Separation of the molecular species of diacyl and alkenylacyl subclasses of the methyl ester of dinitrophenylethanolamine glycerophospholipid by high-performance liquid chromatography.
A high-performance liquid chromatographic (HPLC) procedure for the separation of the molecular species of alkenylacyl and diacyl subclasses after the derivatization of ethanolamine glycero-phospholipids (EGP) to the methyl ester of the dinitrophenylated lipids is described. Methyl esters of dinitrophenylethanolamine glycerophospholipids were first separated into alkenylacyl, alkylacyl and diacyl subclasses by thin-layer chromatography, then each subclass was separated into individual molecular species by reversed-phase HPLC. By converting the EGP into UV-absorbing derivatives, it proved possible to utilize the specificity of spectrophotometric detection for the determination of the individual molecular species. Alkenylacyl and diacyl derivatives were resolved into fifteen to twenty different species in a single HPLC run. The method should facilitate studies on the metabolism of the polar head group of both molecular species of alkenylacyl and diacyl glycerophosphoethanolamine in a variety of tissues using radioactive precursors.


Heat shock factor 1 prevents the reduction in thrashing due to heat shock in Caenorhabditis elegans.
Heat shock factor 1 (HSF-1) is activated by heat stress and induces the expression of heat shock proteins. However, the role of HSF-1 in thermotolerance remains unclear. We previously reported that heat stress reversibly reduces thrashing movement in Caenorhabditis elegans. In this study, we analyzed the function of HSF-1 on thermotolerance by monitoring thrashing movement. hsf-1 RNAi suppressed the restoration of thrashing reduced by heat stress. In contrast, hsf-1 knockdown cancelled prevention of movement reduction in insulin/IGF-1-like growth factor 1 receptor (daf-2) mutant, but didn't suppress thrashing restoration in daf-2 mutant. In addition, hsf-1 RNAi accelerated the reduction of thrashing in heat-shocked wild-type C. elegans. And, daf-16 KO didn't accelerate the reduction of thrashing by heat stress. Taken together, these results suggest that HSF-1 prevents the reduction of thrashing caused by heat shock.


Acetyl-CoA synthetase overexpression in Escherichia coli demonstrates more efficient acetate assimilation and lower acetate accumulation: a potential tool in metabolic engineering.
The overexpression of acetyl-CoA (CoA) synthetase (ACS) in Escherichia coli showed significant reduction in acetate during glucose fermentation. It also greatly enhanced acetate assimilation when acetate was used as a carbon source. These features are ideal for applications in metabolic engineering. ACS overexpression can be strategically applied to reduce acetate byproduct, recover wasted carbon, and redirect carbon flux toward more favorable pathways. The native acs gene was cloned and overexpressed in E. coli. Studies showed significant effects on acetate production and assimilation in cultures grown in minimal and complex media with glucose or acetate as the carbon source.


Psychosocial Well-Being of Siblings of Pediatric Patients in Palliative Home Care.
Despite the proposed high burden of siblings of children and adolescents with life-limiting conditions receiving pediatric palliative care (PPC) at home, little is known about their psychosocial well-being. In this prospective, cross-sectional trial siblings of patients of a large pediatric palliative home care team were asked to answer the KINDL survey of health-related quality of life, the strengths and difficulties questionnaire (SDQ) to assess problems and resources of children and adolescents as well as the LARES questionnaire, a potential tool for early screening of distress in siblings of chronically ill children. The results of the KINDL total and subdomains as well of the SDQ-subdomains were compared to recent German normative data using multiple t-tests. In total, 44 siblings (28 female; age 7-18 years, mean 11.8 ± 3.03) of 29 families participated in this study. The subgroup which matches the age range of current normative data of 11-17 years old siblings (n = 25) reported a significant lower total quality of life as measured by KINDL in comparison to normative data. Subscale analyses revealed a significant lower physical and psychological well-being and self-esteem. Siblings of PPC patients yielded significant higher scores in the subdomain prosocial behavior compared to normative data as measured by the SDQ. Siblings of children receiving PPC in a home care setting are at risk for a relevant impairment of their health-related quality of life. Future studies should address the potential for possible interventions specific for this population-at-risk.


The evolution of group-level pathogenic traits.
A group-selection model for the evolutionary origin of phase-variation in E. coli is proposed. Populations of commensal strains of E. coli populating mammalian hosts modulate its immune defenses through population-level control of the expression of fimbriae. At any time only a proportion of the population expresses these cell-surface adhesins. Collectively they elicit a host-based nutrient release if the fimbriae expression is low. Too high levels of fimbriation would provoke an inflammatory response and thus intolerable conditions for the cells. The optimal level of fimbriation is a group property and its evolution is difficult to explain by naive individual selection scenarios. This article presents a computational model to simulate the evolution of fimbriae. The two main conclusions of this contribution are: (i) the evolution of this group property requires the population to be partitioned into weakly interacting sub-populations. (ii) Given certain scenarios evolution consistently under-performs, in the sense that it does not find the optimal level of fimbriation.


Hemostatic disorders in patients with infective endocarditis undergoing urgent surgical valve replacement - Rethinking current beliefs.
Although infective endocarditis (IE) represents a unique model of thrombo-inflammatory disease, the most frequent early complications of surgical valve replacement (SVR) in IE population are coagulopathy and bleeding. The hemostatic capacity and procedure-related coagulation disorders of IE patients undergoing SVR are unknown. The aims of this study were to test periprocedural hemostasis in IE patients undergoing urgent SVR, and to assess the association between disorders of hemostasis and early bleeding as well as with thromboembolic events. A prospective, two-center, hypothesis generating, observational study was performed between Dec 2017 and Jan 2020. Periprocedural hemostasis of IE patients was assessed using Total Thrombus-formation Analysis System (T-TAS Plus) within 24 h before and 72 h post SVR. Overall, 25 patients with active IE undergoing urgent SVR were tested. Hemostatic capacity of IE patients was significantly impaired pre-SVR as well as post-SVR compared to normal values, in most aspects of T-TAS assays under high and low shear forces, including prolonged activation of coagulation (T10), final clot formation (OT) and clot strength (AUC30). Post-SVR T-TAS results were significantly associated with early bleeding and with red blood cell, platelet, and fresh frozen plasma administration. No association with thrombo-embolic events was found. Patients with active IE undergoing urgent SVR have significantly reduced hemostatic capacity before and after SVR. Hemostatic insufficiency post-SVR is related to bleeding and blood products transfusion. T-TAS may be helpful in assessment of periprocedural hemostasis in patients with IE undergoing SVR.


The influence of attention on visual evoked potentials in normal adults and dementias.
In normal subjects (n = 58, 22-71 y) the influence of the attention level on the VEP latency is studied, as is done in an additional small group of dementias (n = 14). The motor reaction time test (MRT) was selected to measure the attention level. The MRT was administered simultaneously with the VEP (checkerboard pattern reversal). By comparing VEP in test and non-test situations it proved that administration of MRT during VEP examination does not influence the VEP latencies. In dementias the motor reaction time is delayed but the degree of MRT delay did not correlate with the VEP latencies. This holds true for healthy volunteers as well as for demented patients. It is thus concluded that the latency increase of the late peaks of the VEP in dementias cannot be attributed to attentional deficits.


Emergency department experience with sudden death: a survey of survivors.
Sudden death in the emergency department occurs frequently. Intervention by ED support staff may have a significant impact on the survivor's grief response. This study was undertaken to assess sudden death survivors' perceptions and satisfaction with their ED experience, as well as to identify potential weaknesses in their management. Family members of 66 patients who died in the ED from January 1980 to March 1985 were surveyed by telephone interview regarding the care they, as survivors, received while in the ED. Forty-seven of 66 (71%) were satisfied, 19 of 66 (29%) believed that their family received average or worse than average care. Thirty-seven of 66 (56%) survivors viewed the deceased in the ED; five regretted this. Twenty-nine survivors did not view; seven (24%) had regrets. Participants were questioned about attitudes expressed by the ED staff. Most responses were favorable, but a significant number thought the staff cold, unsympathetic, and not reassuring. Areas of apparent survivor dissatisfaction are discussed.


Antibacterial activity of Lactobacillus species against Vibrio species.
Forty-one Lactobacillus strains were tested for antagonistic activity against nine strains of Vibrio. L. plantarum and L. casei were the most effective, and L. brevis was the least effective in inhibiting the growth of Vibrio species. L. gasseri and L. helveticus strains showed higher activity, while L. reuteri and L. fermentum showed lower inhibitory activity against Vibrio species. L. acidophilus strains exhibited various degrees of antagonistic activities against Vibrio species. However, none of the Lactobacillus species were able to inhibit the growth of Salmonella enteritidis, S. typhimurium, Escherichia coli, and Staphylococcus aureus. Inhibition of the Vibrio species was probably due to the production of organic acids by the Lactobacillus species.


An ab initio mechanism for efficient population of triplet states in cytotoxic sulfur substituted DNA bases: the case of 6-thioguanine.
The deactivation mechanism of the cytotoxic 6-thioguanine, the 6-sulfur-substituted analogue of the canonical DNA base, is unveiled by ab initio calculations. Oxygen-by-sulfur substitution leads to efficient population of triplet states-the first step for generating singlet oxygen-which is responsible for its cytotoxicity.


Regulating Crystal Packing by Terminal tert-Butylation for Enhanced Solid-State Emission and Efficacious Charge Transport in an Anthracene-Based Molecular Crystal.
Organic semiconductors with combinative high carrier mobility and efficient solid-state emission are full of challenges but urgently pursued for developing new emerging optoelectronics. Herein, by delicately regulating the crystal packing of an anthracene-based molecular crystal via terminal tert-butylation, we developed a superior high mobility emissive molecule, 2,6-di(6-tert-butylnaphthyl)anthracene (TBU-DNA). The unique "slipped herringbone" packing motif of TBU-DNA enables its appropriate exciton-exciton coupling and electron-phonon coupling, thus resulting in remarkably high solid-state emission (photoluminescence quantum yield, ΦF ≈74.9 %) and efficacious charge transport (carrier mobility, μ=5.0 cm2 V-1 s-1 ). Furthermore, OLETs based on TBU-DNA show an external quantum efficiency (EQE) of 1.8 %, which is among the highest EQE values for single component OLETs reported till now. This work presents a crystal engineering strategy via exquisite molecular design to realize high mobility emissive organic semiconductors.


