308 nm photolysis of nitric acid in the gas phase, on aluminum surfaces, and on ice films.
We have studied the photolysis of nitric acid (HNO(3)) in the gas phase at 253 and 295 K, on aluminum surfaces at 253 and 295 K, and on ice films at 253 K, by using 308 nm excimer laser photolysis combined with cavity ring-down spectroscopy. We monitored both the ground-state NO(2) and the electronically excited NO(2), NO(2)*, produced from the HNO(3) photolysis. NO(2)* + OH is a predominant photolysis pathway (if not the only photolysis pathway) from the gas-phase photolysis of HNO(3) at 308 nm. The NO(2)* quantum yields from the HNO(3) photolysis on aluminum surfaces are 0.80 +/- 0.15 at 295 K and 0.92 +/- 0.26 at 253 K, where errors quoted represent 2sigma measurement uncertainty. The corresponding NO(2)* quantum yield from the HNO(3) photolysis on ice films is 0.60 +/- 0.34 at 253 K. The 308 nm absorption cross sections of HNO(3) on Al surfaces and on ice films have been directly measured. Absorption cross sections of HNO(3) on Al surface at 308 nm are (4.19 +/- 0.17) x 10(-18) and (4.23 +/- 0.45) x 10(-18) cm(2)/molecule at 253 and at 295 K, whereas the corresponding absorption cross section of HNO(3) on ice films is (1.21 +/- 0.31) x 10(-18) cm(2)/molecule at 253 K (errors quoted represent 2sigma measurement uncertainty). Atmospheric implications of the results are discussed.


An Analysis of Cancer Registry Cost Data: Methodology and Results.
The Centers for Disease Control and Prevention initiated an economic analysis of the National Program of Cancer Registries (NPCR) in 2005 to estimate the true economic costs of operating a cancer registry, identify costs associated with registry activities, and evaluate the factors that may affect the efficiency of registry operations. We developed a Web-based NPCR cost assessment tool (NPCR-CAT) to collect activity-based cost data from all 48 NPCR registries. We collected data on registry funding, actual expenditures, and factors that may affect the efficiency of operating a central cancer registry. Key lessons learned during data collection and analysis include the importance of working closely with registry staff and balancing the need for standardized data elements with an understanding of individual registry characteristics. Our findings and lessons can be adapted to develop costing tools for other surveillance systems and cancer control programs, both domestically and internationally.


Performance enhancement in rally car drivers via heat acclimation and race simulation.
To investigate the combined use of an interactive racecar simulator and heat acclimation on psychomotor (driving) performance, eight rally drivers underwent 4 days of repeated heat (50 degrees C) exposure (1 h x day(-1)) during which they performed a simulated rally drive (3x12-min stages each separated by a 2-min break), after first cycling for 15 min at 125 W to induce some degree of fatigue and heat storage prior to beginning the rally. During the rally stages, a generic set of pace notes were read to the subject by a co-driver. In each simulation, sweat loss, heart rate, core (rectal) and skin temperatures were recorded and driving and psychomotor performance were assessed by recording stage times and time to complete a psychomotor test. Levels of physiological and perceived thermal strain were also recorded. Significant decreases in rally stage times (88 s; P<0.005), psychomotor test time (18 s; P<0.01), final core (0.25 degrees C; P<0.001) and skin (0.44 degrees C; P<0.005) temperatures, heart rate (16 beats x min(-1); P<0.05) and physiological (15 W x m(-2); P<0.005) and perceived thermal (3.7 units; P<0.01) strain were evident by the end of the final simulation, and a significant (P<0.05) increase in sweat sensitivity (+0.33 g x h(-1) x degrees C(-1)) was also recorded. These results suggest that both heat acclimation and race simulation can improve the psychomotor performance of rally drivers, although the relative contribution of each factor was not determined here. However, in a practical setting, these factors would not be used in isolation. After performing the acclimation and simulation protocol prior to an actual rally, drivers subjectively reported improvements in tolerating a high thermal load and in their ability to control the rally vehicle.


Decellularized scaffold-based poly(ethylene glycol) biomimetic vascular patches modified with polyelectrolyte multilayer of heparin and chitosan: preparation and vascular tissue engineering applications in a porcine model.
Mechanical property mismatch between vascular patches and native blood vessels can result in post-operation failure; therefore, vascular patches that mimic the biomechanical properties of native blood vessels must be developed. In this study, we constructed a biomimetic vascular patch by coating a poly(ethylene glycol) (PEG) film onto a decellularized scaffold (DCS) and modifying its surface with a heparin-chitosan polyelectrolyte multilayer (PEM). The PEM-modified PEG/DCS vascular patches exhibited comparable mechanical characteristics with native blood vessels. They effectively resisted platelet adhesion, reduced the hemolysis rate, increased the clotting time in vitro, and favoured the adhesion and growth of endothelial progenitor cells. In addition, the modified patches maintained long-term patency (5 months) of the treated arteries in vivo. Because of the synergistic effect of heparin and chitosan in PEM, the vascular patches may be able to manage medical complications. Thus, the PEM-modified PEG/DCS vascular patches may have promising applications in the repair of damaged or diseased blood vessels.


Performance of deterministic workplace exposure assessment models for various contaminant source, air inlet, and exhaust locations.
Contaminant concentration estimates from simple models were compared with concentration fields obtained by computational fluid dynamic (CFD) simulations for various room and source configurations under steady-state conditions. Airflow and contaminant distributions in a 10 x 3 x 7-m room with a single contaminant source on a 1-m high table were simulated using CFD for steady, isothermal conditions. For a high wall jet inlet, simulations were performed for nine room air exhaust locations and eight source locations. For a ceiling diffuser inlet the impact of two exhaust locations and eight source locations were investigated. Because CFD treats determinants of contaminant transport explicitly and agreed well with experimental results, it was used as the standard for comparison. Parameters of the one- and two-zone completely mixed models (CM-1 and CM-2) and the uniform turbulent diffusivity model (UD) were determined from CFD simulation results. Concentration estimates from these were compared with CFD results in the breathing zone (BZ) plane (1.5 m above the floor) for the entire BZ, the source "near field," and the source "far field." In the near field the mean percentage difference between the model concentration estimates and the CFD results for all room configurations were -21.9, 32.3, and 126% for the CM-1, CM-2, and UD models, respectively, with standard deviations of 26.8, 111, and 103%. In the far field the mean percentage difference between the model estimates and CFD results were -4.8, -2.3, and -36.3%. The CM-1 model had generally the best performance for applications such as occupational epidemiology for the conditions and configurations studied. However, CM-1 tended to underestimate the near field concentration; thus, CM-2 was judged to be better in the near field when underestimation is undesirable, such as when determining compliance with occupational exposure limits. The agreement of CM-2 estimates with CFD results in the near field was more variable than that of the CM-1. The UD model performed poorly on average in both near and far fields, and the difficulty in accurately estimating the turbulent diffusivity presents a significant impediment to UD model use for exposure estimation.


