elevation (STEMI) or non-STEMI (NSTEMI). Coronary artery spasm can be severe enough to cause occlusion of the coronary arteries particularly with an exaggerated response in regions of coronary atheroma and plaque ulceration. It is not uncommon for coronary spasm to be mistaken with acute thrombotic occlusion of the coronary artery. We describe a case of a 42-year old man with known cardiac risk factors presents with chest pain for few hours to a tertiary centre hospital. A coronary angiogram showed occlusion of the right epicardial coronary artery with a severe spasm at the level of the atheroma. The initial coronary stent which was deformed because of intense pressure of spasm required another stent to be placed within the first stent. Diltiazem and Nitrates were started as secondary prevention treatment to reduce effect of coronary spasm. The patient made an uneventful recovery and was discharged home with no sequelae over the next 3 years follow up.


A comparison between photon counting histogram and fluorescence intensity distribution analysis.
Photon counting histogram (PCH) and fluorescence intensity distribution analysis (FIDA) are two methods that were developed independently but reported almost simultaneously. Both of them have been successfully applied to fluorescence fluctuation spectroscopy (FFS). Though publications have indicated that they are theoretically equivalent, they are still commonly considered as different methods, especially in their ways to treat the point spread functions (PSFs). In this paper, the two methods are examined in detail for a direct comparison. After a direct proof of the theoretical equivalence, the authors further point out that PCH and FIDA are completely equivalent in the way of modeling PSFs; that is, any modeling approach developed from one of them can always be applied to the other. It is also demonstrated that simplified FIDA and PCH formulas in the form of power series can be applied for fast and precise numerical calculations. The two methods are also compared for their merits in the calculation efficiency.


[The change of CD4+ CD25+ regulatory T cells in patients with rheumatoid arthritis].
To investigate the change of CD4+ CD25+ FoxP3+ regulatory T cells (Treg)in peripheral blood (PB)and synovial fluid (SF) in patients with rheumatoid arthritis (RA) and its role in RA immune tolerance imbalance. The frequency of CD4+ CD25+ FoxP3+ Treg in PB and SF cells in active RA patients and healthy volunteers were determined using flow cytometry. The expression of FoxP3 gene in mononuclear cells was analyzed by real-time PCR. The correlation between the frequency of CD4+ CD25+ FoxP3+ Treg in PB cells and disease activity indices was evaluated. (1) Active RA patients had a higher level of CD4+ CD25+ FoxP3+ Treg in SF cells (7.56% +/- 2.89%) than in PB cells (1.84% +/- 0.97%). Their level of CD4+ CD25+ FoxP3+ Treg in SF cells was also higher than that of healthy volunteers (2.19% +/- 0.54%). Anti-CCP antibody (ACPA) positive RA patients had a lower level of CD4+ CD25+ FoxP3+ Treg (1.40% +/- 0.63%) in PB cells compared with the ACPA negative RA patients (2.85 +/- 0.87%). (2) Active RA patients had a higher mRNA level of FoxP3 in SF mononuclear cells than those inactive RA patients and healthy volunteers (P < 0.01). (3) The frequency of CD4+ CD25+ FoxP3+ Treg in PB cells in active RA patients had no correlation with disease activity indices (P > 0.05). Altered frequency of CD4+ CD25+ FoxP3+ Treg in SF cells of RA patients might contribute to RA immune tolerance imbalance in inflammatory joints.


Decreased baroreflex sensitivity is linked to the atherogenic index, retrograde inflammation, and oxidative stress in subclinical hypothyroidism.
Purpose/aim of the study: The present study investigated the link of hyperlipidemia, inflammation and oxidative stress (OS) to cardiovascular (CV) risks in subclinical hypothyroidism (SCH). We enrolled 81 subclinical hypothyroid patients and 80 healthy subjects as control. Their CV and autonomic functions were assessed by spectral analysis of heart rate variability (HRV), continuous blood pressure variability (BPV) measurement and conventional autonomic function testing. Thyroid profile, lipid profile, immunological, inflammatory and OS markers were estimated and correlated with the baro-reflex sensitivity (BRS), the marker of sympathovagal imbalance (SVI) & CV risk. Mean arterial pressure (MAP, P<0.0001), total peripheral resistance (TPR, P<0.0001), ratio of low-frequency to high-frequency power of HRV (LF-HF ratio) (P<0.0001) were significantly higher and BRS (P<0.0001) was significantly lower in SCH group than the control group. BRS significantly correlated with heart rate, MAP, LF-HF ratio, lipid risk factors, anti-thyroperoxidase antibody, thyroid-stimulating hormone, high-sensitive C-reactive protein (hsCRP), malondialdehyde (MDA) and SCH. It was concluded that SVI is associated with SCH. Though dyslipidemia, inflammation and OS contributed to decreased BRS, SCH per se contributed maximally to it. Decreased BRS could be a physiological basis of increased CV risks in patients with SCH.


Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis.
To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori (H pylori) antibodies. Gastritis was assessed according to Sydney System. Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r = 0.2216, P = 0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.


Post-endodontic treatment periodontal surgery: a case report.
Two patients were diagnosed with combined endodontic-periodontal lesions. Endodontic treatment was performed, followed by surgery. In addition, the regeneration process was supported by the application of an enamel matrix derivate alone or in combination with guided bone regeneration techniques. At recall visits after 24 months, the teeth were asymptomatic and marked bone regeneration had occurred in both patients. The successful post-endodontic treatment of combined endodontic-periodontal lesions, using periodontal surgery and as adjunct guided tissue regenerative techniques, is presented. Further, the possibility of saving teeth, even with severely apparent pathology, should be highlighted.


[Phase II study with pirarubicin in pretreated progressive head-neck neoplasms].
Sixteen heavily pretreated patients (pts) (4 surgery + chemotherapie + radiotherapy; 4 chemotherapy + radiotherapy: 6 surgery + radiotherapy; 2 chemotherapy) and one previously untreated patient, who refused surgery and or radiotherapy, all with progressive disease, with advanced squamous cell carcinoma of the head and neck were included in a phase II study with pirarubicin 60 mg/m2 i.v. day 1 every 3-4 weeks (CT). All pts received at least one course of CT. 15 pts were evaluable for response, all 17 pts were evaluable for toxicity. Female (male ratio 1/16; mean age 56 (42-68) yrs, mean performance status 70% (50-70). Seventeen pts received a mean of 3 (1-8) courses, 2 pts had received only one course of CT. Response and toxicity were assessed according to WHO classification. Results after 1-8 courses of CT: 1 (7%) complete remission; 1 (7%) partial remission; 9 (60%) no change; 4 (26%) progressive disease. No toxicity of grade IV was observed. Mean duration of remission 16 weeks. Median survival time 7 (1-10) months. 9 pts died and 8 pts are alive; six of them had progressive disease.


[Demonstration of a reovirus in helicopter disease of broilers].
A reovirus was isolated from 5-13-day-old broiler birds with signs of the so-called helicopter disease--one of the forms of the malabsorption syndrome. A number of organs were investigated (trachea, liver, spleen, bursa of Fabricius, proventricular stomach, and tendon sheath of musculus gastrocnemius). The virus was isolated from the proventricular stomach and the tendon sheath in cell cultures of chick embryo kidney as well as in 5-7-day-old chick embryos inoculated in the yolk sac. The remaining organs proved virologically negative. All organs, including the primarily positive ones, were shown to be virologically negative upon the inoculation of chick embryo fibroblast cultures and of chorioallantoic membranes of 10-11-day-old chick embryos. The isolate was identified as an avian reovirus, and was denoted with the initials R-85--on the grounds of its biologic and physico-chemical properties, of its morphology (negative-contrast electron microscopy), and of its morphogenesis (ultrathin electron-microscopic cross sections). Investigated were the histopathologic changes in chick embryos inoculated with the R-85 reovirus and the pathologic changes in the liver of spontaneously affected birds.


[Quality of embryos in unexplained sterility].
In our study, the rate of pregnancy by transfer and puncture was not significantly different in unexplained and in tubal infertility, but the mean number of transferred embryos was significantly higher in the first group. To explain these data, we compared the quality of embryos in 32 punctures realized among 29 women with unexplained infertility and in 171 punctures planned among 156 women with tubal infertility. The percentage of embryos with 4 or more blastomeres was significantly lower in the unexplained infertility group than in the pure tubal infertility group.


Colour vision and visual ecology of the blue-spotted maskray, Dasyatis kuhlii Müller & Henle, 1814.
Relatively little is known about the physical structure and ecological adaptations of elasmobranch sensory systems. In particular, elasmobranch vision has been poorly studied compared to the other senses. Virtually nothing is known about whether elasmobranchs possess multiple cone types, and therefore the potential for colour vision, or how the spectral tuning of their visual pigments is adapted to their different lifestyles. In this study, we measured the spectral absorption of the rod and cone visual pigments of the blue-spotted maskray, Dasyatis kuhlii, using microspectrophotometry. D. kuhlii possesses a rod visual pigment with a wavelength of maximum absorbance (lambda(max)) at 497 nm and three spectrally distinct cone types with lambda(max) values at 476, 498 and 552 nm. Measurements of the spectral transmittance of the ocular media reveal that wavelengths below 380 nm do not reach the retina, indicating that D. kuhlii is relatively insensitive to ultraviolet radiation. Topographic analysis of retinal ganglion cell distribution reveals an area of increased neuronal density in the dorsal retina. Based on peak cell densities and using measurements of lens focal length made using laser ray tracing and sections of frozen eyes, the estimated spatial resolving power of D. kuhlii is 4.10 cycles per degree.