CircTNPO1 promotes the tumorigenesis of osteosarcoma by sequestering miR-578 to upregulate WNT5A expression.
As a type of non-coding RNAs, circular RNAs (circRNAs) have the ability to bind to miRNAs and regulate gene expression. Recent studies have shown that circRNAs are involved in certain pathological events. However, the expression and functional role of circTNPO1 in osteosarcoma (OS) are not yet clear. To investigate circRNAs that are differentially expressed in OS tissues and cells, circRNA microarray analysis combined with qRT-PCR was performed. The in-vitro and in-vivo functions of circTNPO1 were studied by knocking it down or overexpressing it. The binding and regulatory relationships between circTNPO1, miR-578, and WNT5A were evaluated using dual luciferase assays, RNA pull-down and rescue assays, as well as RNA immunoprecipitation (RIP). Furthermore, functional experiments were conducted to uncover the regulatory effect of the circTNPO1/miR-578/WNT5A pathway on OS progression. Cytoplasm was identified as the primary location of circTNPO1, which exhibited higher expression in OS tissues and cells compared to the corresponding controls. The overexpression of circTNPO1 was found to enhance malignant phenotypes in vitro and increase oncogenicity in vivo. Moreover, circTNPO1 was observed to sequester miR-578 in OS cells, resulting in the upregulation of WNT5A and promoting carcinoma progression. These findings indicate that circTNPO1 can contribute to the progression of OS through the miR-578/WNT5A axis. Therefore, targeting the circTNPO1/miR-578/WNT5A axis could be a promising therapeutic strategy for OS.


Determination of amphetamine-related compounds by high-performance liquid chromatography with chemiluminescence and fluorescence detections.
High-performance liquid chromatography with chemiluminescence detection has been established for the determination of trace levels of amphetamine-related compounds (APs) after fluorigenic derivatization. Bis(2,4,6-trichlorophenyl) oxalate and hydrogen peroxide in acetonitrile was used as a post-column chemilumigenic reagent. As derivatization reagents, dansyl chloride (Dns-Cl), 4-fluoro-7-nitrobenzoxadiazole (NBD-F) and naphtalene-2,3-dicarbaldehyde (NDA) were compared. Dns-Cl was the most suitable of the three for the simultaneous determination of both primary and secondary amino APs. The on-column detection limits for Dns-derivatives were 3.10(-15) - 4.10(-15) mol. NDA gave the most sensitive derivatives (cyanobenz[f]isoindole, CBI derivatives) with only primary amino APs. The detection limits for CBI derivatives were as low as 2.10(-16) mol. The present method was applied to the determination of methamphetamine in human urine. Only diethyl ether extraction was necessary as a clean-up treatment before Dns derivatization, because diethyl ether extracted methamphetamine quantitatively from urine at strong alkaline pH and the extract showed few interfering peaks around the retention time of methamphetamine after the derivatization. Methamphetamine concentrations as low as 1.10(-7) M in urine were determined after the above treatments.


Isolation, structure and fatty acid synthesis inhibitory activities of platensimycin B1-B3 from Streptomyces platensis.
Platensimycins B(1)-B(3) are natural congeners of platensimycin with modest to significant changes in the benzoic acid portion of the molecule, leading to attenuation in the biological activities and thus confirming the significance of the free carboxylate for the potent activity.


Natural 15N abundance of presumed N2-fixing and non-N2-fixing plants from selected ecosystems.
The 15N/14N ratios of plant and soil samples from Northern California ecosystems were determined by mass spectrometry. The 15N abundance of 176 plant foliar samples averaged 0.0008 atom % 15N excess relative to atmospheric N2 and ranged from-0.0028 to 0.0064 atom % 15N excess relative to atmospheric N2. Foliage from reported N2-fixing species had significantly lower mean 15N abundance (relative to atmospheric N2 and total soil N) and significantly higher N concentration (% N dry wt.) than did presumed non-N2-fixing plants growing on the same sites. The mean difference between N2-fixing species and other plants was 0.0007 atom % 15N. N2-fixing species had lower 15N abundance than the other plants on most sites examined despite large differences between sites in vegetation, soil, and climate. The mean 15N abundance of N2-fixing plants varied little between sites and was close to that of atmospheric N2. The 15N abundance of presumed non-N2-fixing species was highest at coastal sites and may reflect an input of marine spray N having relatively high 15N abundance. The 15N abundance of N2-fixing species was not related to growth form but was for other plants. Annual herbaceous plants had highest 15N abundance followed in decreasing order by perennial herbs, shrubs, and trees. Several terrestrial ferns (Pteridaceae) had 15N abundances comparable to N2-fixing legumes suggesting N2-fixation by these ferns. On sites where the 15N abundance of soil N differs from that of the atmosphere, N2-fixing plants can be identified by the natural 15N abundance of their foliage. This approach can be useful in detecting and perhaps measuring N2-fixation on sites where direct recovery of nodules is not possible.


Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks.
Implantable cardioverter defibrillator (ICD) use reduces mortality in patients with serious ventricular arrhythmias compared with antiarrhythmic drug (AAD) use. However, the relative impact of these therapies on self-perceived quality of life (QoL) is unknown. Three self-administered instruments were used to measure generic and disease-specific QoL in Antiarrhythmics Versus Implantable Defibrillators trial participants. Generalized linear models were used to assess the relationships between self-perceived QoL and treatment (AAD versus ICD) and adverse symptoms and ICD shocks. To minimize the impact of missing data, only patients surviving 1 year were included in the primary analyses. Baseline characteristics among QoL participants (n=905) and nonparticipants (n=111) were similar, but participants who survived 1 year (n=800) were healthier at baseline than nonsurvivors (n=105). Of the 800 patients in the primary analysis, characteristics of those randomized to AAD (n=384) versus ICD (n=416) were similar. Overall, ICD and AAD use were associated with similar alterations in QoL. The development of sporadic shocks and adverse symptoms were each associated with reduced physical functioning and mental well-being and increased concerns among ICD recipients, whereas development of adverse symptoms was associated with reduced physical functioning and increased concerns among AAD recipients. ICD and AAD therapy are associated with similar alterations in self-perceived QoL over 1-year follow-up. Adverse symptoms were associated with reduced self-perceived QoL in both groups, and sporadic shocks were associated with reduced QoL in ICD recipients.


Tactile display of softness on fingertip.
Multi-sensory human-machine interfaces are currently challenged by the lack of effective, comfortable and affordable actuation technologies for wearable tactile displays of softness in virtual- or augmented-reality environments. They should provide fingertips with tactile feedback mimicking the tactual feeling perceived while touching soft objects, for applications like virtual reality-based training, tele-rehabilitation, tele-manipulation, tele-presence, etc. Displaying a virtual softness on a fingertip requires the application of quasi-static (non-vibratory) forces via a deformable surface, to control both the contact area and the indentation depth of the skin. The state of the art does not offer wearable devices that can combine simple structure, low weight, low size and electrically safe operation. As a result, wearable softness displays are still missing for real-life uses. Here, we present a technology based on fingertip-mounted small deformable chambers, which weight about 3 g and are pneumatically driven by a compact and cost-effective unit. Weighting less than 400 g, the driving unit is easily portable and can be digitally controlled to stimulate up to three fingertips independently. Psychophysical tests proved ability to generate useful perceptions, with a Just Noticeable Difference characterised by a Weber constant of 0.15. The system was made of off-the-shelf materials and components, without any special manufacturing process, and is fully disclosed, providing schematics and lists of components. This was aimed at making it easily and freely usable, so as to turn tactile displays of softness on fingertips into a technology 'at fingertips'.


Interpretation of ground-level ozone episodes with atmospheric stability index measurement.
This paper presents a novel approach to interpret ground-level O(3) with the measured atmospheric stability index (ASI). O(3) concentrations were monitored by automatic analysers at three types of stations: traffic site, residential site and regional background site in 2005, and the ASI was simultaneously measured by observing radon and its short-lived decay products. The observed results showed a clear annual variation of O(3) concentrations with a maximum in spring, relatively high at the regional background site over 120 ppb, and lower at the residential and traffic sites at about 70 ppb. ASI gives information about the dilution properties of the lower boundary layer and allows to highlight the relevant role of the dilution factor in determining atmospheric pollution events. We demonstrated the analysis of O(3) night peak episodes with vertical wind and ASI. With the advantage of ASI and vertical wind profiles, it was possible to isolate particular photochemical pollution phenomena of O(3) peaks from the free troposphere reservoir or formed by local reactions. This shows that the index constitutes a powerful and valuable tool for describing O(3) night-peak episodes at background station.


The perspectives of Australian midwifery academics on barriers and enablers for simulation in midwifery education in Australia: a focus group study.
to describe Australian midwifery academics' perceptions of the current barriers and enablers for simulation in midwifery education in Australia and the potential and resources required for simulation to be increased. a series of 11 focus groups/interviews were held in all states and territories of Australia with 46 participating academics nominated by their heads of discipline from universities across the country. three themes were identified relating to barriers to the extension of the use of simulated learning environments (SLEs) ('there are things that you can't simulate'; 'not having the appropriate resources'; and professional accreditation requirements) and three themes were identified to facilitate SLE use ('for the bits that you're not likely to see very often in clinical'; ['for students] to figure something out before [they] get to go out there and do it on the real person'; and good resources and support). although barriers exist to the adoption and spread of simulated learning in midwifery, there is a long history of simulation and a great willingness to enhance its use among midwifery academics in Australia. while some aspects of midwifery practice may be impossible to simulate, more collaboration and sharing in the development and use of simulation scenarios, equipment, space and other physical and personnel resources would make the uptake of simulation in midwifery education more widespread. Students would therefore be exposed to the best available preparation for clinical practice contributing to the safety and quality of midwifery care.