Implantation and testing of a novel episcleral pressure transducer: A new approach to telemetric intraocular pressure monitoring.
Measurement of intraocular pressure (IOP) is an essential tool in monitoring glaucoma. Single IOP assessments during clinical routine examinations represent punctual values and are not able to identify IOP fluctuations and spikes. Telemetric IOP measurements are able to monitor IOP during the day and night, and are location-independent. Six telemetric episcleral IOP sensors were investigated after minimally invasive subconjunctival implantation in 6 eyes of 6 New-Zealand-White rabbits. Three of the 4 edges of the implant were fixated intrasclerally with non-absorbable sutures. The sutures were stitched into the edges of the implants' silicone rubber encasements. Telemetric IOP measurements were validated 1 week, 4 weeks, 8 weeks, 12 weeks and 30 weeks after implantation. For each validation the anterior chamber was cannulated and connected to a height-adjustable water column. Different intracameral pressure levels (10-45 mmHg) were generated by height adjustment of the water column. Measurement reliability and concordance between telemetric and intracameral IOP was validated using Bland-Altman analysis. Overall comparison (10-45 mmHg) between telemetric and intracameral pressure revealed a standard deviation of ±1.0 mmHg. A comparison of pressure values in the range between 10 and 30 mmHg revealed a standard deviation of ±0.8 mmHg. Device deficiency was related to follow-up length: 4 weeks after implantation, 3 of the 6 sensors showed malfunction, with all sensors having failed 30 weeks after implantation. The most likely reason for the sensor malfunction is the loss of hermeticity as a result of penetration of the encasement during the episcleral fixation, resulting from the lack of preformed suture holes at the implants encasement. However, no clinical signs of injury or inflammation of the conjunctiva, sclera, implantation site or any other involved structures were observed, except for an expected mild short-term irritation postoperatively. The episcleral pressure transducer for telemetric IOP monitoring is able to assess IOP without the need for invasive intraocular surgery. Episcleral implantation is an easy and safe procedure and can be undone very easily, so even temporary implantation and IOP measurements could be possible in the future. Sensor malfunction over time is a problem that needs to be addressed. Improvements in sensor encapsulation and especially preformed suture holes could significantly decrease the failure rate and increase durability.


Alumina-on-alumina THA in patients with juvenile idiopathic arthritis: a 5-year followup study.
THA is a concern in juvenile idiopathic arthritis (JIA) owing to patients' youth, poor bone stock, and small physical size. We asked whether (1) uncemented alumina-on-alumina THAs have good clinical and radiographic results at midterm followup in young patients with inflammatory arthritis and end-stage hip disease secondary to JIA, and (2) the anatomic center of rotation of the hip could be reconstructed in patients with acetabular protrusion. We also assessed the rate of surgical complications. We retrospectively reviewed 31 alumina-on-alumina THAs in 21 patients with a mean age of 30.9 years (range, 14-48 years). Minimum followup until the time of revision of any component or the latest evaluation was 16 months. For nonrevised cases, the minimum followup was 60 months (range, 60-108 months). Acetabular protrusion was mild in 17 hips (Group 1) and moderate-severe in 14 (Group 2). Bone autograft was used to reconstruct the acetabulum in Group 2. Acetabular reconstruction was evaluated according to Ranawat et al. One cup was revised owing to aseptic loosening at 16 months; the remaining hips showed good clinical and radiographic results. The mean postoperative horizontal distance and the distance between the center of the head of the prosthesis and the true center of the femoral head improved in Group 2. There were no complications related to alumina. Although THA is a technically demanding procedure in patients with JIA, uncemented alumina-on-alumina THA provides pain relief and improves quality of life. In patients with acetabular protrusion, bone grafts enable anatomic cup positioning. Continued followup will be required to determine whether the alumina-on-alumina bearings in patients with JIA result in less osteolysis and loosening. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Iron(III)-chelating properties of the novel catechol O-methyltransferase inhibitor entacapone in aqueous solution.
The iron(III) complex formation of entacapone, a novel catechol O-methyltransferase (COMT) inhibitor, has been studied at 25 degrees C in aqueous 0.1 mol/L NaCl solution by using the electromotive force titration method. Entacapone functions as a bidentate ligand chelating through the catecholate oxygen atoms and forms stable iron(III) complexes with the formation constant of a tris complex: log beta-613 ([FeL3(3-)][H]6+/[Fe3+][H2L]3) = -6.9 +/- 0.1. Distribution curves show that entacapone is highly effective for iron(III) in moderately dilute solution (10(-3) mol/L) whereas in very dilute solution (10(-6) mol/L) the iron hydroxo complexes together with FeL3(3-) dominate under physiological pH 7.4. Comparison of iron(III) species distribution in a competitive two-ligand entacapone-catechol system reveals that the complexation of entacepone is favored at high and low dilution.


A fully synthetic four-component antitumor vaccine consisting of a mucin glycopeptide antigen combined with three different T-helper-cell epitopes.
In a new concept of fully synthetic vaccines, the role of T-helper cells is emphasized. Here, a synthetic antitumor vaccine consisting of a diglycosylated tumor-associated MUC1 glycopeptide as the B-cell epitope was covalently cross-linked with three different T-helper-cell epitopes via squaric acid ligation of two linear (glyco)peptides. In mice this four-component vaccine administered without external immune-stimulating promoters elicit titers of MUC1-specific antibodies that were about eight times higher than those induced by a vaccine containing only one T-helper-cell epitope. The promising results indicate that multiple activation of different T-helper cells is useful for applications in which increased immunogenicity is required. In personalized medicine, in particular, this flexible construction of a vaccine can serve as a role model, for example, when T-helper-cell epitopes are needed that match human leukocyte antigens (HLA) in different patients.


Effects of a 110 kilometers ultra-marathon race on plasma hormone levels.
To assess changes of sex hormones, cortisol, prolactin (PRL) and beta-endorphins in an exhaustive aerobic performance, blood samples were taken in 11 endurance trained runners (R) along an ultra-marathon race of 110 km (T1 before the start, T2 at km 33, T3 at km 75 and T4 immediately after completing the race). Results were compared to a control group (C) who followed the race. Cortisol (p < 0.001) and beta-endorphins (p = 0.009) showed a significant increase during the race without significant modification after T2. Testosterone decreased along the race (p = 0.02). Luteinising hormone (LH) was lower at the end of the race as compared to the start in the R. No modification of PRL was noticed in the runners. Most of the modifications except for testosterone were observed from the start to T2, even in exhaustive performance no further modification was noticed from that point onwards.


Serotonergic modulation of muscle acetylcholine receptors of different subunit composition.
Modulation of muscle acetylcholine (AcCho) receptors (AcChoRs) by serotonin [5-hydroxytryptamine (5HT)] and other serotonergic compounds was studied in Xenopus laevis oocytes. Various combinations of alpha, beta, gamma, and delta subunit RNAs were injected into oocytes, and membrane currents elicited by AcCho were recorded under voltage clamp. Judging by the amplitudes of AcCho currents generated, the levels of functional receptor expression were: alpha beta gamma delta > alpha beta delta > alpha beta gamma > alpha gamma delta. The alpha beta gamma delta and alpha beta delta AcChoR Subtypes were strongly blocked by 5HT, whereas the alpha beta gamma receptor was blocked only slightly. The order of blocking potency of AcChoRs by 5HT was: alpha beta delta > alpha beta gamma delta > alpha beta gamma. 5HT receptor antagonists, such as methysergide and spiperone, were even more potent blockers of AcChoRs than 5HT but did not show much subunit selectivity. Blockage of alpha beta gamma delta and alpha beta delta receptors by 5HT was voltage-dependent, and the voltage dependence was abolished when the delta subunit was omitted. These findings may need to be taken into consideration when trying to elucidate the mode of action of many clinically important serotonergic compounds.


Synthesis of dihydrodehydrodiconiferyl alcohol: the revised structure of lawsonicin.
Structural revision of lawsonicin, a natural product of Lawsonia alba, is reported based upon comparison of its spectral data with that of the naturally occurring dihydrobenzo[b]furan neolignan (rac)-trans-dihydrodehydrodiconiferyl alcohol, which is found to be identical. A concise synthesis of dihydrodehydrodiconiferyl alcohol, via Rh(2)[S-DOSP](4)-catalysed intramolecular C-H insertion, is described.