Recognition accuracy and reaction time of vocal expressions of emotion by African-American and Euro-American college women.
This study examined the relationship of racial group membership and vocal expressions of emotion. Recognition accuracy and reaction time were examined using the Diagnostic Assessment of Nonverbal Accuracy 2 Receptive Paralanguage subtests with 18 young Euro-American and African-American women. Participants listened to Euro-American children and adults speaking a neutral sentence, and identified the emotion as happy, sad, angry, or fearful. Analysis identified a significant effect for race on reaction time. Euro-American participants had faster mean RT than the African-American women for the recognition of vocal expression of emotion portrayed by Euro-Americans. However, no significant differences were found in mean accurate identification between the two groups. The finding of a significant difference in recognition RT but not in accuracy between the stimuli spoken by an adult and a child was unexpected. Both racial groups had faster mean RT in response to vocal expression of emotion by children.


The spatial distribution of exposed nuclear DNA in normal, cancer, and reverse-transformed cells.
The malignant CHO-K1 cell is reverse-transformed by cAMP, regaining the phenotype of a normal fibroblast. During this reaction, much of its DNA re-acquires sensitivity to hydrolysis by DNase I in a way characteristic of the normal fibroblast. Exposed DNA forms a rim about the nucleus in both the normal and reverse-transformed cell but not in the malignant CHO-K1. Reacquisition of the nuclear rim requires an organized cytoskeleton. Sequestered DNA forms families of different degrees of sequestration. In accordance with previous theoretical developments it is proposed that (i) genes specific to a given differentiation state are stored in the nuclear rim, whereas genes specific to other states are sequestered within the nucleus; (ii) only exposed genes are active, and their activity is modulated by regulatory molecules in the fluid medium; (iii) exposure and sequestration are regulated by cytoskeletal and nuclear protein structures; (iv) in at least several types of cancer the regulatory defect lies in the genome exposure process so that the specific DNA sequences and their associated growth regulatory loci have been transferred from the exposed to the sequestered condition with consequent loss of the nuclear rim of exposed DNA. The methodology described should be generally applicable to examining the accessibility state of subsets of DNA during various physiological modulations of cell function.


UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer.
High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.


Regulation of cell motility on polymer substrates via "dynamic," cell internalizable, ligand microinterfaces.
In vivo, motile epidermal tissues frequently encounter ligand microinterfaces that are dynamic, owing to rapid cell-mediated substrate phagocytosis. In this study, we have examined cell motility phenomena in response to the adhesion ligand, collagen, which was presented on cell-internalizable 400-nm colloidal gold microcarriers. Normal human keratinocytes were seeded onto collagen-adsorbed poly(lactide-co-glycolide) (PLGA) films that were predeposited with varying densities of the ligand-associated microcarriers (LAMs), such that the overall ligand density and the ligand loading per microcarrier were invariant. Cells seeded on LAMs exhibited rapid and distinct cytoskeletal redistribution resulting in numerous filopodial extensions, indicative of activation of cell motility processes. We report that the population-averaged cell migration rate of cells, mu, was increased from 2 microm2/min on collagen substrates lacking the microcarriers, to approximately 50 microm2/min on collagen presenting LAMs. An increase in LAM density to 1.2 LAMs per microm2 was found to maximize mu, as well as the directional persistence and speed of cell migration, whereas very high LAM densities saturated cell internalization and diminished migration rates. The cell-LAM interactions essential to enhanced migration were ligand-activated, as mu; values were reduced 400% on internalizable microcarriers lacking ligands; moreover, cooperative ligand elicitation was possible, for example, when 10 microg/mL soluble fibronectin was introduced as a costimulant of keratinocytes, yielding the highest reported mu values (80 microm2/min) on collagen LAM-PLGA substrates. Notably, cell migration rates were severely repressed when cell internalization processes were challenged through covalent conjugation of ligand carriers to the substrate, indicating that signals from cell-LAM binding alone were inadequate for elevated levels of cell migration. Further analysis indicated that the presence of LAMs did not alter the protease-resistant adhesivity between the cell and the underlying substrate, suggesting that the activation governing ligand interactions likely arose at the cell-LAM interface rather than the cell-substrate interface. This study highlights the novel use of secondary ligand-presenting microscale/nanoscale depots at polymer substrates to elicit, via dynamic cell internalization processes, significantly enhanced levels of cell migration over traditional interfaces with ligand-bearing substrates.