Synthesis of type VI collagen by cultured glomerular cells and comparison of its regulation by glucose and other factors with that of type IV collagen.
Homogeneous cultures of calf glomerular mesangial and endothelial cells were found to be active in the synthesis of type VI as well as type IV collagen in contrast to the epithelial cells that were devoted primarily to the production of the latter collagen. Studies with rat mesangial cells indicated that they responded to high glucose (20 mM) in the medium by a significant (P < 0.001) increase in type VI collagen synthesis as measured by the production of the protein and its mRNA level, both of which were closely correlated to each other and to glucose consumption. Similar observations were made with type IV collagen, but the enhanced formation of this protein was not as rapidly apparent as that of type VI and, moreover, could not be as readily reversed on restoration of the glucose to a physiological level (5 mM). Evaluation of a number of other agents indicated that although mannitol had no effect, L-glucose and NaCl significantly stimulated synthesis of both type VI and IV collagens and glucose consumption. Insulin-like growth factor I and aldosterone, on the other hand, also increased glucose consumption but brought about an enhancement of only type IV collagen production, suggesting that the two collagens are independently regulated. This possibility was supported by our observation that pyruvate, which was actively taken up by the cells, selectively stimulated type IV collagen production.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduced activity of alkaline phosphatase due to host-guest interactions with humic superstructures.
Nuclear Magnetic Resonance (NMR) spectroscopy was applied to directly study the interactions between the alkaline phosphatase enzyme (AP) and two different humic acids from a volcanic soil (HA-V) and a Lignite deposit (HA-L). Addition of humic matter to enzyme solutions caused signals broadening in (1)H-NMR spectra, and progressive decrease and increase of enzyme relaxation (T1 and T2) and correlation (τC) times, respectively. Spectroscopic changes were explained with formation of ever larger weakly-bound humic-enzyme complexes, whose translational and rotational motion was increasingly restricted. NMR diffusion experiments also showed that the AP diffusive properties were progressively reduced with formation of large humic-enzyme complexes. The more hydrophobic HA-L affected spectral changes more than the more hydrophilic HA-V. (1)H-NMR spectra also showed the effect of progressively greater humic-enzyme complexes on the hydrolysis of an enzyme substrate, the 4-nitrophenyl phosphate disodium salt hexahydrate (p-NPP). While AP catalysis concomitantly decreased NMR signals of p-NPP and increased those of nitrophenol, addition of humic matter progressively and significantly slowed down the rate of change for these signals. In agreement with the observed spectral changes, the AP catalytic activity was more largely inhibited by HA-L than by HA-V. Contrary to previous studies, in which humic-enzyme interactions were only indirectly assumed from changes in spectrophotometric behavior of enzyme substrates, the direct measurements of AP behavior by NMR spectroscopy indicated that humic materials formed weakly-bound host-guest complexes with alkaline phosphatase, and the enzyme catalytic activity was thereby significantly inhibited. These results suggest that the role of extracellular enzymes in soils may be considerably reduced when they come in contact with organic matter dissolved in the soil solution.


Effects of acute and chronic hypoxia on the radiosensitivity of gastric and esophageal cancer cells.
The aim of this study was to examine the effects of hypoxia on radiosensitivity and to analyze the mechanisms responsible for radiation resistance in gastric and esophageal cancer. A gastric cancer cell line, OCUM-12, and an esophageal cancer cell line, TE-6, were used. The effects of hypoxia with irradiation on the growth-activity, cell cycle distribution, and gene expression were examined. Both acute and chronic hypoxia decreased radiosensitivity of cancer cells. The radiosensitivity of chronic hypoxic cells was significantly enhanced by reoxygenation. Acute and chronic all hypoxia reduced the percentage of cells in the G(2)/M and S phases, respectively. In acute hypoxia, the mRNA expression of BRCA1 and BRCA2 was reduced in cancer cells. Reoxygenation increased the expression of BRCA1 and BRCA2. Hypoxia is associated with radiation resistance. Therefore, reoxygenation may enhance the radiosensitivity of hypoxic cells. BRCA1 and BRCA2 may be associated with factors for radiation resistance by regulation of cell cycle progression.


Central corneal thickness in patients with congenital aniridia.
To compare the mean central corneal thickness (CCT) in patients with congenital aniridia to that of a group of age-matched control subjects. The findings of specular and confocal microscopy in a patient with aniridia are discussed. The mean values of five consecutive pachymetry measurements of patients with aniridia and control subjects were used for analysis. Statistical analysis was performed with a Mann-Whitney rank sum test. Specular microscopy was performed on one patient with aniridia using a Konan Specular Microscope Noncon ROBO CA (Hyogo, Japan). Confocal microscopy through focusing was performed with the Tandem Scanning Confocal Microscope (Reston, VA). Mean CCT measured 691.8 +/- 75.4 mum for patients with aniridia (16 eyes of 10 patients) and 548.2 +/- 21.2 mum for control subjects (P < 0.001). Specular microscopy in a patient with aniridia showed normal endothelial cell counts and structure. Confocal microscopy through focusing of this patient showed normal-appearing keratocytes and a thick corneal stroma. Patients with congenital aniridia have significantly thicker corneas than do age-matched control subjects. This difference can have important implications for the treatment of those patients who develop secondary glaucoma. The increased CCT in patients with aniridia is not a result of endothelial dysfunction but appears to be the result of the production of a thickened but otherwise healthy cornea by the mutated PAX6 gene.


Sequential bypass using the right gastroepiploic artery for coronary artery bypass grafting.
Since 1989, we have applied the right gastroepiploic artery (RGEA) as a third arterial conduit for coronary artery bypass grafting (CABG) and started to use sequential RGEA in 1992. We evaluated the feasibility and efficacy of sequential RGEA grafting in CABG. From December 1990 to January 2000, 46 patients underwent CABG with sequential RGEA. There were 42 male and 4 female patients with a mean age of 59 +/- 8.1 years. Mean postoperative follow-up period was 70 months. The mean number of anastomoses was 3.7 per patient. Mean luminal diameter of the RGEA was 2.2 +/- 0.4 mm by preoperative angiography and 2.3 +/- 0.6 mm by intraoperative measurement. Patency of the sequential RGEA was 92%; proximal anastomosis 100%, distal anastomosis 86% (p = 0.01). The 5-year actuarial survival and cardiac event-free rate were 91% and 93%, respectively. Sequential bypass using the RGEA is feasible, with excellent early and long-term results. The indication for sequential RGEA, however, needs careful anatomical consideration of both the luminal diameter of the RGEA and proximal stenosis of the target coronary arteries.


Interaction of [3H]dipyridamole with the nucleoside transporters of human erythrocytes and cultured animal cells.
Equilibrium binding of [3H]dipyridamole identified high-affinity (Kd approximately 10 nM) binding sites on human erythrocytes (approximately 5 X 10(5) sites/cell) and on HeLa cells (approximately 5 X 10(6) sites/cell). The equilibration of dipyridamole with these sites on human erythrocytes was compatible with a second-order process which proceeded at 22 degrees C with a rate constant of about 6 X 10(6) M-1 sec-1. Binding of dipyridamole to these sites correlated kinetically with the inhibition of the equilibrium exchange of 500 microM uridine in these cells and was inhibited in a concentration-dependent manner by nucleosides and other inhibitors of nucleoside transport, such as nitrobenzylthioinosine, dilazep and lidoflazine, but not by hypoxanthine, which is not a substrate for the nucleoside transporter of human erythrocytes. The results indicate that the substrate binding site of the transporter is part of the high-affinity dipyridamole binding site. Bound [3H]dipyridamole became displaced from these sites on human erythrocytes by incubation with an excess of unlabeled dipyridamole or high concentrations of nucleosides and inhibitors of nucleoside transport, but neither by hypoxanthine nor sugars. Dissociation of [3H]dipyridamole behaved as a simple first-order process, but the rate constant was about one order of magnitude lower (about 3 X 10(-3) sec-1) than anticipated for typical ligand-protein binding on the basis of the measured association rate and equilibrium constants. The reason for this discrepancy has not been resolved. No high-affinity dipyridamole binding sites were detected on Novikoff rat hepatoma cells, P388, L1210 and S49 mouse leukemia cells or Chinese hamster ovary cells, and their absence correlated with a greater resistance of nucleoside transport in these cells to inhibition by dipyridamole. All cells expressed considerable low affinity (Kd greater than 0.5 microM) and nonspecific binding of dipyridamole.


Glycan deletions in the HIV-1 gp120 V1/V2 domain compromise viral infectivity, sensitize the mutant virus strains to carbohydrate-binding agents and represent a specific target for therapeutic intervention.
Carbohydrate-binding agents (CBAs), such as the mannose-specific Hippeastrum hybrid agglutinin (HHA) and the GlcNAc-specific Urtica dioica agglutinin (UDA), frequently select for glycan deletions in all different domains of HIV-1 gp120, except in the V1/V2 domain. To reveal the underlying mechanisms, a broad variety of 31 different virus strains containing one or several N-glycan deletions in V1/V2 of the gp120 of the X4-tropic HIV-1(NL4.3) were constructed by chimeric virus technology. No co-receptor switch to CCR5 was observed for any of the replication-competent mutant virus strains. With a few exceptions, the more glycans were deleted in the gp120 V1/V2 domain, the more the replication capacity of the mutant viruses became compromised. None of the mutant virus strains showed a markedly decreased sensitivity to the inhibitory activity of HHA and UDA. Instead, an up to 2- to 10-fold higher sensitivity to the inhibitory activity of these CBAs was observed. Our data may provide an explanation why glycan deletions in the gp120 V1/V2 domain rarely occur under CBA pressure and confirm the important functional role of the glycans in the HIV-1 gp120 V1/V2 domain. The gp120 V1/V2 loop glycans of HIV-1 should therefore be considered as a hot spot and novel target for specific therapeutic drug intervention.


Non-canonical D-xylose and L-arabinose metabolism via D-arabitol in the oleaginous yeast Rhodosporidium toruloides.
R. toruloides is an oleaginous yeast, with diverse metabolic capacities and high tolerance for inhibitory compounds abundant in plant biomass hydrolysates. While R. toruloides grows on several pentose sugars and alcohols, further engineering of the native pathway is required for efficient conversion of biomass-derived sugars to higher value bioproducts. A previous high-throughput study inferred that R. toruloides possesses a non-canonical L-arabinose and D-xylose metabolism proceeding through D-arabitol and D-ribulose. In this study, we present a combination of genetic and metabolite data that refine and extend that model. Chiral separations definitively illustrate that D-arabitol is the enantiomer that accumulates under pentose metabolism. Deletion of putative D-arabitol-2-dehydrogenase (RTO4_9990) results in > 75% conversion of D-xylose to D-arabitol, and is growth-complemented on pentoses by heterologous xylulose kinase expression. Deletion of putative D-ribulose kinase (RTO4_14368) arrests all growth on any pentose tested. Analysis of several pentose dehydrogenase mutants elucidates a complex pathway with multiple enzymes mediating multiple different reactions in differing combinations, from which we also inferred a putative L-ribulose utilization pathway. Our results suggest that we have identified enzymes responsible for the majority of pathway flux, with additional unknown enzymes providing accessory activity at multiple steps. Further biochemical characterization of the enzymes described here will enable a more complete and quantitative understanding of R. toruloides pentose metabolism. These findings add to a growing understanding of the diversity and complexity of microbial pentose metabolism.