[Catheter tract embolization after percutaneous transhepatic biliary intervention].
Evaluation of the feasibility and efficacy of an embolization technique of the transhepatic tract after intervention, in order to prevent peritoneal bile leakage. Twenty patients (mean age 62 yr) with malignant (17 cases) or benign (three cases) biliary obstruction were treated by percutaneous transhepatic biliary intervention (stent implantation in 17 cases). Mean diameter of the transhepatic tract was 3.2 +/- 0.6 mm. Tract embolization was performed 3.0 +/- 4.0 days after intervention by injecting Histoacryl-Lipiodol via a coaxial catheter-sheath system. Tract embolization was feasible in all cases and resulted in a continuous cast of the catheter tract. There were no signs or symptoms of peritonitis in any of the patients. One patient with stent occlusion developed a biliocutaneous fistula via the former tract after 60 days. After embolization of fresh transhepatic tracts there were no signs of leakage during follow-up of the patients. One case with biliocutaneous fistula shows that prevention of leakage is not permanent if biliary reobstruction occurs.


Long-term influence of inhaled corticosteroids on bone metabolism and density. Are biological markers predictors of bone loss?
Long-term effects of high doses of inhaled corticosteroids (ICS) on bone density and metabolism are still uncertain. Fifty-one patients (37 male, 14 female) using beclomethasone or budesonide at a daily dose > 800 microgram/d (high-dose group [Group HD] mean: 983 microgram/d [prescribed dose x estimated compliance]) or no or < 500 microgram/d (control group [Group C] mean: 309 microgram/d) for more than 5 yr were enrolled in this study. Each had, 3 yr ago and at this last evaluation, a clinical evaluation and measurements of expiratory flows and of bone density and bone metabolism markers. Lumbar spine bone density (last visit) was similar in the two groups with respective values of 0.94 +/- 0.03 (HD) and 0.96 +/- 0.03 g/cm2 (C) (p > 0.05). T and Z scores were -1.21 +/- 0.19 and -0.70 +/- 0.18 (HD), -0.95 +/- 0.25 and -0.47 +/- 0.21 (C) respectively (p > 0.05). A correlation was found between the decrease in bone density and the mean daily dose of corticosteroid in Group HD although these changes were quite small, mean bone density being unchanged over the 3-yr period. Serum and urinary parameters were similar in the two groups. Furthermore, neither initial bone density nor any of the biological parameters could predict changes in bone density over a period of 3 yr. In conclusion, bone density was similar in both study groups and not significantly different over a 3-yr period. Neither initial bone density nor biological markers of bone metabolism helped to predict changes in bone mass.


The Concept of Health-Promoting Collaboration-A Starting Point to Reduce Presenteeism?
Background: Since presenteeism is related to numerous negative health and work-related effects, measures are required to reduce it. There are initial indications that how an organization deals with health has a decisive influence on employees' presenteeism behavior. Aims: The concept of health-promoting collaboration was developed on the basis of these indications. As an extension of healthy leadership it includes not only the leader but also co-workers. In modern forms of collaboration, leaders cannot be assigned sole responsibility for employees' health, since the leader is often hardly visible (digital leadership) or there is no longer a clear leader (shared leadership). The study examines the concept of health-promoting collaboration in relation to presenteeism. Relationships between health-promoting collaboration, well-being and work ability are also in focus, regarding presenteeism as a mediator. Methods: The data comprise the findings of a quantitative survey of 308 employees at a German university of applied sciences. Correlation and mediator analyses were conducted. Results: The results show a significant negative relationship between health-promoting collaboration and presenteeism. Significant positive relationships were found between health-promoting collaboration and both well-being and work ability. Presenteeism was identified as a mediator of these relationships. Conclusion: The relevance of health-promoting collaboration in reducing presenteeism was demonstrated and various starting points for practice were proposed. Future studies should investigate further this newly developed concept in relation to presenteeism.


Abnormalities of T lymphocyte subsets in systemic sclerosis demonstrated with anti-CD45RA and anti-CD29 monoclonal antibodies.
T cell subpopulations were assessed by two colour flow cytometry with phycoerythrin conjugated anti-CD45RA and anti-CD29 and fluorescein conjugated anti-CD4 and anti-CD8 monoclonal antibodies, on peripheral blood lymphocytes from 12 patients with systemic sclerosis and from nine control subjects. The percentage of CD4+CD29+ cells was significantly higher in patients with systemic sclerosis than in controls (mean (SEM) 68.8 (3.1) v 47.9 (4.1) respectively). CD4+CD45RA+ cells were not significantly different in patients and controls. CD8+CD29+ and CD8+CD45RA+ subpopulations were significantly higher in patients with systemic sclerosis than in controls (83.0 (3.2) v 58.7 (6.8) and 80.2 (3.0) v 66.9 (3.2) respectively). The increase in the percentage of CD29+ cells suggests an activation of memory cells in patients with systemic sclerosis, which may play an important part in the pathogenesis of the disease.


Cortical Inactivation Does Not Block Response Enhancement in the Superior Colliculus.
Repetitive visual stimulation is successfully used in a study on the visual evoked potential (VEP) plasticity in the visual system in mammals. Practicing visual tasks or repeated exposure to sensory stimuli can induce neuronal network changes in the cortical circuits and improve the perception of these stimuli. However, little is known about the effect of visual training at the subcortical level. In the present study, we extend the knowledge showing positive results of this training in the rat's Superior colliculus (SC). In electrophysiological experiments, we showed that a single training session lasting several hours induces a response enhancement both in the primary visual cortex (V1) and in the SC. Further, we tested if collicular responses will be enhanced without V1 input. For this reason, we inactivated the V1 by applying xylocaine solution onto the cortical surface during visual training. Our results revealed that SC's response enhancement was present even without V1 inputs and showed no difference in amplitude comparing to VEPs enhancement while the V1 was active. These data suggest that the visual system plasticity and facilitation can develop independently but simultaneously in different parts of the visual system.


Proteome-Wide Deconvolution of Drug Targets and Binding Sites by Lysine Reactivity Profiling.
Recently, numerous efforts have been devoted to identifying drug targets and binding sites in complex proteomes, which is of great importance in modern drug discovery. In this study, we developed a robust lysine reactivity profiling method to systematically study drug-binding targets and binding sites at the proteome level. This method is based on the principle that binding of a drug to a specific region of target proteins will change the reactivity of lysine residues that are located at this region, and these changes can be detected with an enrichable and lysine reactive probe. Coupled with data-independent acquisition (DIA), the known target proteins and corresponding binding sites were successfully revealed from K562 cell lysates for three model drugs: geldanamycin, staurosporine, and dasatinib. In addition, the drug-induced conformational changes of certain targets were also revealed by our method during the screening of staurosporine. The screening sensitivity of our method revealed from the screening of stuarosporine and dasatinib was comparable with that of thermal proteome profiling (TPP) or machine learning-based limited proteolysis (LiP-Quant). Overall, 21 and 4 kinase targets, including adenosine 5'-triphosphate (ATP)-binding targets, were identified for staurosporine and dasatinib in K562 cell lysates, respectively. We found that target proteins identified by TPP, LiP-Quant, and our method were complementary, emphasizing that the development of new methods that probe different properties of proteins is of great importance in drug target deconvolution. We also envision further applications of our method in proteome-wide probing multiple events that involve lysine reactivity changes.


IL-13 promotes the proliferation of rat pancreatic stellate cells through the suppression of NF-kappaB/TGF-beta1 pathway.
In chronic pancreatitis, pancreatic stellate cells (PSCs) play a central role in tissue fibrogenesis. Transforming growth factor beta(1) (TGF-beta(1)) and the Th2 lymphokines such as interleukin (IL)-13 are major profibrogenic cytokines in many organs. Activated PSCs produce various inflammatory cytokines including TGF-beta(1). In this study, we investigated whether IL-13 affects pancreatic fibrogenesis by modulating the functions of PSCs. IL-13 promoted PSCs proliferation without activation through the suppression of autocrine TGF-beta(1). IL-13 enhanced Stat6 phosphorylation in PSCs but Stat6 was not involved in the suppression of TGF-beta(1). IL-13 inhibited the transcriptional activity of NF-kappaB, and the expression of mutant I-kappaB reproduced the suppression of autocrine TGF-beta(1) and promoted PSCs proliferation. Taken together, we demonstrated that IL-13 promotes PSCs proliferation through the suppression of the transcriptional activity of NF-kappaB, resulting in the decrease of autocrine TGF-beta(1). This finding provides an unequivocal evidence of IL-13 participation in pancreatic fibrosis, illustrating a new strategy for chronic pancreatitis.