Allergic conjunctivitis: a survey of new antihistamines.
The objective of this study was to determine the therapeutic value of a wide variety of H1 antihistamines for potential ophthalmic use by performing ocular toxicity and efficacy tests in rabbits and humans. Fourteen antihistamines were formulated into ophthalmic preparations and were screened in the rabbit model; of these, thirteen were preliminary evaluated for toxicity and efficacy in humans. Based on comfort and efficacy, four (pheniramine, chlorpheniramine, dexbrompheniramine and pyrilamine) were selected for more extensive dose response and efficacy testing. 0.3% chlorpheniramine, dexbrompheniramine, pyrilamine and pheniramine significantly reduced histamine-induced itching (p less than or equal to 0.01 for each drug) and conjunctival injection (p less than or equal to 0.02 for each drug), when compared to contralateral eyes receiving PBS. When compared to 0.3% pheniramine in the fellow eye (mean difference score = 0.79 +/- 0.21), 0.3% chlorpheniramine (1.5 +/- 0.22; p = 0.04) and 0.3% dexbrompheniramine (1.71 +/- 0.18; p = 0.01) were superior in decreasing histamine-induced itching. Dose-response curves demonstrated that 0.4% and 0.5% pheniramine were statistically superior to 0.3% in relieving itching and redness. Compared to 0.3% pheniramine, 0.1% and 0.2% chlorpheniramine and 0.2% pyrilamine were statistically superior in inhibiting redness and itching. The results of this study suggest that 0.1%, 0.2% and 0.3% chlorpheniramine, 0.3% dexbrompheniramine, 0.2% pyrilamine, and 0.4% and 0.5% pheniramine were effective in relieving the itching and conjunctival injection associated with topically applied histamine. These seven formulations should be considered as possible new preparations for use as ophthalmic antihistamines and may warrant further evaluation.


[CASUS model trial. A computer-assisted author system for problem-oriented learning in medicine].
The CASUS-project, a three year publicly funded effort to improve the quality of continuing medical education in Germany, has one major goal: The development and evaluation of an easy-to-handle author-system for problem-oriented learning in medicine. On the theoretical basis of the cognitive apprenticeship-approach, the concept of a teaching and learning database as a hypermedia system was built. The student should learn to manage authentical problems in the form of authentical clinical cases. The step-by-step learning process is expert-guided by the clinical authors of each case. The creation of various differential diagnoses by the learner is strongly supported in the process. The structure of the program can also be used for case-based examinations. In parallel to the technical development, a case-selection process for medical students students in internal medicine was initiated. About 120 relevant diseases were identified to be represented in the CASUS-case library. Prevalence, transferability of knowledge, treatability, urgence of treatment and preventive aspects were used as selection criteria. The system will be evaluated during the implementation of test cases and will then be available to be used by authors and students on a routine basis in 1997.


Influence of Alkoxy Groups on the Photoinduced Dynamics of Organic Molecules Exemplified on Alkyl Vinyl Ethers.
A series of different alkyl vinyl ethers is investigated to decipher the possible reaction channels upon photoexcitation to the π3s-Rydberg and the ππ*-valence state at 200 nm using time-resolved photoelectron spectroscopy and on-the-fly time-dependent density functional theory dynamics simulations. The results indicate two possible relaxation pathways: (1) a radiationless decay through the ππ*-state back to the ground state via torsion of the C═C double bond, in accordance with the dynamics found in ethylene; and (2) a fast dissociation of the C-O bond between the alkyl and the vinoxy group in the πσ*-state. The latter state can be accessed only after excitation to the π3s-Rydberg state (quantum yield of ∼50% according to the dynamics simulations). Additionally, the excited state barrier leading to formation of a vinyl radical was found to be too high to be crossed. These results indicate that the dynamics of ethers crucially depend on the excitation wavelength and that the πσ*-state constitutes an important competitive reaction channel that leads to dissociation of the molecules.