Pipeline for previously stented basilar trunk aneurysm: a case focusing on how the pipeline should be deployed.
Recurrent, previously stented basilar trunk aneurysms pose significant challenges to either microsurgical clipping or traditional endovascular treatment. We here presented an intriguing case that was successfully treated by the pipeline embolization device (PED; ev3/Covidien Neurovascular, Irvine, California, USA). A 62-year-old male found a recurrent aneurysm, which had been treated with coiling and stent-assisted coiling before. The patient came to our center seeking for a third treatment. In our center, a single PED and additional coils were used to treat this refractory aneurysm. The whole length of the PED was delicately implanted in the previous Enterprise stent (Cordis Corporation, Miami FL, USA), which resembled the double-layer flow diverter FRED (Microvention, Tustin, California, USA). The inflow zone of the aneurysmal sac was further coiled considering that this aneurysm had ruptured. No procedure-related complications occurred. Follow-up angiogram at 6 months indicated that the intractable aneurysm was completely occluded and the patient was free from any neurologic deficit. This is a case that adds knowledge to improve the poor performance of flow diverters in previously stented aneurysms. However, future studies with larger group of patients are needed to further test the safety and efficacy of this technique.


Percutaneous Endoscopic Lumbar Discectomy Versus Posterior Open Lumbar Microdiscectomy for the Treatment of Symptomatic Lumbar Disc Herniation: A Systemic Review and Meta-Analysis.
The purpose of this systematic review and meta-analysis was to compare the clinical efficacy between percutaneous endoscopic lumbar discectomy (PELD) versus posterior open lumbar microdiscectomy (OLMD) for the treatment of symptomatic lumbar disc herniation. We performed a comprehensive retrieval of related studies in 4 electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library). Randomized or nonrandomized controlled trials reported from January 1990 to December 2017 that compared PELD versus OLMD for the treatment of symptomatic lumbar disc herniation were acquired. The quality of randomized controlled trials was evaluated by the criteria of the Cochrane Back Review Group, and the quality of cohort studies was assessed according to the Newcastle-Ottawa Scale. The primary outcome measurements included preoperative and postoperative visual analog scale (VAS) score of sciatica; the Oswestry Disability Index (ODI) before and after surgery; the Excellent and Good outcome rate based on Macnab criteria. The secondary outcome measurements included the incidence of complication, residual disk, recurrence, and reoperation; operation time; hospital stay; and time to return to work. Two authors independently extracted data and assessed each study for quality. Nine studies with 1585 patients were included in our meta-analysis. Two were randomized controlled trials and the remaining 7 were retrospective cohort studies. The forest plots showed that no statistically significant difference was observed between the 2 groups in terms of preoperative and postoperative VAS score of sciatica, ODI before and after surgery, the Excellent and Good outcome rate, the complication rate, and the incidence of recurrence and reoperation. However, the PELD group had a higher incidence of residual disk or incomplete decompression than did the OLMD group. In addition, no significant difference was detected in the operation time between the 2 groups, but the PELD group was associated with shorter hospital stay and time of return to work. Based on the present meta-analysis, no significant difference existed in VAS and ODI scores between the 2 surgical procedures, and they were also similar in terms of operation time, complication rate, and incidence of recurrence and reoperation, but PELD showed shorter hospital stay and time of return to work. Thus, under the premise of careful manipulation and complete decompression, we consider that PELD is a relatively more minimally invasive technique, which could be an alternative to OLMD.


Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors.
A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC(50)=0.24μM for EGFR and IC(50)=1.07μM for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC(50) value of 0.30, 0.54, and 0.70μM, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent.


Comparison of metacarpal plating methods.
Most metacarpal fractures are stable and can be treated with nonsurgical stabilization. However, some metacarpal fractures are treated with open reduction and internal fixation because of an open fracture, instability, or multiple fractures. Newer plate designs have emerged that allow a shorter plate and screw construct. We sought to determine the relative strength of 3 different methods of metacarpal plating for unstable fractures. We tested our hypothesis in a transverse metacarpal fracture model using fourth-generation, biomechanical testing grade composite sawbones (Sawbones; Pacific Research Laboratories, Vashon, WA). The metacarpals were divided into 3 groups of 15 bones. Group 1 was plated with a standard 6-hole, 2.3-mm plate with 6 nonlocking bicortical screws in standard AO fashion. Group 2 was plated with a 6-hole, double-row, 3-dimensional (3D) plate with 3 nonlocking screws on either side of the fracture aiming for convergence of the screws. Group 3 was plated with a 2.4-mm plate using 6 nonlocking screws and standard AO technique. The metacarpals were then tested to failure in cantilever bending mode. All constructs broke through the bone. No plate failure or screw pullout was seen. Group 1 had a load to failure of 264 N +/- 14. Group 2 had a load to failure of 302 N +/- 17. Group 3 had a load to failure of 274 N +/- 20. The load to failure was highest in group 2 (3D plate). All differences were statistically significant. All 3 methods produced a strong construct. The load to failure was highest in group 2 (3D plate). Double-row plates with converging screws provide adequate or superior strength of fixation when compared with standard plate constructs.


Fluoroscopy Assisted Scoring of Myocardial Hypoperfusion (FLASH) ratio as a novel predictor of mortality after primary PCI in STEMI patients.
The aim of this study was to investigate whether Fluoroscopy Assisted Scoring of Myocardial Hypoperfusion (FLASH) enabled a more accurate assessment of coronary blood flow and prediction of cardiac mortality after primary PCI (pPCI), than the presently used angiographic scores of reperfusion. We included 453 STEMI patients who received pPCI at our hospital. Using the novel FLASH algorithm, based on contrast passage time and quantitative coronary analysis, FLASH flow was measured after pPCI and was used to calculate FLASH ratio of culprit and reference artery. In 28 of the 453 patients, FLASH flow was compared to Doppler-derived-flow. FLASH flow had a good correlation with Doppler derived flow (Pearson's R=0.65, p<0.001) and had a high inter-observer agreement (ICC=0.83). FLASH flow was significantly lower in patients that died of cardiac death within six months (25.9±17.7 ml/min vs. 38.2±18.8 ml/min, p=0.004). FLASH ratio had a high accuracy of predicting cardiac mortality with a significant higher area under the curve as compared with CTFC and QuBe (p=0.041 and p=0.008). FLASH ratio was an independent predictor of mortality at 6 months (HR=0.98 per 1% increase, p=0.014). FLASH is a simple non-invasive method to estimate coronary blood flow and predict mortality directly following pPCI in STEMI patients, with a higher accuracy compared to the presently used angiographic scores.


Fate of multipotent neural precursor cells transplanted into mouse retina selectively depleted of retinal ganglion cells.
In some parts of the CNS, depletion of a particular class of neuron might induce changes in the microenvironment that influence the differentiation of newly grafted neural precursor cells. This hypothesis was tested in the retina by inducing apoptotic retinal ganglion cell (RGC) death in neonatal and adult female mice and examining whether intravitreally grafted male neural precursor cells (C17.2), a neural stem cell (NSC)-like clonal line, become incorporated into these selectively depleted retinae. In neonates, rapid RGC death was induced by removal of the contralateral superior colliculus (SC), in adults, delayed RGC death was induced by unilateral optic nerve (ON) transection. Cells were injected intravitreally 6-48 h after SC ablation (neonates) or 0-7 days after ON injury (adults). Cells were also injected into non-RGC depleted neonatal and adult retinae. At 4 or 8 weeks, transplanted cells were identified using a Y-chromosome marker and in situ hybridisation or by their expression of the lacZ reporter gene product Escherichia coli beta-galactosidase (beta-gal). No C17.2 cells were identified in axotomised adult-injected eyes undergoing delayed RGC apoptosis (n = 16). Donor cells were however stably integrated within the retina in 29% (15/55) of mice that received C17.2 cell injections 24 h after neonatal SC ablation; 6-31% of surviving cells were found in the RGC layer (GCL). These NSC-like cells were also present in intact retinae, but on average, there were fewer cells in GCL. In SC-ablated mice, most grafted cells did not express retinal-specific markers, although occasional donor cells in the GCL were immunopositive for beta-III tubulin, a protein highly expressed by, but not specific to, developing RGCs. Targeted rapid RGC depletion thus increased cell incorporation into the GCL, but grafted C17.2 cells did not appear to differentiate into an RGC phenotype.


Early echocardiography abnormalities in obese children and adolescent and reversibility of these abnormalities after significant weight reduction.
Obesity is becoming an epidemic threat for the individual and society. The increasing prevalence of overweight children and adolescents is likely to have a great impact on the future cardiovascular health of these subjects. Obesity is a strong risk factor for cardiovascular morbidity and mortality. Cardiac abnormalities of obese children and adolescents include the echocardiographically revealed early and preclinical LV or septal hypertrophy, and left or right ventricular dysfunction. Most of these abnormalities, which are usually more pronounced in patients with morbid obesity, can be partially reversed after weight reduction. Evaluate early echocardiography changes in obese children and whether these cardiac abnormalities reverse with significant weight reduction in children and adolescents or not. We started this study by 50 obese children and adolescents and 30 non obese controls matched for age and sex. BMI was calculated. Complete echocardiographic study was performed on each patient and control subject. Hematological and biochemical variables were determined in the obese subjects from fasting blood samples and included glucose, total cholesterol, triglycerides (TG), HDL cholesterol and LDL cholesterol. All our patients' strict dietetic regime with exercises for 6 months. After 6 months full examination, including all measurements and echocardiography and laboratory investigations were done again. Obese children has abnormalities of left ventricle structure and function (consisting of increased left ventricular wall dimensions and mass and alteration of diastolic function) that can be detected by echocardiography. Furthermore, (parameters of lipid metabolism) were found to be independent predictors of adverse LV remodeling and of diastolic dysfunction. As well as this study provides evidence that abnormalities of left ventricular wall dimension and mass in obese children and adolescents can improve with significant weight reduction. This study has demonstrated that young, obese children and adolescents have early significant changes in left ventricular wall dimensions and early diastolic filling compared with non obese and this changes are reversible with weight reduction.