Characterization of human soluble high and low activity catechol-O-methyltransferase catalyzed catechol estrogen methylation.
The major detoxification pathway of the carcinogenic catechol estrogens is methylation by catechol- -methyltransferase (COMT). It has been hypothesized that the enzyme encoded by the low-activity allele (COMT(L) ) has a lower catalytic activity for catechol estrogen methylation than that encoded by the high activity allele (COMT(H) ). We expressed and purified human soluble (S)-COMT(H) and S-COMT(L) in and characterized the methylation of 2- and 4-hydroxyestradiol (2- and 4-OH-E2). There were no differences between the kinetic parameters for COMT(H) and COMT(L). The kinetic parameters for S-adenosylmethionine (SAM), the methyl donor in these reactions, also did not differ for COMT(H) and COMT(L). S-adenosylhomocysteine, the demethylated SAM metabolite, inhibited methylation of the catechol estrogens in a non-competitive manner similarly for COMT(H) and COMT(L). Each COMT substrate tested inhibited the methylation of other substrates in a mixed competitive and non-competitive fashion similarly for COMT(H) and COMT(L). Furthermore, in cytosolic fractions of COMT(HH)(MCF-10A and ZR-75-1) and COMT(LL)(MCF-7 and T47D) human breast epithelial cell lines, no differences were detected between the kinetic parameters of COMT with respect to 2- and 4-OH-E2 methylation; nor were COMT protein levels associated with the COMT genotype. These data suggest that the decreased COMT enzymatic activity that has been detected in human tissue in association with the COMT(L) allele is not reflected by differences in the affinity or capacity of COMT(H) and COMT(L) for catechol estrogen methylation. These results raise the question of what accounts for the difference in COMT activity associated with the COMT(HH) and COMT(LL) genotypes in human tissue.


[Autologous spleen transplantation].
Splenectomy is known to increase the risk of overwhelming bacterial infection. There is a decrease in immunoglobulin IgM, T-lymphocytes, impaired primary antibody response to antigen challenge, an altered opsonic function and a tuftsin deficiency. Splenic autotransplantation has been suggested as a method of preserving function and this concept is supported by experiments in animals (dogs). The study describes autotransplantation of the traumatized spleen in human beings for the preservation of splenic function. Eleven patients operated on for abdominal trauma in the Kenézy Hospital in Debrecen, required total splenectomy, than splenic autotransplantation. In these patients splenic slides were implanted in between two layers of omental pouch (Furka's "spleen chip"). In 10 patients the follow-up radionuclid imaging, the IgM level, and the tuftsin level unambiguously confirmed the functioning of the splenic tissue.


The Predictive Role of Artificial Intelligence-Based Chest CT Quantification in Patients with COVID-19 Pneumonia.
We sought to analyze the prognostic value of laboratory and clinical data, and an artificial intelligence (AI)-based algorithm for Coronavirus disease 2019 (COVID-19) severity scoring, on CT-scans of patients hospitalized with COVID-19. Moreover, we aimed to determine personalized probabilities of clinical deterioration. Data of symptomatic patients with COVID-19 who underwent chest-CT-examination at the time of hospital admission between April and November 2020 were analyzed. COVID-19 severity score was automatically quantified for each pulmonary lobe as the percentage of affected lung parenchyma with the AI-based algorithm. Clinical deterioration was defined as a composite of admission to the intensive care unit, need for invasive mechanical ventilation, use of vasopressors or in-hospital mortality. In total 326 consecutive patients were included in the analysis (mean age 66.7 ± 15.3 years, 52.1% male) of whom 85 (26.1%) experienced clinical deterioration. In the multivariable regression analysis prior myocardial infarction (OR = 2.81, 95% CI = 1.12-7.04, p = 0.027), immunodeficiency (OR = 2.08, 95% CI = 1.02-4.25, p = 0.043), C-reactive protein (OR = 1.73, 95% CI = 1.32-2.33, p < 0.001) and AI-based COVID-19 severity score (OR = 1.08; 95% CI = 1.02-1.15, p = 0.013) appeared to be independent predictors of clinical deterioration. Personalized probability values were determined. AI-based COVID-19 severity score assessed at hospital admission can provide additional information about the prognosis of COVID-19, possibly serving as a useful tool for individualized risk-stratification.


Information Functional Theory: Electronic Properties as Functionals of Information for Atoms and Molecules.
How to accurately predict electronic properties of a Columbic system with the electron density obtained from experiments such as X-ray crystallography is still an unresolved problem. The information-theoretic approach recently developed in the framework of density functional reactivity theory is one of the efforts to address the issue. In this work, using 27 atoms and 41 molecules as illustrative examples, we present a study to demonstrate that one is able to satisfactorily describe such electronic properties as the total energy and its components with information-theoretic quantities like Shannon entropy, Fisher information, Ghosh-Berkowitz-Parr entropy, and Onicescu information energy. Closely related to the earlier attempt of expanding density functionals using simple homogeneous functionals, this work not only confirms Nagy's proof that Shannon entropy alone should contain all the information needed to adequately describe an electronic system but also provides a feasible pathway to map the relationship between the experimentally available electron density and various electronic properties for Columbic systems such as atoms and molecules. Extensions to other electronic properties are straightforward.


Response to host density by the parasitoid Dolichogenidea tasmanica (Hymenoptera: Braconidae) and the influence of grapevine variety.
Natural enemies that respond to prey in a density-dependent manner may be able to quickly suppress pest populations before they reach economically damaging levels. Although it is primarily the combination of a natural enemy's functional response and a population numerical response that will influence the maximum number of pests attacked, other factors may influence a density-dependent response. We conducted large-scale field experiments, both artificially inoculating grapevines with larvae and using naturally occurring populations, to quantify and characterize the response of a parasitoid, Dolichogenidea tasmanica (Cameron) (Hymenoptera: Braconidae) to different densities of its host, the pest of grapevines, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae). We showed that the response of D. tasmanica to the density of E. postvittana was inversely density-dependent, and that the degree of parasitism was consistently and significantly higher in the grape variety Cabernet Sauvignon compared with Chardonnay. While the significant effect of variety on the degree of parasitism may provide an option for increasing the parasitism of E. postvittana by D. tasmanica, it also highlights how differences in host plant can influence trophic interactions.


A case of systemic anaplastic large cell lymphoma with 'Hodgkin-like' appearance and skin involvement mimicking lymphomatoid papulosis.
We report a unique case of the CD30+ anaplastic large cell lymphoma (ALCL). A 44-year-old Japanese male presented with lymphadenopathy followed by skin involvement. Initially, a swollen cervical lymph node was recognized in 1989 and relapsed in 1991, which was histologically diagnosed as Hodgkin disease of nodular sclerotic type. In 1996, he presented ulcerative cutaneous nodules and swollen lymph nodes in his left inguinal region, which was then diagnosed with CD30+ ALCL. Both the lymphadenopathy and the skin lesion had been completely remitted by combining chemotherapy followed by radiotherapy. Thereafter, he had relapsing and remitting episodes of multiple papules and nodules on his face, trunk and extremities for 10 years. Repeated histopathological examination revealed similar tumor cell proliferation in the papules/nodules of the skin. Essentially similar immunohistochemical features, including CD30 and granzyme B expression, but not anaplastic lymphoma kinase (ALK), strongly suggested that all these tumors were sequential expression of one disease continued for 19 years. This case was finally diagnosed as CD30+ ALCL with unique skin involvement mimicking lymphomatoid papulosis (LyP).