Fermentation characteristics of some assamica clones and process optimization of black tea manufacturing.
Changes in the specific activities of polyphenol oxidase (PPO), peroxidase (POD), and protease and in the relative amounts of flavan-3-ols for eight genetically derived cultivated teas at various stages of leaf maturity and in four succescive seasons were examined. A series of investigations were carried out to study the cross-reactivity of complex polyphenols and PPO-generated orange-yellow theaflavins, as well as of POD oxidized substrates, producing brown so-called thearubigins during fermented tea processing. From the estimation of five major catechins, PPO activities in young shoots, and theaflavin and thearubigin contents of crushed, torn, and curled (CTC) black teas, the superior variety and flavorful flush characteristics were refined. Notable protein hydrolysis by endogenous protease as measured from free amino acids and formation of tannin-protein complex (browning products) was obtained for cultivar character and product quality. Results showed that process optimization with respect to time, temperature, moisture, and pH maximizes PPO-catalyzed desirable theaflavin pigments, whereas POD-mediated chemical reaction produces dull color.


TraA and its N-terminal relaxase domain of the Gram-positive plasmid pIP501 show specific oriT binding and behave as dimers in solution.
TraA is the DNA relaxase encoded by the broad-host-range Grampositive plasmid pIP501. It is the second relaxase to be characterized from plasmids originating from Gram-positive organisms. Full-length TraA (654 amino acids) and the N-terminal domain (246 amino acids), termed TraAN246, were expressed as 6xHis-tagged fusions and purified. Small-angle X-ray scattering and chemical cross-linking proved that TraAN246 and TraA form dimers in solution. Both proteins revealed oriTpIP501 (origin of transfer of pIP501) cleavage activity on supercoiled plasmid DNA in vitro. oriT binding was demonstrated by electrophoretic mobility shift assays. Radiolabelled oligonucleotides covering different parts of oriTpIP501 were subjected to binding with TraA and TraAN246. The KD of the protein-DNA complex encompassing the inverted repeat, the nick site and an additional 7 bases was found to be 55 nM for TraA and 26 nM for TraAN246. The unfolding of both protein constructs was monitored by measuring the change in the CD signal at 220 nm upon temperature change. The unfolding transition of both proteins occurred at approx. 42 degrees C. CD spectra measured at 20 degrees C showed 30% a-helix and 13% b-sheet for TraA, and 27% alpha-helix and 18% beta-sheet content for the truncated protein. Upon DNA binding, an enhanced secondary structure content and increased thermal stability were observed for the TraAN246 protein, suggesting an induced-fit mechanism for the formation of the specific relaxase-oriT complex.


Evaluation of optical detection platforms for multiplexed detection of proteins and the need for point-of-care biosensors for clinical use.
This review investigates optical sensor platforms for protein multiplexing, the ability to analyze multiple analytes simultaneously. Multiplexing is becoming increasingly important for clinical needs because disease and therapeutic response often involve the interplay between a variety of complex biological networks encompassing multiple, rather than single, proteins. Multiplexing is generally achieved through one of two routes, either through spatial separation on a surface (different wells or spots) or with the use of unique identifiers/labels (such as spectral separation-different colored dyes, or unique beads-size or color). The strengths and weaknesses of conventional platforms such as immunoassays and new platforms involving protein arrays and lab-on-a-chip technology, including commercially-available devices, are discussed. Three major public health concerns are identified whereby detecting medically-relevant markers using Point-of-Care (POC) multiplex assays could potentially allow for a more efficient diagnosis and treatment of diseases.


Improvement of lipid and lipoprotein profiles in children and adolescents with cystic fibrosis on CFTR modulator therapy.
Association of a high-fat diet with increased risks of cardiovascular disease (CVD) and type 2 diabetes, has prompted evaluation of lipids in people with CF (pwCF). However, most evidence on dyslipidemia was published before CF transmembrane conductance regulator (CFTR) modulators became a standard of care. The main goal of this study was to investigate the effect of CFTR modulator therapies on lipid and lipoprotein profiles in children and adolescents with CF. Blood samples were collected from 153 pwCF (10.1 ± 4.7 years of age) and 60 age-matched controls. Most pwCF were pancreatic insufficient on pancreatic enzyme replacement therapy. By the end of the study, 65% of CF participants were on CFTR modulator therapy for >1 month. The results of traditional and advanced lipid testing in pwCF were correlated with clinical and dietary information. Total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly lower in pwCF compared to non-CF participants. Those not receiving CFTR modulators also had significantly lower high-density lipoprotein (HDL) cholesterol and HDL particle number than controls. Individuals with CF on modulator therapy had significantly higher concentrations of anti-atherogenic HDL cholesterol and HDL particles along with lower levels of atherogenic large very-low density lipoprotein (VLDL) particles, total and small LDL particles, and triglycerides compared to those without CFTR modulator therapy. CFTR modulator therapy has a beneficial effect on dyslipidemia in CF. It remains to be seen if these positive changes translate into decreased CVD risk later in life given the increasing life expectancy in CF.