Molecular epidemiology of bovine toroviruses circulating in South Korea.
The prevalence of the bovine torovirus (BToV) and its genetic characterization have been reported in North America, Europe and Japan. Therefore, this study examined the prevalence and genetic diversity of the BToV in a total of 645 diarrheic fecal samples from 629 Korean native beef calf herds using RT-PCR and nested PCR with the primer pairs specific to a part of the BToV membrane (M) gene. Overall, 19 (2.9%) out of 645 diarrheic samples from 19 herds (6.9%) tested positive for BToVs by either RT-PCR or nested PCR. A comparison of the nucleotide (nt) and amino acid (aa) sequences of a part of the BToV M gene (409bp) among the BToVs showed the Korean BToVs to have comparatively higher sequence homology to the Japanese and Dutch BToVs than to the American and Italian BToVs. Generally, the Korean BToV strains clustered with the Japanese and Dutch BToV strains. However, the American and Italian BToV strains clustered on a separate major branch, suggesting that these are more distantly related to other known BToV strains. These results suggest that the BToV infections are sporadic in diarrheic calves in South Korea, and the Korean BToV strains are more closely related to the Japanese and Dutch BToVs than to the American and Italian BToVs.


Membrane lipids of hepatocytes, Kupffer cells and endothelial cells.
The membrane lipid composition of isolated hepatocytes, Kupffer cells and endothelial cells was determined. The hepatocytes are characterized by a lower quantity of gangliosides, cholesterol, sphingomyelin and a reduced cholesterol/phospholipid molar ratio when compared to the two other liver cell types. The main gangliosides of Kupffer and endothelial cells are the GM3 species, and those of hepatocytes are of the polysialogangliosides species.


In situ readout of DNA barcodes and single base edits facilitated by in vitro transcription.
Molecular barcoding technologies that uniquely identify single cells are hampered by limitations in barcode measurement. Readout by sequencing does not preserve the spatial organization of cells in tissues, whereas imaging methods preserve spatial structure but are less sensitive to barcode sequence. Here we introduce a system for image-based readout of short (20-base-pair) DNA barcodes. In this system, called Zombie, phage RNA polymerases transcribe engineered barcodes in fixed cells. The resulting RNA is subsequently detected by fluorescent in situ hybridization. Using competing match and mismatch probes, Zombie can accurately discriminate single-nucleotide differences in the barcodes. This method allows in situ readout of dense combinatorial barcode libraries and single-base mutations produced by CRISPR base editors without requiring barcode expression in live cells. Zombie functions across diverse contexts, including cell culture, chick embryos and adult mouse brain tissue. The ability to sensitively read out compact and diverse DNA barcodes by imaging will facilitate a broad range of barcoding and genomic recording strategies.


An examination of knowledge, attitudes and practices related to HIV/AIDS prevention in Zimbabwean university students: comparing intervention program participants and non-participants.
This study represents a comprehensive assessment of differences between participants in an HIV/AIDS prevention program (SHAPE: Sustainability, Hope, Action, Prevention, Education) and non-participants in knowledge, attitudes and practices with a focus on cultural, sociological and economic variables. We developed an eight-page questionnaire that was administered to 933 randomly selected students at the University of Zimbabwe. Survey items addressed sexual decision-making, condom use, limiting sexual partners, cultural power dynamics and access to HIV testing. Results show participants are statistically more likely to report being sexually abstinent, and understand the prevention benefits of condom use. SHAPE members had fewer sexual partners in the previous year than non-SHAPE members (1.4 vs. 2.2). SHAPE members were significantly more likely (67%) than non-SHAPE respondents (48%) to indicate that they knew their HIV sero-status and to state that they knew their status because they had been tested (85% vs. 71%). Though we found differences between the groups suggesting that program participation increases awareness concerning gender equity, there continue to be many intractable cultural attitudes in this age group. Findings suggest that the attitudes and practices of young men and women are changing, but that progress in some areas does not assure progress in all areas.


Repetitive nerve stimulation cutoff values for the diagnosis of myasthenia gravis.
Repetitive nerve stimulation (RNS) showing ≥ 10% decrement is considered the cutoff for myasthenia gravis (MG), but this has never been validated. The objective of this study was to find an optimal validated cutoff value for decrement on RNS. We performed retrospective chart review of patients who had electrophysiological assessment for possible MG from 2013 to 2015. A total of 122 patients with MG and 182 controls were identified. RNS sensitivities for generalized and ocular MG using the traditional ≥10% cutoff value were 46% and 15%, respectively, for frontalis recordings, and 35% and 19%, respectively, for nasalis recordings. Using a decrement cutoff value of 7% for frontalis and 8% for nasalis increased the sensitivities by 6-11%, with specificities of 95-96%. For RNS in facial muscles, we suggest a cutoff value of 7-8%, which increases test sensitivity by 6-11%, while preserving high specificity for the diagnosis of MG. Muscle Nerve, 2016 Muscle Nerve 55: 166-170, 2017.


The hydraulic permeability of blood clots as a function of fibrin and platelet density.
Interstitial fluid flow within blood clots is a biophysical mechanism that regulates clot growth and dissolution. Assuming that a clot can be modeled as a porous medium, the physical property that dictates interstitial fluid flow is the hydraulic permeability. The objective of this study was to bound the possible values of the hydraulic permeability in clots formed in vivo and present relationships that can be used to estimate clot permeability as a function of composition. A series of clots with known densities of fibrin and platelets, the two major components of a clot, were formed under static conditions. The permeability was calculated by measuring the interstitial fluid velocity through the clots at a constant pressure gradient. Fibrin gels formed with a fiber volume fraction of 0.02-0.54 had permeabilities of 1.2 × 10(-1)-1.5 × 10(-4)μm(2). Platelet-rich clots with a platelet volume fraction of 0.01-0.61 and a fibrin volume fraction of 0.03 had permeabilities over a range of 1.1 × 10(-2)-1.5 × 10(-5)μm(2). The permeability of fibrin gels and of clots with platelet volume fraction of <0.2 were modeled as an array of disordered cylinders with uniform diameters. Clots with a platelet volume fraction of >0.2 were modeled as a Brinkman medium of coarse solids (platelets) embedded in a mesh of fine fibers (fibrin). Our data suggest that the permeability of clots formed in vivo can vary by up to five orders of magnitude, with pore sizes that range from 4 to 350 nm. These findings have important implications for the transport of coagulation zymogens/enzymes in the interstitial spaces during clot formation, as well as the design of fibrinolytic drug delivery strategies.


Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial.
The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938).


In vivo allograft rejection in a bony fish Dicentrarchus labrax (L.): characterisation of effector lymphocytes.
Lymphoid cell subpopulations involved in allograft rejection in the teleost Dicentrarchus labrax were characterised at the ultrastructural level and quantified by using monoclonal antibodies against T- and B-lymphocytes. T-cells positive for T-cell receptor beta-chain (TcR beta) were detected by reverse transcription/polymerase chain reaction (RT-PCR) and in situ hybridisation by using RNA probes for TcR beta. Flow cytometry detected a similar percentage of T- and B-lymphocytes (around 17%) in the leucocyte-enriched fraction from allografts. Two different types of T-lymphocytes (DLT 15-immunoreactive) infiltrating the allografts were identified by cytomorphology: small cells with high nuclear/cytoplasmic ratio and cells with a higher cytoplasmic content. RT-PCR revealed a single band (513 bp) corresponding to the TcR beta. In situ hybridisation showed that TcR beta-positive cells in the grafted muscle fibres were less numerous compared with DLT 15-positive cells, as evidenced in parallel sections, suggesting that cytotoxic cells might express different TcR phenotypes. DLIg 3-immunoreactive Ig-producing lymphocytes had: 1) a high nuclear/cytoplasmic ratio or 2) a larger size similar to that of pre-plasma cells (plasma cells lacked any membrane labelling).


Delayed spinal infection after laminectomy in a patient with rheumatoid arthritis interruptedly exposed to anti-tumor necrosis factor alpha agents.
We report a case of spondylodiscitis caused by Staphylococcus aureus 8 months after laminectomy of the lumbar spine, occurring in a rheumatoid arthritis (RA) patient interruptedly treated with anti-tumor necrosis alpha (TNFalpha) agents. The patient had suffered from seropositive RA for 2 years. An intravenous infusion (200 mg) of infliximab, a chimeric antibody against human TNFalpha, was introduced; however, due to Pneumocystis jiroveci pneumonia, this therapy was withdrawn. Four months later, the patient underwent an L3-L4 and L4-L5 laminectomy for spinal stenosis. Two months after surgery, we started treatment with 25 mg of etanercept, a soluble humanized TNF receptor dimer, subcutaneously twice a week. At that time, wound healing was satisfactory and no evidence of infection was obtained. Eight months after surgery, septic spondylodiscitis of the lumbar spine occurred. To the best of our knowledge, this is the first case in the literature to show a delayed type of postoperative infection as a complication of non-instrumented orthopedic surgical procedures. Despite interruption of anti-TNFalpha therapy before surgery, patients may remain at risk of developing postoperative infections.


Construction of a 3D Model of Epitympanic Folds and Spaces.
This article reports a technique for making a 3 dimensional(3D) model of the epitympanic folds and spaces in the middle ear. It is intended as a teaching model for both undergraduate and post-graduate medical students.


Papillary renal carcinoma (clear cell type) arising in the escretory urothelial district: a very unusual feature.
A case of renal cell carcinoma, clear cell type, originating from the calyceal renal mucosa, is described.


Impact of the number of veins repaired in short-term digital replantation survival rate.
Venous congestion/insufficiency plays a major role in failure of finger replantation. Despite acceptable salvage rates with postoperative anticoagulation or leeching, operative technique remains the most important predictor of success. However, there are no indications in the literature on the benefit of anastomosing single versus multiple veins. A retrospective review of finger amputations from 2011 to 2013 was conducted. The analyzed endpoint was the finger survival rate at discharge depending on the number of veins repaired: multiple veins (group 1), only one vein (group 2), or no veins (group 3). Proportions were compared using v2 tests/Fisher's exact tests; p-value <0.05 was considered significant. Seventy-two patients with complete digital amputation were operated including 101 fingers. Twenty-seven fingers (26.7%) failed before hospital discharge, with 78% of failures due to venous complications versus 22% with an arterial etiology. Group 2 had 15 replantation failures due to venous causes as opposed to only one from group 1, representing a 1.27-fold (95% confidence interval (CI): 0.99, 1.34) increased relative risk of failure (p = 0.032). Similarly, five fingers from group 3 suffered venous complications, resulting in a 1.49-fold (95% CI: 1.02, 1.73) increased likelihood of failure in comparison to group 1 (p = 0.008). No significant difference was observed between having only one vein repaired versus none (RR: 1.1792, 95% CI: 0.83, 2.10, p = 0.502). Efforts toward favoring two-vein repair lead to better survival of the replanted fingers. More cases need to be analyzed before formulating conclusions on specific levels of amputation with regard to venous anastomoses.