Deregulation of signaling pathways in acute myeloid leukemia.
In acute myeloid leukemia (AML), aberrant signal transduction enhances the survival and proliferation of hematopoietic progenitor cells. Activation of signal transduction in AML may occur through a variety of genetic alterations affecting different signaling molecules, such as the FLT3 and KIT receptor tyrosine kinases (RTKs) and members of the RAS family of guanine nucleotide-binding proteins. These mutant signaling proteins are attractive therapeutic targets; however, developing targeted therapies for each genotypic variant and determining the relationships between different genotypes and critical functional dependencies of the leukemic cells remain major challenges. As the large number of mutant signaling proteins that have been identified in AML are likely to reflect activation of a more limited number of downstream effector pathways, such as the RAF/MEK/ERK and PI3K/AKT cascades, targeting these unifying pathways may represent a more broadly applicable therapeutic strategy. Furthermore, integrative genomic studies combining DNA sequencing, DNA copy number analysis, transcriptional profiling, and functional genetic approaches hold great promise for identifying additional signaling abnormalities in AML that are relevant to leukemogenesis and can be exploited therapeutically. Eventually, it may become possible to use pathogenesis-oriented combinations of signal transduction inhibitors to improve the cure rate in AML patients.


1H NMR spectroscopy of Paracoccus denitrificans cytochrome c-550.
The 1H NMR spectra of ferri- and ferro-cytochrome c-550 from Paracoccus denitrificans (ATCC 13543) have been investigated at 300 MHz. The ferri-cytochrome c-550 shows hyperfine-shifted heme methyl resonances at 29.90, 29.10, 16.70, and 12.95 ppm and a ligand methionyl methyl resonance at -15.80 ppm (pH 8 and 23 degrees C). Four pH-linked structural transitions were detected in spectra taken as a function of pH. The transitions have been interpreted as loss of the histidine heme ligand (pK less than or equal to 3), ionization of a buried heme propionate (pK = 6.3 +/- 0.2), displacement of the methionine heme ligand by a lysyl amino group (pK congruent to 10.5), and loss of the lysyl ligand (pK greater than or equal to 11.3). The temperature behavior of hyperfine-shifted resonances was determined. Two heme methyl resonances (at 16.70 and 12.95 ppm) showed downfield hyperfine shifts with increasing temperature. The cyanoferricytochrome had methyl resonances at 23.3, 20.1, and 19.4 ppm. NMR spectroscopy did not detect the formation of a complex with azide. The second-order rate constant for electron transfer between ferric and ferrous forms was determined to be 1.6 X 10(4) M-1 s-1. Heme proton resonances were assigned in both oxidation states by cross-saturation and nuclear Overhauser enhancement experiments. Spin-coupling patterns in the aromatic region of the ferro-cytochrome spectrum were investigated.


Mathieu urethroplasty with preputial reconstruction and urethral stent urine drainage.
Foreskin reconstruction and urethral stent urine drainage were used successfully in 17 Mathieu urethroplasties. No significant complications occurred. The techniques and their advantages are outlined.


Bisphosphonate-related osteonecrosis of jaw (BRONJ) in Japanese population: a case series of 13 patients at our clinic.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) affects quality of life and is an important problem for dentists. A Japanese position paper on BRONJ was published in 2010. The purpose of this study was to review clinical data on the treatment of BRONJ obtained at the Clinic of Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba Hospital to further our understanding of this disease. A total of 13 patients (6 men and 7 women) were included. All the patients included in this study had received Bisphosphonate (BP) therapy and had BRONJ. Five of them (38.5%) had received oral BP therapy for osteoporosis, while the remaining 8 (61.5%) had received parenteral BP therapy for bone metastases from breast or prostate cancer. Osteoporosis patients were treated with risedronate or alendronate. Breast or prostate cancer patients were treated with zoledronate. Two patients with rheumatoid arthritis were treated with corticosteroid. Three patients had diabetes mellitus. Eleven patients were treated with antibiotics, while 5 underwent surgical treatment. Discontinuation of BP was recorded in 7 patients during dental treatment. Sequestration was observed in 6 patients during an 11-month follow-up. Eventually, healing and improvement of the oral mucosa were observed in 3 patients. The current standard treatment for BRONJ does not always provide good results. It is necessary to accumulate further clinical data to establish more effective treatment strategies for BRONJ.


Citrate regulates extracellular matrix mineralization during osteoblast differentiation in vitro.
The extremely high levels of citrate in bone highlight its important role, which must be involved in some essential functional or structural role that is required for the development and maintenance of normal bone. However, biomineralization researches have emphasized the interaction between the citrate and inorganic minerals during crystallization in cell-free systems. It is difficult to obtain a thorough and comprehensive understanding from cell-free experimental conditions and treatment methods. In this study, by proposing an osteoblast mineralization experimental model, we explored the regulation of citrate on bone apatite crystal structure. Our studies show that citrate stabilizes two precursors and then inhibits their transformation into hydroxyapatite. Concomitantly, the smaller size and lower crystallinity mineral deposition emerge during citrate-mediated osteogenic mineralization. These findings may provide a new perspective for the mechanism of osteogenic mineralization and a basis for further understanding of bone metabolism.


Interrogating Cellular Functions with Designer Janus Particles.
Janus particles have two distinct surfaces or compartments. This enables novel applications that are impossible with homogeneous particles, ranging from the engineering of active colloidal metastructures to creating multimodal therapeutic materials. Recent years have witnessed a rapid development of novel Janus structures and exploration of their applications, particularly in the biomedical arena. It, therefore, becomes crucial to understand how Janus particles with surface or structural anisotropy might interact with biological systems and how such interactions may be exploited to manipulate biological responses. This perspective highlights recent studies that have employed Janus particles as novel toolsets to manipulate, measure, and understand cellular functions. Janus particles have been shown to have biological interactions different from uniform particles. Their surface anisotropy has been used to control the cell entry of synthetic particles, to spatially organize stimuli for the activation of immune cells, and to enable direct visualization and measurement of rotational dynamics of particles in living systems. The work included in this perspective showcases the significance of understanding the biological interactions of Janus particles and the tremendous potential of harnessing such interactions to advance the development of Janus structure-based biomaterials.


The ChromaTest, a digital color contrast sensitivity analyzer, for diabetic maculopathy: a pilot study.
To assess the ability of the Chromatest in investigating diabetic maculopathy. Patients with Type 2 diabetes and no concurrent ocular pathology or previous laser photocoagulation were recruited. Visual acuities were assessed followed by colour contrast sensitivity testing of each eye using Chromatest. Dilated fundoscopy with slit lamp biomicroscopy with 78 D lens was then performed to confirm the stage of diabetic retinopathy according to the Early Treatment Diabetic Retinopathy Study. 150 eyes in 150 patients were recruited into this study. 35 eyes with no previous laser photocoagulation were shown to have clinically significant macular oedema (CSMO) and 115 eyes with untreated non-proliferative diabetic retinopathy (NPDR) on fundus biomicroscopy. Statistical significant difference was found between CSMO and NPDR eyes for protan colour contrast threshold (p = 0.01). Statistical significance was found between CSMO and NPDR eyes for tritan colour contrast threshold (p = 0.0002). Sensitivity and specificity for screening of CSMO using pass-fail criterion for age matched TCCT results achieved 71% (95% confidence interval: 53-85%) and 70% (95% confidence interval: 60-78%), respectively. However, threshold levels were derived using the same data set for both training and testing the effectiveness since this was the first study of NPDR using the Chromatest The ChromaTest is a simple, cheap, easy to use, and quick test for colour contrast sensitivity. This study did not achieve results to justify use of the Chromatest for screening, but it reinforced the changes seen in tritan colour vision in diabetic retinopathy.