A Review of Developments in Polymer Stabilized Liquid Crystals.
Polymer-stabilized liquid crystals (PSLCs) are multi-functional materials consisting of polymer networks in a continuous phase of liquid crystals (LCs), of which polymer networks provide anchoring energy to align the LCs. A number of improvements are detailed, including polymer-stabilized nematic liquid crystals (PSNLCs), polymer-stabilized cholesteric liquid crystals (PSCLCs), polymer-stabilized blue phase liquid crystals (PSBPLCs), polymer-stabilized smectic liquid crystals (PSSLCs), polymer-stabilized ferroelectric liquid crystals (PSFLCs), and polymer-stabilized antiferroelectric liquid crystals (PSAFLCs) in this review. Polymer stabilization has achieved multiple functionalities for LCs; in smart windows, a sufficiently strong electric field allows the LCs to reorient and enables switching from a scattering (transparent) state to a transparent (scattering) state. For broadband reflectors, the reflection bandwidth of LCs is manually tuned by electric fields, light, magnetic fields, or temperature. PSBPLCs open a new way for next-generation displays, spatial light modulators, sensors, lasers, lenses, and photonics applications. Polymer networks in PSFLCs or PSAFLCs enhance their grayscale memories utilized in flexible displays and energy-saving smart cards. At the end, the remaining challenges and research opportunities of PSLCs are discussed.


Sex workers and the issues surrounding registration in Turkey.
Awareness of the activities of commercial sex workers can be an important step toward understanding the transmission of sexually transmitted infections (STIs) in developing countries. This study discusses how sex workers are viewed in Turkey and the process of mandatory registration. To support the information provided and the conclusions drawn, a sample of 150 sex workers who made regular visits to a STI hospital was interviewed. Information on socio-demographic characteristics, family and support information and certain risk behaviors were solicited. Recommendations for increasing preventive education are made, with considerations for increased attention and support for this group of individuals.


Inflammatory changes of the gastric mucosa and serum concentration of chosen growth factors in children.
To assess whether there is a correlation between the severity of gastritis and concentration of chosen growth factors in the serum of children infected with H. pylori. The study included 64 children of whom 50% (Group I) were infected with H. pylori and had gastritis; 18.7% (Group II) of the examined children had a positive titre of IgG against H. pylori and normal gastric mucosa. Controls (Group III) comprised 31.3%. The gastric mucosa was evaluated histopathologically according to the Sydney System. The serum concentrations of growth factors: EGF, TGF-alpha, VEGF, were determined using ELISA. Mean concentrations of the growth factors were also the highest in Group I compared to Group II and Group III (EGF - 137.3+/-10.4 pg/mL, TGF-alpha - 0.4+/-1.2 pg/mL, VEGF - 146.8 pg/mL). Analysis of correlations between growth factors and the severity of gastritis as well as the activity of antral gastric mucosa inflammation proved that mean EGF concentration in H. pylori infected children was the highest (149.5+/-84.8 pg/mL) in severe gastritis, whereas mean concentrations of TGF-alpha (2.0+/-4.3 pg/mL) and of VEGF (148.1+/-92.6 pg/mL) were the highest in moderate gastritis. Mean concentrations of EGF (155.1+/-116.4 pg/mL) and of VEGF (156.0+/-118.9 pg/mL) were the highest in high activity antral gastritis, whereas the mean concentration of TGF-alpha was the highest (2.0+/-4.2 pg/ml) in moderate activity gastritis. In the children with H. pylori infection, serum concentrations of EGF, TGF-alpha, VEGF were the highest in moderate and severe antral gastritis.


Platelet testing to guide aspirin dose adjustment in pediatric patients after cardiac surgery.
Thrombosis is associated with increased morbidity and mortality in pediatric patients undergoing cardiac surgery. Although aspirin commonly is used for thromboprophylaxis, the utility of laboratory-based tests that assess aspirin efficacy have not been evaluated. We sought to determine the relationship between platelet aggregation testing and aspirin dose adjustment on thrombosis rates in this population. Pediatric patients undergoing cardiac surgery who received aspirin and underwent platelet testing were studied retrospectively. Patients were excluded if they were treated with multiple agents or experienced thrombosis before the initiation of aspirin. Thrombosis events within 30 days after initiation of aspirin were recorded. Associations between aspirin responsiveness and thrombosis rate and aspirin dose adjustment and thrombosis rate were assessed with the use of multivariable logistic regression analysis. Suboptimal platelet response to aspirin was detected in 64 of 430 patients (15%) and thrombosis was detected in 11 patients (2.6%). Lack of aspirin responsiveness on initial testing was a significant risk factor for thrombosis (P < .001) independent of age, weight, diagnosis, and initial aspirin dose. Dose escalation based on aspirin testing was performed in 40 of 64 patients, and significantly lower rate of thrombosis was observed in patients who underwent dose escalation compared with those without dose escalation (0/40 vs 9/24, P < .001). By multivariable analysis, the only significant independent risk factor for thrombosis was failure to increase aspirin dose after initial unresponsiveness (P < .001). Current practice of weight-based aspirin dosing may lead to subtherapeutic platelet inhibition in some children. Aspirin unresponsiveness is associated with increased risk of thrombosis after specific pediatric cardiac surgical procedures. Aspirin dose increase in unresponsive patients is associated with reduced risk of thrombosis.