Synthetic peptide inhibitors of complement serine proteases--II. Effects on hemolytic activity and production of C3a and C4a.
Synthetic peptides based on the amino acid sequence at the site of cleavage of C3 by classical and alternative pathway convertases were found to be poor inhibitors of hemolysis except at concns of 1 mM and higher. Synthetic peptides of a second type, based on the C-terminal sequence of antithrombin III, were more effective; the best among them caused significant inhibition of hemolysis at a concn of 5 microM. A hybrid peptide composed of the sequence at the site of cleavage of C4 by C1s attached to an antithrombin III sequence was selective, inhibiting the classical pathway with no effect on the alternative pathway at a concentration of 25 microM. Several of the antithrombin III peptides that inhibited hemolysis did not inhibit C4 activation by the classical pathway or activation of C3 by the classical and alternative pathways suggesting that these peptides affect hemolysis by inhibiting enzymes other than C1s and C4b2a of the classical pathway and C3bBb of the alternative pathway.


The association of human c-Ha-ras sequences with chromatin and nuclear proteins.
As a step towards the understanding of possible relationship between chromatin organization and regulation of the oncogene expression, we have investigated the chromatin structure of one of the more frequently activated oncogenes, c-Ha-ras, in HeLa-S3 cells. This was accomplished by isolation of the chromatin fractions (soluble and insoluble) after micrococcal nuclease digestion of purified nuclei and probing for the distribution of ras sequences. The polynucleosomal fraction was further resolved by sucrose gradient sedimentation. Southern-blot hybridization of the DNA isolated from various fractions yielded following results: (1) c-Ha-ras sequences segregated predominantly in the lysate fraction. (2) Unlike the B-globin (transcriptionally inactive) sequences, ras-H associated chromatin lacked typical nucleosomal packaging. Furthermore, since post-translational modifications of nuclear proteins have been suggested to modulate the nucleosome structure during DNA transcription and replication, ras sequences, in polynucleosomes immunofractionated on anti-poly (ADP-Ribose) Sepharose were also examined. The data suggested that the major class of this oncogene sequence exists in chromatin more distal to the sites of this particular chromatin modification.


Do we still need a diverticuloscope for the flexible endoscopic septotomy of Zenker's diverticulum?
Zenker's diverticulum (ZD) is the most common type of diverticulum in the esophagus. The endoscopic septotomy of the diverticular wall has become a widely accepted treatment modality, but the recurrence rate is unclear. Our aim was to assess short-term and long-term success rates after flexible endoscopic septotomy for the treatment of ZD. All consecutive patients treated at our department for a ZD between November 2014 and September 2018 were included. Endoscopic septotomy was conducted using a diverticuloscope or a distal attachment cap. Data were retrospectively analyzed from a prospectively collected database. We collected data concerning patients, endoscopic procedures, and short-term clinical outcomes. All patients were reached by phone between October and December 2018 to assess long-term results. Seventy-seven patients were referred to our department for a ZD. Sixty patients were treated using a diverticuloscope and 17 patients with a distal attachment cap. For all 77 patients, the myotomy was technically successful. Three patients treated with a diverticuloscope reported complications. Initial treatment success was 93%. After a mean (±SEM) follow up of 23 ± 2 months, 66% of patients had persistent clinical remission. The rate of long-term treatment success was 72% in treatment-naïve and 50% in previously treated patients (P = 0.13). Treatment success was 68% in patients treated with the diverticuloscope versus 60% in the group treated with a cap (P = 0.75). The flexible endoscopic septotomy for the treatment of ZD is a safe and effective treatment of ZD, with or without a diverticuloscope.


Oligonuclear polypyridylruthenium(II) complexes: selectivity between bacteria and eukaryotic cells.
The objectives of this study were to: (i) determine the in vitro activities of a series of di-, tri- and tetra-nuclear ruthenium complexes (Rubbn, Rubbn-tri and Rubbn-tetra) against a range of Gram-positive and -negative bacteria and compare the antimicrobial activities with the corresponding toxicities against eukaryotic cells; and (ii) compare MIC values with achievable in vivo serum concentrations for the least toxic ruthenium complex. The in vitro activities were determined by MIC assays and time-kill curve experiments, while the toxicities of the ruthenium complexes were determined using the Alamar blue cytotoxicity assay. A preliminary pharmacokinetic study was undertaken to determine the Rubb12 serum concentration in mice as a function of time after administration. Rubb12, Rubb12-tri and Rubb12-tetra are highly active, with MIC values of 1-2 mg/L (0.5-1.5 μM) for a range of Gram-positive strains, but showed variable activities against a panel of Gram-negative bacteria. Time-kill experiments indicated that Rubb12, Rubb12-tri and Rubb12-tetra are bactericidal and kill bacteria within 3-8 h. The di-, tri- and tetra-nuclear complexes were ∼50 times more toxic to Gram-positive bacteria and 25 times more toxic to Gram-negative strains, classified as susceptible, than to liver and kidney cells. Preliminary pharmacokinetic experiments established that serum concentrations higher than MIC values can be obtained for Rubb12 with an administered dose of 32 mg/kg. The ruthenium complexes, particularly Rubb12, have potential as new antimicrobial agents. The structure of the dinuclear ruthenium complex can be readily further modified in order to increase the selectivity for bacteria over eukaryotic cells.


Large hemangiopericytoma associated with arteriovenous malformations and dural arteriovenous fistulae.
Hemangiopericytomas are rare vascular tumors of the central nervous system. Although hemangiopericytomas have been associated with other vascular malformations, there is no report of an intracranial hemangiopericytoma found in association with multiple arteriovenous malformations and dural arteriovenous fistulae. We present the case of an otherwise healthy 25-year-old woman who presented with a large hemangiopericytoma involving the superior sagittal sinus. The highly vascular nature of the lesion, the total occlusion of the sinus anterior to the tumor, and the presence of multiple arteriovenous malformations and dural arteriovenous fistulae complicated resection of this tumor. To our knowledge, no prior report has described a tumor of this magnitude in association with multiple AVMs and dAVFs.


All-trans retinoic acid biases immune response induced by DNA vaccine in a Th2 direction.
Vitamin A deficiency diminishes Th2-mediated Ab responses. Providing Vitamin A or its active metabolites reverses this defect. All-trans retinoic acid (ATRA), an acid derivation of Vitamin A, regulates the balance of immune response induced by TR421-hCGbeta DNA vaccine. Compared to DNA vaccine alone or treatment with vehicle, significantly higher level of antibody against the protein encoded by DNA vaccine was observed in mice 6 weeks after the first immunization. The IgG2a/IgG1 ratio was lower in mice treated with ATRA. We also found that treatment with ATRA also diminishes specific cellular immune response induced by gene immunization by measuring the marker of cellular immune response. We conclude that ATRA biases the immune response to Th2 direction induced by DNA vaccine and acts as a candidate adjuvant and immunomodulatory molecule.


[Hepatitis C and diabetes mellitus: effect of diabetes on the course of the liver disease].
The prevalence of diabetes mellitus is higher in chronic hepatitis C than in hepatitis B, even without cirrhosis. To study the host, specific viral factors associated with diabetes mellitus and the influence of diabetes mellitus on the intensity of steatosis and the severity of fibrosis. The following data were collected in a cohort of 1249 patients with chronic hepatitis C established between December 1991 and June 2004: age, gender, body mass index (BMI). None of the patients were under treatment for their liver disease. Serum transaminase level and hepatitis C serology with search for viral RNA, viral load and genotype were obtained. The Metavir score, iron overload using the Perls score (0-4) and steatosis class (0-3) were determined on liver biopsies. Mean patient age was 52.5+/-10 years (56% male). Mean BMI was 24.6+/-24 kg/m2. Forty-three patients (17.2%) presented diabetes mellitus. The mean duration of their diabetes was 8.9 years. Genotype 1 predominated (60.4%) and mean viral load was 7.7x10(6) eq.v/ml. Steatosis was present in 69.7% of the diabetic patients versus 17% of the non-diabetic patients. Grade 2 fibrosis (F2) was observed in 32.5% of diabetic patients versus 29% in non-diabetic patients and F3, F4 in 73% of the diabetic patients versus 57% of the non-diabetic patients. Comparison between diabetic and non-diabetic patients demonstrated an absence of statistically significant difference (at 5%) between the groups for gender, viral load and genotype. Diabetic persons were older (58.7 years against 51 years) and liver biopsy revealed steatosis and fibrosis (F3, F4) more often in diabetic patients (69.7% versus 49.5%). These findings suggest that steatosis could favor progression of fibrosis in diabetics with chronic hepatitis C.