Estrogenic activity of wastewater, bottled waters and tap water in Finland as assessed by a yeast bio-reporter assay.
Environmental pollutants appearing in wastewater, bottled mineral water, tap water, and bottled drinking water are potential, but yet poorly characterized, sources of human exposure to endocrine disrupting chemicals globally. Here, we investigated the current situation in the most densely populated region in Finland. Influent and effluent bi-monthly samples from a major wastewater treatment plant in Helsinki were obtained over a preceding 2-year period at two time-points (in 2011 and 2014). Equivalent samples from a household water purification plant (located in the same region) were also analyzed, together with various brands of bottled still and mineral water as well as tap water from residential buildings. Samples were obtained in one liter sterile containers, extracted by solid-phase extraction method, and their estrogenic potential determined by a yeast bioluminescent assay. The estrogenic activities of influent samples from the wastewater treatment plant in Helsinki were generally low (from less than limit of detection to 0.7 ng/L estrogen equivalent quantities (EEQ)), except in March and August 2011, when relatively high levels (14.0 and 7.8 ng/L EEQ, respectively) were obtained. Meanwhile, no estrogenic activity was recorded in any of the treated effluent samples from the wastewater treatment plant, influent and effluent samples from the drinking water plant, as well as tap water, bottled still, and mineral waters. These findings indicate that the purification method applied in Helsinki wastewater treatment plant, activated sludge with mechanical, chemical and biological purification steps, is effective in reducing estrogenic activity, and that tap or bottled waters are not a significant source of these compounds to the population in this region.


A SMRT approach for targeted amplicon sequencing of museum specimens (Lepidoptera)-patterns of nucleotide misincorporation.
Natural history collections are a valuable resource for molecular taxonomic studies and for examining patterns of evolutionary diversification, particularly in the case of rare or extinct species. However, the recovery of sequence information is often complicated by DNA degradation. This article describes use of the Sequel platform (Pacific Biosciences) to recover the 658 bp barcode region of the mitochondrial cytochrome c oxidase I (COI) gene from 380 butterflies with an average age of 50 years. Nested multiplex PCR was employed for library preparation to facilitate sequence recovery from extracts with low concentrations of highly degraded DNA. By employing circular consensus sequencing (CCS) of short amplicons (circa 150 bp), full-length barcodes could be assembled without a reference sequence, an important advance from earlier protocols which required reference sequences to guide contig assembly. The Sequel protocol recovered COI sequences (499 bp on average) from 318 of 380 specimens (84%), much higher than for Sanger sequencing (26%). Because each read derives from a single molecule, it was also possible to quantify the incidence of substitutions arising from DNA damage. In agreement with past work on sequence changes induced by DNA degradation, the transition C/G → T/A was the most prevalent category of change, but its rate of occurrence (4.58E-4) was so low that it did not impede the recovery of reliable sequences. Because the current protocol recovers COI sequence from most museum specimens, and because sequence fidelity is unaffected by nucleotide misincorporations, large-scale sequence characterization of museum specimens is feasible.


Organizational and activational effects of testosterone on masculinization of female physiological and behavioral stress responses.
The prevalence of affective disorders is two times greater in women than in men. The onset of anxiety and depression occurs at different ages that may correspond to key developmental periods when the brain is more vulnerable to hormonal and exogenous influences. Because stressful life events can precipitate disease onset, the development of greater stress sensitivity in females may contribute to their increased vulnerability. Gonadal hormone exposure in males during early development and again from puberty onward plays a prominent role in sexually dimorphic brain formation, possibly contributing to sex differences in stress responsivity. Therefore, organizational effects of testosterone propionate (TP) administered postnatally and activational effects of TP administered beginning at puberty on adult female physiological and behavioral stress responses were examined in mice. Although the activational effects of TP in females ameliorated the sex difference in the hypothalamic-pituitary-adrenal axis stress response, there was no effect of postnatal TP. Similarly, higher immobile time in intact females in the tail suspension test was blunted by activational TP in the absence of postnatal TP. However, in the marble-burying test of anxiety-like behaviors, organizational and activational TP independently resulted in increased burying behaviors. These results show that TP administration has distinct effects on reducing physiological and behavioral stress responsivity in rodent models and suggest that sex differences in these responses may partially result from the absence of testosterone in females.


[Misuse of emergency ambulance services].
The aim of the study was to investigate the incidence of misuse of ambulance emergency services for minor injuries in a defined area and population. Case records concerning all patients (2708) treated in the period 19.02-13.06.96 at the A&E departments at Holstebro and Herning Central Hospitals were reviewed. The following factors were predictive of use of ambulance for transportation to the A&E department in minor injuries: Traffic accident, age 18-25 years and injuries to head and back. Approximately 50% of all patients transported by ambulance emergency were estimated to have been able to be treated by general practitioners instead. In conclusion, although a certain amount of misuse of ambulance emergency services among patients treated for minor injuries were identified, the incidence of misuse was not more than 1.5/day in a population of appr. 200.000.


Microbial complement inhibitors as vaccines.
Complement inhibiting surface proteins of pathogenic bacteria provide candidates for vaccines because of two reasons. First, an immune response against them would recognize the microbes and secondly, it would neutralize the key bacterial virulence mechanism. Prerequisites for a vaccine protein include the following: (i) it should show limited variability, (ii) it should be immunogenic and the immune response against it should cover a sufficiently broad range of microbial strains, (iii) it should not be hidden beneath a capsule, long LPS O-polysaccharide side chains or a protein coat and (iv) it should not raise unwanted immune responses against host structures. Bacterial complement inhibitors often act by binding the soluble inhibitors factor H or C4 bp, by blocking C3 or C5 activation or by enzymatically cleaving key complement components. Inhibitors have been found from all major types of pathogens and may offer promise as rational vaccine candidates for preventing diseases such as meningococcal meningitis, systemic pneumococcal or group B streptococcal disease and Lyme borreliosis.


Effect of 12 weeks of complex training on occupational activities, strength, and power in professional firefighters.
Objective: This study examined the effects of 12-week complex training (CT) programs on professional firefighters' occupational activities, strength, and power. Methods: Thirty men professional firefighters were randomly assigned to the CT group (n = 15) and control group (n = 15). The CT group performed complex training and the control group completed resistance training (RT) twice a week over 12 weeks. The occupational activities, strength, and power were assessed at baseline and immediately after the intervention by measuring the performance of 100 m load-bearing run (100 m LR), 60 m shoulder ladder run (60 m SLR), 5 m × 20 m shuttle run (5 m × 20 m SR), 4th-floor climbing rope (4th-floor CR), countermovement jump with arm swing (CMJas), seated medicine-ball throw (SMT), one-repetition maximum bench press (1RM BP), and one-repetition maximum back squat (1RM BS). Results: The results showed that compared to RT, CT induced significantly greater improvements in 60 m SLR (p = 0.007), 4th-floor CR (p = 0.020), CMJas (p = 0.001), and SMT (p < 0.001). Conclusion: These findings suggest that CT is a novel intervention with great promise of improving professional firefighters' occupational activities, strength, and power.


Chromosome 17 abnormalities in pediatric neuroblastic tumor with abundant neuropil and true rosettes.
Although as a group, embryonal central nervous system tumors share a common background of primitive round cells, numerous distinctive histologic features allow for further subclassification. One tumor with a unique microscopic appearance is the recently described pediatric neuroblastic tumor with abundant neuropil and true rosettes (PNTANTR). We report 2 additional cases of this unusual tumor; both arose in 4-year-old children, one a midpontine tumor and the other a large cerebral lesion. The tumors contained hypercellular sheets of undifferentiated cells, broad zones of neuropil, and scattered perivascular, Homer Wright, and multilayered ependymoblastic-like rosettes. Isochromosome 17q was detected in multiple samples from one tumor, while the other tumor showed polysomy 17. No deletions of INI1 or amplifications of MYC or MYCN were detected. This report adds 2 cases to our experience of PNTANTR and is the first to demonstrate isochromosome 17q, a molecular alteration typical of medulloblastomas.