Biomechanical considerations in slipped capital femoral epiphysis and insights into prophylactic fixation.
Slipped capital femoral epiphysis (SCFE) is a deformity of the proximal femur secondary to widened and unstable physis. In stabilising the slip, gold standard treatments stop growth and involve premature physeal closure, which prevents the remodelling of the acquired deformity and creates a leg length discrepancy that may be significant in younger patients. We measured the impact of placing threaded screws across the proximal femoral physis by measuring the centre-trochanteric distance (CTD) and articulo-trochanteric distance (ATD) in participants with or without prophylactic fixation. We then compared the mechanical performance of static (stainless and titanium cannulated Synthes screws) and potentially growing implants (Synthes SCFE screw and Pega Medical Free Gliding screw) in a validated synthetic bone model. In the review of 30 non-fixed and 60 fixated hips over a mean follow-up of 1.9 years, we have noted a significant difference in pre/post CTD and ATD, as well as the change in CTD and ATD over time. In the biomechanical study, the newer implants allowing growth (Synthes SCFE screw and Pega Medical Free Gliding screw) were both shown to be at least non-inferior. The primary deformity of a SCFE in itself alters hip mechanics. Also, as confirmed in this study, there is a secondary deformity that is created by static fixation and relative trochanteric overgrowth. To help remodel mild deformities and prevent secondary trochanteric overgrowth, growing implants seem to be non-inferior to the more standard means of fixation in static testing.


Myalgia and biochemical changes following suxamethonium after induction of anaesthesia with thiopentone or propofol.
The incidence and severity of muscle pains and changes in creatine kinase were assessed following administration of 1 mg.kg-1 suxamethonium either immediately or 2 min after induction of anaesthesia with propofol or thiopentone in patients undergoing elective dental and ophthalmic surgery. The incidence of muscle pains was 35 and 60% respectively in the groups given suxamethonium immediately and 2 min after propofol, and 35 and 55% when given immediately and 2 min after thiopentone, with no statistically significant differences among the groups. Creatine kinase levels increased in all the groups after operation with the least average increase in the group receiving suxamethonium immediately after propofol and the highest increase in the group receiving suxamethonium 2 min after thiopentone. There was no correlation between the incidence and severity of fasciculations, muscle pains and changes in creatine kinase within or between the groups. It is concluded that neither the induction agent nor the time between the induction agent and suxamethonium administration has any significant influence on the incidence of muscle pains or creatine kinase elevation following suxamethonium.


High content screening of a kinase-focused library reveals compounds broadly-active against dengue viruses.
Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates.


Deciphering the catalytic machinery in 30S ribosome assembly GTPase YqeH.
YqeH, a circularly permuted GTPase (cpGTPase), which is conserved across bacteria and eukaryotes including humans is important for the maturation of small (30S) ribosomal subunit in Bacillus subtilis. Recently, we have shown that it binds 30S in a GTP/GDP dependent fashion. However, the catalytic machinery employed to hydrolyze GTP is not recognized for any of the cpGTPases, including YqeH. This is because they possess a hydrophobic substitution in place of a catalytic glutamine (present in Ras-like GTPases). Such GTPases were categorized as HAS-GTPases and were proposed to follow a catalytic mechanism, different from the Ras-like proteins. MnmE, another HAS-GTPase, but not circularly permuted, utilizes a potassium ion and water mediated interactions to drive GTP hydrolysis. Though the G-domain of MnmE and YqeH share only approximately 25% sequence identity, the conservation of characteristic sequence motifs between them prompted us to probe GTP hydrolysis machinery in YqeH, by employing homology modeling in conjunction with biochemical experiments. Here, we show that YqeH too, uses a potassium ion to drive GTP hydrolysis and stabilize the transition state. However, unlike MnmE, it does not dimerize in the transition state, suggesting alternative ways to stabilize switches I and II. Furthermore, we identify a potential catalytic residue in Asp-57, whose recognition, in the absence of structural information, was non-trivial due to the circular permutation in YqeH. Interestingly, when compared with MnmE, helix alpha2 that presents Asp-57 is relocated towards the N-terminus in YqeH. An analysis of the YqeH homology model, suggests that despite such relocation, Asp-57 may facilitate water mediated catalysis, similarly as the catalytic Glu-282 of MnmE. Indeed, an abolished catalysis by D57I mutant supports this inference. An uncommon means to achieve GTP hydrolysis utilizing a K(+) ion has so far been demonstrated only for MnmE. Here, we show that YqeH also utilizes a similar mechanism. While the catalytic machinery is similar in both, mechanistic differences may arise based on the way they are deployed. It appears that K(+) driven mechanism emerges as an alternative theme to stabilize the transition state and hydrolyze GTP in a subset of GTPases, such as the HAS-GTPases.