Low doses of fumonisin B1 exacerbate ochratoxin A-induced renal injury in mice and the protective roles of heat shock protein 70.
Fumonisin B1 (FB1) and ochratoxin A (OTA) possess nephrotoxicity to animals and widely co-exist in food and feedstuffs. FB1 rarely, while OTA often, causes toxicosis in animals. Heat shock protein 70 (Hsp70) resists lung injury induced by pneumolysin, but whether Hsp70 could remission mycotoxins-induced renal injury is still unknown. The present study aims to explore the impacts of nontoxic doses of FB1 on OTA-induced nephrotoxicity and the protective roles of Hsp70. In the mycotoxins-challenge experiment, ICR mice were co-exposed to nontoxic doses of FB1 (0, 0.2, 0.5, 1.0 mg/kg bw, IP) and toxic dose of OTA (0.4 mg/kg bw, IP) for 16 d. The results showed that the levels of BUN, Cr, MDA in serum, the Cyto C in renal tubes or glomerulus, pro-apoptosis genes and p-JNK protein expression in kidney were significantly increased. Histopathological results revealed the glomerular swelling. The above all indexes were dose-dependent. In the protection experiment, the mice were pretreated with the eukaryotic plasmid of pEGFP-C3-Hsp70, these increasing parameters in the mycotoxins-challenge experiment were reversed. In vitro, after pK-15 cells were treated with 8 μM FB1 and 5 μM OTA for 48 h, the mitochondrial membrane potential was significantly reduced, mitochondrial ROS was remarkably increased, more Cyto C was leaked from mitochondria into cytoplasm, and pro-apoptosis genes were significantly up-regulated. After the Hsp70 level was up-regulated by pEGFP-C3-Hsp70 or ML346 in pK-15 cells, these above indexes were reversed. However, activation of JNK by anisomycin significantly suppressed the protective effects of Hsp70. Our results demonstrate that the nontoxic doses of FB1 exacerbate the toxic dose of OTA-induced renal injury, while Hsp70 alleviates renal injury by inhibiting the JNK/MAPK signaling pathway. Hsp70 up-regulation may be an efficient strategy for protecting against tissue damage and bio-function impairment induced by co-exposure to FB1 and OTA.


Weight-based stigmatization, psychological distress, & binge eating behavior among obese treatment-seeking adults.
To evaluate the associations between weight-based stigmatization, psychological distress, and binge eating behavior in a treatment-seeking obese sample. Ninety-three obese adults completed three questionnaires: 1) Stigmatizing Situations Inventory, 2) Brief Symptoms Inventory, and 3) Binge Eating Questionnaire. Correlational analyses were used to evaluate the association between stigmatizing experiences, psychological distress and binge eating behavior. Stigmatizing experiences predicted both binge eating behavior (R(2)=.20, p<.001) and overall psychological distress (R(2)=.18, p<.001). A substantial amount of the variance in binge eating predicted by weight-based stigmatization was due to the effect of psychological distress. Specifically, of the 20% of the variance in binge eating accounted for by stigmatizing experiences, between 7% and 34% (p<.01) was due to the effects of various indicators of psychological distress. These data suggest that weight-based stigmatization predicts binge eating behavior and that psychological distress associated with stigmatizing experiences may be an important mediating factor.


Incremental risk of prior coronary arterial stents for pulmonary resection.
Many patients requiring lung cancer resection have concomitant coronary artery disease. Preoperative coronary artery stenting has been associated with increased risk of cardiac events after noncardiac surgery. Our aim was to determine the incidence of major adverse cardiac events (MACE) in patients undergoing pulmonary resection for lung cancer after percutaneous coronary stenting. This study uses Surveillance, Epidemiology, and End Results-Medicare data (1998 to 2005). Patients undergoing lung cancer resection within 1 year after coronary stenting were compared with patients without preoperative coronary intervention. The incidence and predictors of MACE within 30 days after surgery were determined. Five hundred nineteen patients underwent lung cancer resection after coronary stenting (stent), and 21,892 patients underwent lung cancer resection without a preceding coronary intervention (no stent). The stent group had higher comorbidity scores (p<0.0001) and more males (66% versus 50%; p<0.0001). There were no differences in age (74 versus 74 years), tumor size (33.7 versus 33.6 mm), stage (53% versus 54% stage I), and resections of lobectomy or greater (83% versus 80%) between stent and no-stent groups (all p>0.05). Thirty-day MACE and mortality rates were 9.3% and 7.7% in the stent group and 4.9% and 4.6% in the no-stent group (both p<0.0001). Multivariable predictors of MACE were coronary stent, age, male sex, comorbidity score, tumor size, and stage. Patients undergoing lung cancer surgery within 1 year of coronary stenting are at high risk for perioperative MACE. The presence of a coronary stent should be an important component of risk assessment before resection for lung cancer.


Arthroscopic debridement after intraarticular low-velocity gunshot wounds.
An unexpected degree of joint contamination was detected during arthroscopic debridement of three intraarticular, low-velocity gunshot wounds to the knee. When bullet wounds traverse a joint, it is recommended that clothing be inspected for fabric defects and that arthroscopy be considered for the surgical debridement.


Effect of photoperiod prior to cold acclimation on freezing tolerance and carbohydrate metabolism in alfalfa (Medicago sativa L.).
Cold acclimation proceeds sequentially in response to decreases in photoperiod and temperature. This study aimed at assessing the impact of photoperiod prior to cold acclimation on freezing tolerance and related biochemical and molecular responses in two alfalfa cultivars. The fall dormant cultivar Evolution and semi-dormant cultivar 6010 were grown in growth chambers under different photoperiods (8, 10, 12, 14 or 16h) prior to cold acclimation. Freezing tolerance was evaluated as well as carbohydrate concentrations, levels of transcripts encoding enzymes of carbohydrate metabolism as well as a K-3dehydrin, before and after cold acclimation. The fall dormant cultivar Evolution had a better freezing tolerance than the semi-dormant cultivar 6010. The effect of photoperiod prior to cold acclimation on the level of freezing tolerance differed between the two cultivars: an 8h-photoperiod induced the highest level of freezing tolerance in Evolution and the lowest in 6010. In Evolution, the 8h-induced superior freezing tolerance was associated with higher concentration of raffinose-family oligosaccharides (RFO). The transcript levels of sucrose synthase (SuSy) decreased whereas those of sucrose phosphatase synthase (SPS) and galactinol synthase (GaS) increased in response to cold acclimation in both cultivars. Our results indicate that RFO metabolism could be involved in short photoperiod-induced freezing tolerance in dormant alfalfa cultivars.


Perception of facial and dental asymmetries and their impact on oral health-related quality of life in children and adolescents.
The aim of this study was to investigate the perception of facial and dental asymmetries in children and adolescents and how these asymmetries affect their psychosocial and emotional well-being. The study included 66 children and adolescents (7-15 years) with a deviation between the maxillary and mandibular dental midlines of > 0.5 mm. The soft tissues of the face were scanned using stereophotogrammetry. Psychosocial and emotional impairments were assessed using the German version of the Child Perceptions Questionnaire (CPQ-G8-10 and 11-14). The mean midline deviation of the study group was 2.3 mm with no significant gender differences. Girls perceived facial asymmetry significantly more often than boys (p < 0.01). However, stereophotogrammetry showed no significant differences in facial morphology between subjects who perceived their face as asymmetrical and those who perceived it as symmetrical. Interestingly, we observed a significant correlation between the deviation of the dental midline and the lateral displacement of gonion (p < 0.05) and cheilion (p < 0.01). Psychosocial and emotional impairment was significantly higher in girls than in boys (p < 0.05). However, there was no significant correlation with the measured facial asymmetries. In contrast, the CPQ subscale score was 2.68 points higher in individuals with a dental midline shift ≥ 3 mm (p < 0.01), independent of age and gender. Although girls perceived facial asymmetries more strongly than boys do, this perception could not be objectified by extraoral measurements. A midline shift of 3 mm or more had a negative impact on the oral health-related quality of life of affected children and adolescents.


Menopausal symptoms, sexual function, depression, and quality of life in Korean patients with breast cancer receiving chemotherapy.
The purpose of this study was to study the relationships among menopausal symptoms, sexual function, depression, and quality of life in women with breast cancer undergoing chemotherapy. Two hundred women participated in this cross-sectional study. Data were collected with the Menopause Rating Scale (MRS), Female Sexual Function Index (FSFI), Beck Depression Inventory II (BDI-II), and the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B). Data were analyzed using descriptive statistics, t-tests, ANOVA, Scheffe's test, and Pearson product moment correlations using SPSS v. 20. Participants had alterations in menopausal symptoms and sexual function, and were depressed with a decreased quality of life. These factors are known to influence satisfaction with family support (p < 0.05) and sexual relationships (p < 0.05). Nurses should provide education to women with breast cancer on their sexual issues and encourage them to attend family support programs. They should also encourage family members to be proactive in addressing menopausal and depressive symptoms in these women with a goal to enhance their sexual functioning and quality of life.


Isolation frequency of Aeromonas species in relation to patient age.
Over a period of 18 months Aeromonas spp. were isolated from stool specimens of 116 patients (total isolation frequency 1.6%). Isolation rates in children up to ten years of age were significantly higher only for Aeromonas caviae as compared to other age groups. Additional data are needed to assess the clinical significance to these findings.


Renal and vascular outcomes in patients with isolated antiphospholipid syndrome nephropathy.
Antiphospholipid syndrome (APS) nephropathy (APSN) is a rare pattern with specific features resulting from microvascular lesions. The prognosis of APSN, outside of lupus nephritis, is unknown. The aim of this study was to describe the renal, vascular and overall outcomes of patients with APSN. Retrospective multicenter study of patients with antiphospholipid antibodies (aPL) associated with histological APSN lesions and no other nephropathy, identified through a national call for medical records. End-stage renal disease (ESRD)-free survival, thrombosis recurrence-free survival and overall survival were assessed. Thirty patients were included (19 women) with a median age of 40 years (34-52 years). Fifteen patients had APS, 26/28 had lupus anticoagulant, and 15/26 had triple positivity for aPL. Median eGFR was 50 (31-60) mL/min/1.73 m2. Glomerular thrombotic microangiopathy was found in 12/24 cases, fibrous intimal hyperplasia in 12/22 cases and focal cortical atrophy in 17/29 cases. Nineteen patients had moderate to severe interstitial fibrosis (>25%). Six patients developed ESRD at a median follow-up of 6.2 (1.8-9.1) years. The ESRD-free survival rates at 5 and 10 years were 80.0% (95% CI 57.6%-91.4%) and 72.7% (95% CI, 46.9%-87.4%) respectively. None of the histological factors considered was significantly associated with a decrease in eGFR at 12 months. Thrombosis recurrence-free survival was 77.8% (95% CI 48.2%-91.6%) at 10 years. Overall survival was 94% at 10 years (95% CI 65.0%-99.2%). The renal prognosis of isolated APSN is poor. The severe fibrotic lesions observed are suggestive of late diagnosis.