Enhanced intravenous urography in renal trauma with low-dose dopamine.
Intravenous pyelography is the standard first-line investigation for suspected renal trauma. A faint, and/or delayed visualization, or nonvisualization of the damaged renal unit is not uncommon. Low-dose dopamine (3 micrograms/kg/min) increases renal blood flow without deleterious side effects. An experimental rat model was developed to evaluate the effects of low-dose dopamine on intravenous pyelograms in animals with unilateral renal trauma. A consistent and significant improvement in the visualization of the injured kidney was noted in the dopamine-treated animals compared with controls that received equivalent volumes of normal saline.


Prevalence of Nasal Colonization with Staphylococcus aureus in Patients with Rheumatoid Arthritis.
Objetive: Patients with Rheumatoid Arthritis (RA) and nasal carriers of Staphylococcus aureus have an increased risk of developing infections caused by S. aureus. Our objective was to determine the prevalence of S. aureus nasal colonization in patients with RA and its relationship to RA treatments. Two hundred and seven patients with RA and 37 healthy controls were prospectively included in a cross-sectional study. A nasal secretion sample was collected by swab from both anterior nostrils and was referred to the hospital's microbiology department for culturing. The mean age of the patients (168 women, 78%) was 61 ± 12 years old. The mean disease duration was 13 ± 10 years. Seventy-six percent of the patients were positive for Rheumatoid Factor (RF), and 71% were positive for Anti-citrullinated Peptides Antibodies (ACPA). Seventy percent had joint erosions. The mean DAS28 was 3.1 ± 2.2. S. aureus nasal colonization was found in 36% of the RA patients and 35% of the controls. Three patients and no controls were resistant to oxacilin/ mupirocin. The patients who were positive for ACPA had a higher prevalence of S. aureus colonization (43% vs. 17%; p < 0.05). The colonization prevalence in the patients treated with glucocorticoids was 32% (n: 133); methotrexate and/or leflunomide, 37% (n: 167); anti-TNF agents, 46% (n: 54), p < 0.05 versus patients not treated with anti-TNF agents; rituximab, 22% (n: 18); tocilizumab, 39% (n: 18). The prevalence of S. aureus nasal colonization in patients with RA does not appear to be greater than that of the general population. Anti-TNF agents might confer a higher prevalence of colonization.


Indirect goal priming is more powerful than explicit instruction in children.
This study examined the relative efficacy of explicit instruction and indirect priming on young children's behavior in a task that required a series of choices between a small immediate reward and a larger delayed reward. One hundread and six 4-year-old children were randomly assigned to one of four conditions involving one of two goals (maximize rewards or obtain immediate rewards) and one of two types of instruction (indirect priming using stories or explicit verbal instructions). Children were more likely to make goal-congruent choices as a result of indirect priming, but there was no effect of explicit instruction, suggesting that indirect approaches to changing young children's behavior may be more effective than direct approaches under some circumstances. These results have implications for understanding the dynamic interplay between bottom-up and top-down influences on self-regulation early in development.


Surface chemistry and electrical properties of germanium nanowires.
Germanium nanowires (GeNWs) with p- and n-dopants were synthesized by chemical vapor deposition (CVD) and were used to construct complementary field-effect transistors (FETs). Electrical transport and X-ray photoelectron spectroscopy (XPS) data are correlated to glean the effects of Ge surface chemistry to the electrical characteristics of GeNWs. Large hysteresis due to water molecules strongly bound to GeO(2) on GeNWs is revealed. Different oxidation behavior and hysteresis characteristics and opposite band bending due to Fermi level pinning by interface states between Ge and surface oxides are observed for p- and n-type GeNWs. Vacuum annealing above 400 degrees C is used to remove surface oxides and eliminate hysteresis in GeNW FETs. High-kappa dielectric HfO(2) films grown on clean GeNW surfaces by atomic layer deposition (ALD) using an alkylamide precursor is effective in serving as the first layer of surface passivation. Lastly, the depletion length along the radial direction of nanowires is evaluated. The result suggests that surface effects could be dominant over the "bulk" properties of small diameter wires.


Four-way junctions in antisense RNA-mRNA complexes involved in plasmid replication control: a common theme?
In several groups of bacterial plasmids, antisense RNAs regulate copy number through inhibition of replication initiator protein synthesis. In plasmid R1, we have recently shown that the inhibitory complex between the antisense RNA (CopA) and its target mRNA (CopT) is characterized by the formation of two intermolecular helices, resulting in a four-way junction structure and a side-by-side helical alignment. Based on lead-induced cleavage and ribonuclease (RNase) V(1) probing combined with molecular modeling, a strikingly similar topology is supported for the complex formed between the antisense RNA (Inc) and mRNA (RepZ) of plasmid Col1b-P9. In particular, the position of the four-way junction and the location of divalent ion-binding site(s) indicate that the structural features of these two complexes are essentially the same in spite of sequence differences. Comparisons of several target and antisense RNAs in other plasmids further indicate that similar binding pathways are used to form the inhibitory antisense-target RNA complexes. Thus, in all these systems, the structural features of both antisense and target RNAs determine the topologically possible and kinetically favored pathway that is essential for efficient in vivo control.


In vitro and in vivo effects of adiponectin on bone.
Fat mass impacts on both bone turnover and bone density and is a critical risk factor for osteoporotic fractures. Adipocyte-derived hormones may contribute to this relationship, and adiponectin is a principal circulating adipokine. However, its effects on bone remain unclear. We have, therefore, investigated the direct effects of adiponectin on primary cultures of osteoblastic and osteoclastic cells in vitro and determined its integrated effects in vivo by characterizing the bone phenotype of adiponectin-deficient mice. Adiponectin was dose-dependently mitogenic to primary rat and human osteoblasts ( approximately 50% increase at 10 microg/ml) and markedly inhibited osteoclastogenesis at concentrations of 1 microg/ml or greater. It had no effect on osteoclastogenesis in RAW-264.7 cells or on bone resorption in isolated mature osteoclasts. In adiponectin knockout (AdKO) male C57BL/6J mice, trabecular bone volume and trabecular number (assessed by microcomputed tomography) were increased at 14 wk of age by 30% (P = 0.02) and 38% (P = 0.0009), respectively. Similar, nonsignificant trends were observed at 8 and 22 wk of age. Biomechanical testing showed lower bone fragility and reduced cortical hardness at 14 wk. We conclude that adiponectin stimulates osteoblast growth but inhibits osteoclastogenesis, probably via an effect on stromal cells. However, the AdKO mouse has increased bone mass, suggesting that adiponectin also has indirect effects on bone, possibly through modulating growth factor action or insulin sensitivity. Because adiponectin does influence bone mass in vivo, it is likely to be a contributor to the fat-bone relationship.


Finger dermatoglyphic variations in Rengma Nagas of Nagaland India.
The Rengma Nagas are one of the major Mongoloid tribal populations in the North-Eastern state of Nagaland in India. Population variation and sexual dimorphism in respect of finger dermatoglyphic characteristics in 207 adult individuals (104 males and 103 females) are reported in this present context. Frequency distribution of finger pattern types in different digits (both left and right sides combined) showed that whorls were the most prevalent patterns among both males (52.19%) and females (55.69%), followed by loops (47.70% in males and 42.81% in females). Significant sex differences in Dankmeijer Index (t = 1.47; p < 0.0001) and finger wise variations of total finger ridge count (TFRC) and absolute finger ridge count (AFRC) in both the sexes were recorded. However, in cases of the frequencies of finger dermatoglyphic pattern types, Pattern Intensity Index in fingers, TFRC and AFRC no significant sex differences were observed.