In the setting of β-cell stress, the pancreatic duct gland transcriptome shows characteristics of an activated regenerative response.
The pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche based on its coiled tubular structure embedded in mesenchyme, its proliferation and expansion in response to pancreatic injury, and the fact that it contains endocrine and exocrine epithelial cells. Little is known of the molecular signature of the PDG compartment in either a quiescent state or the potentially activated state during β-cell stress characteristic of diabetes. To address this, we performed RNA sequencing on RNA obtained from PDGs of wild-type vs. prediabetic HIP rats, a model of type 2 diabetes. The transcriptome of the PDG compartment, compared with a library of 84 tissue types, placed PDGs midpoint between the exocrine and endocrine pancreas and closely related to seminiferous tubules, consistent with a role as a stem cell niche for the exocrine and endocrine pancreas. Standard differential expression analysis (permissive threshold P < 0.005) identified 245 genes differentially expressed in PDGs from HIP rats vs. WT rats, with overrepresentation of transcripts involved in acute inflammatory responses, regulation of cell proliferation, and tissue development, while pathway analysis pointed to enrichment of cell movement-related pathways. In conclusion, the transcriptome of the PDG compartment is consistent with a pancreatic stem cell niche that is activated by ongoing β-cell stress signals. The documented PDG transcriptome provides potential candidates to be exploited for lineage tracing studies of this as yet little investigated compartment. NEW & NOTEWORTHY The pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche. Transcriptome analysis of the PDG gland placed it midpoint between exocrine and endocrine tissues with adaptation toward response to inflammation and increased cell movement in a model of type 2 diabetes with ongoing β-cell apoptosis. These findings support the proposal that PDGs may act as a pancreatic stem cell niche.


Studies of bilirubin kinetics in normal adults.
This report describes studies of bilirubin kinetics in 13 healthy young adults. The plasma content of unconjugated bilirubin-(14)C was determined at frequent intervals for 24-30 hr after the intravenous injection of a tracer dose of unconjugated isotopic bilirubin. Fecal and urinary radioactivity were measured for 7 days. During this time cumulative recovery averaged 96% of the injected dose. The plasma curves were processed by digital computer. For the 30 hr experimental period, a sum of three exponentials, with average half-times of 18, 81, and 578 min, was required to describe the data. Using the plasma curve integral method, the hepatic bilirubin clearance (47 +/-10 ml/min, mean +/-SD), the bilirubin production rate (3.8 +/-0.6 mg/kg per day), and the mean red blood cell life span (101 +/-13 days) were calculated directly from the parameters of this function. To gain further insight into the metabolism of unconjugated bilirubin, the data were also used to determine the parameters of a multicompartmental model. In the model proposed, plasma unconjugated bilirubin exchanges with two additional pools one of which is thought to represent extrahepatic extravascular, and the other intrahepatic unconjugated bilirubin. Bilirubin is eliminated from the system via the proposed intrahepatic pool. From the data and the model, pool sizes and exchange rates between compartments were calculated, and the liver: plasma concentration gradient estimated. These studies provide a detailed analysis of the kinetics of unconjugated bilirubin in a healthy normal population and are intended to serve as a reference point for studies of abnormal states.


Fractional topological insulators.
We analyze generalizations of two-dimensional topological insulators which can be realized in interacting, time reversal invariant electron systems. These states, which we call fractional topological insulators, contain excitations with fractional charge and statistics in addition to protected edge modes. In the case of s(z) conserving toy models, we show that a system is a fractional topological insulator if and only if sigma(sH)/e* is odd, where sigma(sH) is the spin-Hall conductance in units of e/2pi, and e* is the elementary charge in units of e.