Long term follow-up study of laryngeal precancer.
The goal of this study was to determine subsequent malignancy on a discrete group of precancerous laryngeal lesions, and to assess the mortality. In a series of 227 patients, average age 51.8 years (ranging from 13 to 80 years). The changes were followed-up for 12.3 years (minimum of 5 years and maximum of 40 years). 58% are living without any sign of premalignant laryngeal mucosal disease, 13% with controlled precancer, and 3% in remission after surgery for carcinoma. 11% died (9% due to cause unrelated to the cancer) and 15% were lost for follow-up. 17% of the group with mucosal hyper- or metaplasia progressed to mild dysplasia, but none progressed to carcinoma. Reinke's oedema recurred in 4%, no malignancy was observed. Carcinoma developed in 16% of laryngeal papilloma (8% in situ and 8% invasive). 15% of mild dysplasia progressed in severity, but none transformed to malignancy. Moderate dysplasia progressed to severe dysplasia in 12%, carcinoma in situ in 4%. Of cases with severe dysplasia 13% developed in situ carcinoma while 43% progressed to invasive cancer. In the whole series progression to severe grade was seen in 7.1%, and malignant transformation in 4.4%. Three patients (1.3%) died due to subsequent carcinoma. Our results agree with some authors; but the majority of them reports higher incidence of malignant transformation. Invasive carcinoma was diagnosed in the follow-up in seven patients. Those represent only 3% of all laryngeal carcinomas diagnosed in our department in the same period of time. Based on the data we have evaluated the intensity of follow-up in patients with hyperplasia, metaplasia, keratosis and mild dysplasia.


Determination of hepatitis delta virus ribozyme N(-1) nucleobase and functional group specificity using internal competition kinetics.
Biological catalysis involves interactions distant from the site of chemistry that can position the substrate for reaction. Catalysis of RNA 2'-O-transphosphorylation by the hepatitis delta virus (HDV) ribozyme is sensitive to the identity of the N(-1) nucleotide flanking the reactive phosphoryl group. However, the interactions that affect the conformation of this position, and in turn the 2'O nucleophile, are unclear. Here, we describe the application of multiple substrate internal competition kinetic analyses to understand how the N(-1) nucleobase contributes to HDV catalysis and test the utility of this approach for RNA structure-function studies. Internal competition reactions containing all four substrate sequence variants at the N(-1) position in reactions using ribozyme active site mutations at A77 and A78 were used to test a proposed base-pairing interaction. Mutants A78U, A78G, and A79G retain significant catalytic activity but do not alter the specificity for the N(-1) nucleobase. Effects of nucleobase analog substitutions at N(-1) indicate that U is preferred due to the ability to donate an H-bond in the Watson-Crick face and avoid minor groove steric clash. The results provide information essential for evaluating models of the HDV active site and illustrate multiple substrate kinetic analyses as a practical approach for characterizing structure-function relationships in RNA reactions.


Felicitometric hermeneutics: interpreting quality of life measurements.
The use of quality of life (QOL) outcomes in clinical trials is increasing as a number of practical, ethical, methodological, and regulatory reasons for their use have become apparent. It is important, then, that QOL measurements and differences between QOL scores be readily interpretable. We study interpretation in two contexts: when determining QOL and when basing decisions on QOL differences. We consider both clinical situations involving individual patients and research contexts, e.g., randomized clinical trials, involving groups of patients. We note the ethical importance of such understanding: proper interpretation and communication facilitate health care decision making. Communication that facilitates interpretation is of moral significance since better communication can attenuate ethical problems and inform choices. Much of what is communication worthy about QOL assessments is determined by the particular QOL instrument used in the assessment and how it is administered. In practice, these choices will be driven by the purpose of the assessment, but, it is argued, to maximize understanding, we should combine the information garnered from traditional standardized QOL instruments, from individualized QOL assessments, and from a recently proposed dialogic paradigm, where QOL is determined by shared conversation regarding the interpretation of texts. And, while some studies can surely succeed using abbreviated methods of administration (e.g., postal surveys may suffice for certain purposes), we will focus on methods of administration involving interviewer-respondent interaction. We suggest that during the QOL elicitation process, interviewer and respondent should engage in a two-way conversation in order to achieve a shared understanding of the "answers" to QOL "questions" and, finally, to reach a shared interpretation of the individual's QOL.


On the preparation of bovine alpha-thrombin.
An improved method for the preparation of bovine alpha-thrombin is described. The procedure involves that activation of partially purified prothrombin with tissue thromboplastin followed by chromatography on Sulfopropyl-Sephadex C-50. The purified enzyme is homogeneous on polyacrylamide discontinuous gel electrophoresis and has a specific activity toward fibrinogen of 2.200-2,700 N.I.H. U/mg. Its stability on storage in liquid media is dependent on both ionic strength and temperature. Increasing ionic strength and decreasing temperature result in optimal stability. The denaturation of alpha-thrombin by guanidine hydrochloride was found to be a partially reversible process with the renatured species possessing properties similar to "aged" thrombin. In addition, the catalytic properties of alpha-thrombin covalently attached to agarose gel beads were also examined. The activity of the immobilized enzyme toward fibrinogen was affected to a much greater extent than was the hydrolysis of low molecular weight, synthetic substrates.


Ultrastructure of epiretinal membrane removed by pars plana vitreoretinal surgery.
Electron microscopic study of an epiretinal membrane obtained from a 69-year-old black woman during pars plana vitreoretinal surgery with vitreous hemorrhage complicating a retinal vein obstruction revealed extensive proliferations of fibrous astrocytes that had secreted fibrillar and basement-membrane collagens. Hemosiderin-containing macrophages were also found. Neovascular elements were present and appeared identical to normal retinal capillaries.


Colonic microflora: nutrition and health. Summary and conclusions of an International Life Sciences Institute (ILSI) [Europe] workshop held in Barcelona, Spain.
The colonic microflora is an organism that performs a variety of unique activities. It is more important to evaluate these activities than to analyze bacterial composition in terms of genera, species, or strains. Unless the bacteria translocate, it is the activities of the colonic microflora that affect colonic and systemic physiology and not the bacteria themselves.


Semi-bionic extraction of compound turmeric protects against dextran sulfate sodium-induced acute enteritis in rats.
Compound turmeric has been widely used as a remedy for infectious diseases in China. It is a classic multi-herb prescription in traditional Chinese medicine, commonly used in the treatment of enteritis, pneumonia, and abdominal pain for hundreds of years. However, throughout this history, the powder of multi-herbs was directly swallowed, which is currently difficult to administer to patients. The extract of Chinese herbal medicine is made by semi-bionic extraction technology, which is great progress in the modernization of powders of traditional Chinese medicine. The aim of this work is to investigate the protective effects of semi-bionic extraction of compound turmeric (SET) on acute enteritis (AE) induced by dextran sulfate sodium (DSS) in rats. SET was extracted in artificial gastric juice or artificial intestinal juice and mixed. After vacuum drying, the SET powder was dissolved in distilled water. Adult male Sprague-Dawley rats were randomly divided into six groups. Rats were given salazosulfapyridine (SASP, 175.0mg/kg) or SET (0.42 or 0.21g/kg) before intragastric administration of 5% DSS solutions (0.75g/kg). The treatments lasted 7 days. The food intake in 24h, disease activity index (DAI), and wet/dry (W/D) weight ratios and histological changes in colon tissue were measured. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, IL-8, and IL-10 in serum were determined at 1, 4, or 7 d after DSS challenge. Myeloperoxidase (MPO), malonaldehyde (MDA), diamine oxidase (DAO), and glutathione peroxidase (GSH-Px) activities in colon tissue were determined at 7 d. In addition, the nuclear factor-kappa (NF-κ B) and intercellular cell adhesion molecule-1 (ICAM-1) activations in colon tissue were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. In rats with AE, SET significantly reduced DAI at 7 d after DSS treatment, increased the body weight of rats and the food intake in 24h at 3 or 6 d after DSS challenge, and reduced the colon W/D ratio. SET also reduced the TNF-α, IL-6, IL-1β, and IL-8 in serum and increased IL-10 in serum at 4 and 7 d. In addition, SET decreased MPO, MDA, DAO, and GSH-Px activities in colon and attenuated histological changes in the colon at 7 d after DSS treatment. Further studies demonstrated that SET significantly inhibited NF-κB and ICAM-1 activations in colon tissue. The current study demonstrated that SET has potent protective effects on DSS-induced AE in rats through its anti-inflammatory and anti-oxidant activities.


Risk of Fracture and Osteoporosis in Patients With COPD and Inhaled Corticosteroids Treatment.
There are disputes whether inhaled corticosteroids (ICS) increase the incidence of fracture or osteoporosis among patients with COPD. The aim of this meta-analysis was to assess the effect of ICS treatment on the risk of fracture and osteoporosis in subjects with COPD. This study included parallel-group randomized controlled trials (RCTs) comparing ICS and control (non-ICS) therapy for subjects with COPD that reported adverse events including fractures or osteoporosis. Studies were found using MEDLINE/PubMed, Embase, and Cochrane Library databases between 1998-September 2022. Pooled risk ratios (RRs) and 95% CIs were calculated for primary outcomes. A total of 61,380 participants from 26 RCTs were included in the meta-analysis. Exposure to ICS did not increase the risk of fracture (RR 1.10 [95% CI 0.98-1.23], P = .10) or osteoporosis risk (RR 0.93 [95% CI 0.49-1.79], P = .84) in subjects with COPD. ICS use did not increase the incidence of fracture or osteoporosis in subjects with COPD.


Microwave induced synthesis of ZnO nanorods and their efficacy as a drug carrier with profound anticancer and antibacterial properties.
In the present study, we report the microwave-induced synthesis of fluorescent zinc oxide nanorods (ZnO) and their usage as a cargo material to carry hydrophobic drug, quercetin. TEM and SEM showed the rod-shape morphology of our synthesized ZnO. XRD showed several diffraction peaks correspond to a hexagonal wurtzite structure. The optical and chemical natures of these nanorods were also confirmed from the UV-vis (showed a distinct absorption bands from 361 to 395 nm) and FTIR spectrum (showed absorption band specific to Zn-O stretching). The synthesized ZnO also showed fluorescence emission at around 550 nm when excited under UV irradiation. Quercetin was loaded onto ZnO surface via employing a metal ion-ligand coordination bond, (ZnO/QR), which exhibit pH-sensitive release behavior. ZnO/QR displayed superior drug loading content (42%) and loading efficiency (72.4%). in vitro assays showed that ZnO/QR exhibited higher anticancer, as well as antibacterial activities compared with free quercetin and ZnO. All these results highlight the synthesis of ZnO nanorods under microwave irradiation, which can be used as a plausible therapeutic option for bioimaging and drug delivery purpose.