Tracking chromosome evolution in southern African gerbils using flow-sorted chromosome paints.
Desmodillus and Gerbilliscus (formerly Tatera) comprise a monophyletic group of gerbils (subfamily Gerbillinae) which last shared an ancestor approximately 8 million years ago; diploid chromosome number variation among the species ranges from 2n = 36 to 2n = 50. In an attempt to shed more light on chromosome evolution and speciation in these rodents, we compared the karyotypes of 7 species, representing 3 genera, based on homology data revealed by chromosome painting with probes derived from flow-sorted chromosomes of the hairy footed gerbil, Gerbillurus paeba (2n = 36). The fluorescent in situ hybridization data revealed remarkable genome conservation: these species share a high proportion of conserved chromosomes, and differences are due to 10 Robertsonian (Rb) rearrangements (3 autapomorphies, 3 synapomorphies and 4 hemiplasies/homoplasies). Our data suggest that chromosome evolution in Desmodillus occurred at a rate of ~1.25 rearrangements per million years (Myr), and that the rate among Gerbilliscus over a time period spanning 8 Myr is also ~1.25 rearrangements/Myr. The recently diverged Gerbillurus (G. tytonis and G. paeba) share an identical karyotype, while Gerbilliscus kempi, G. afra and G. leucogaster differ by 6 Rb rearrangements (a rate of ~1 rearrangement/Myr). Thus, our data suggests a very slow rate of chromosomal evolution in Southern African gerbils.


A two-part mixed-effects pattern-mixture model to handle zero-inflation and incompleteness in a longitudinal setting.
Two-part regression models are frequently used to analyze longitudinal count data with excess zeros, where the same set of subjects is repeatedly observed over time. In this context, several sources of heterogeneity may arise at individual level that affect the observed process. Further, longitudinal studies often suffer from missing values: individuals dropout of the study before its completion, and thus present incomplete data records. In this paper, we propose a finite mixture of hurdle models to face the heterogeneity problem, which is handled by introducing random effects with a discrete distribution; a pattern-mixture approach is specified to deal with non-ignorable missing values. This approach helps us to consider overdispersed counts, while allowing for association between the two parts of the model, and for non-ignorable dropouts. The effectiveness of the proposal is tested through a simulation study. Finally, an application to real data on skin cancer is provided.


Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?
Haemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta-mediated pregnancy complications. Although low-dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta-mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta-mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome-wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well-characterized placenta-mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placenta-mediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach.


Regio- and stereospecific oxidation of 9,10-dihydroanthracene and 9,10-dihydrophenanthrene by naphthalene dioxygenase: structure and absolute stereochemistry of metabolites.
The oxidation of 9,10-dihydroanthracene and 9,10-dihydrophenanthrene was examined with mutant and recombinant strains expressing naphthalene dioxygenase from Pseudomonas putida (NCIB 9816.4. Salicylate-induced cells of P. putida strain 9816/11 and isopropylthiogalactopyranoside-induced cells of Escherichia coli JM109(DE3)(pDTG141) oxidized 9,10-dihydroanthracene to (+)-cis-1R,2S)-1,2-dihydroxy-1,2,9,10-tetrahydroanthracene (> 95% relative yield; > 95% enantiomeric excess) as the major product. 9-Hydroxy-9,10-dihydroanthracene (< 5% relative yield) was a minor product formed by both organisms. The same cells oxidized 9,10-dihydrophenanthrene to (+)-cis-(3S,4R)-3,4-dihydroxy-3,4,9,10-tetrahydrophenanthrene (70% relative yield; > 95% enantiomeric excess) and (+)-(S)-9-hydroxy-9,10-dihydrophenanthrene (30% relative yield). The major reaction catalyzed by naphthalene dioxygenase with 9,10-dihydroanthracene and 9,10-dihydrophenanthrene was stereospecific dihydroxylation in which both of the previously undescribed cis-diene diols were of R configuration at the benzylic center adjacent to the bridgehead carbon atom. The results suggest that for benzocylic substrates, the location of benzylic carbons influences the type of reaction(s) catalyzed by naphthalene dioxygenase.


Ultrasound improves the outcomes of cardiopulmonary resuscitation in rats by stimulating the cholinergic anti‑inflammatory pathway.
The present study investigated the effects of the ultrasound (US), a noninvasive technique, on ischemia‑reperfusion injury (IRI) following cardiopulmonary resuscitation (CPR). The animals used in the present study were randomized into five groups (n=8 per group) as follows: i) The CPR group, where the rats underwent 6 min of untreated ventricular fibrillation (VF) followed by CPR and defibrillation; ii) the US group, in which the treatment was identical to the CPR group with the exception that rats were exposed to US treatment 24 h prior to CPR; iii) the MLA group, in which the treatment was identical to the US group with the exception that the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist MLA (4 mg/kg) was administered 30 min prior to US and VF respectively; iv) the GTS group, in which the treatment was identical to the CPR group with the exception that the α7nAChR agonist GTS‑21 (4 mg/kg) was injected 30 min prior to VF; and v) the SHAM group, in which the rats were exposed to surgical preparation without CPR and US application. At 1 day prior to CPR, the US treatment was administered to the left kidney by US pulses (contrast general mode with 9 MHz) with a bursting mechanical index of 0.72 for 2 min. Following treatment of the left kidney, the right kidney was exposed to identical US treatment for an additional 2 min. The results demonstrated that US preconditioning decreased the number of defibrillations required and shortened the duration of CPR. US also suppressed tumor necrosis factor‑α and interleukin‑6 levels following resuscitation (P<0.05), and a significantly longer overall survival time was observed in the US‑treated animals (P<0.01). In addition, US attenuated neuronal injury and promoted the expression of α7nAChR in hippocampal neurons (P<0.05). However, the protective effects of US were abolished by MLA and imitated by GTS‑21. The results of the present study demonstrated that prior exposure to US may improve animal outcomes following CPR, and the protective effects of US may be dependent on the cholinergic anti‑inflammatory pathway (CAP) via α7nAChR.


[Effect of electroacupuncture on GLP-1R/PI3K/Akt protein pathway in mice with Parkinson's disease].
To observe the effect of electroacupuncture(EA) on glucagon-like peptide-1 receptor (GLP-1R)/ phosphatidylinositol 3-kinase (PI3K)/ protein kinase B(Akt) protein pathway in the substantia nigra of mice with Parkinson's di-sease (PD),so as to explore its underlying mechanisms in treatment of PD. Forty-eight C57BL/6 male mice were randomly divided into normal, model, EA and inhibitor groups, with 12 mice in each group. PD mouse model was established by intragastrical administration of rotenone for 4 weeks. In the EA group, EA was applied at "Fengfu"(GV16), "Taichong"(LR3) and"Zusanli"(ST36) for 30 min, once daily, for 2 weeks. The mice of the inhibitor group received gavage of dipeptidyl peptidase-4 inhibitor ligliptin (10 mg·kg-1·d-1) once a day for 2 weeks. The behavioral scores of mice in each group were observed. The levels of tyrosine hydroxylase (TH) in serum and substantia nigra were detected by ELISA, and the protein relative expression levels of GLP-1R, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) in substantia nigra of midbrain of mice were detected by Western blot. Compared with the normal group, the behavioral scores were significantly increased (P<0.01), TH levels in serum and substantia nigra, protein expression levels of GLP-1R, p-PI3K and p-Akt of the substantia nigra in the model group were significantly decreased (all P<0.01). After intervention and in comparison with the model group, the behavioral scores were significantly decreased (P<0.01), TH levels and the protein expression levels of GLP-1R, p-PI3K and p-Akt in both EA and inhibitor groups were significantly increased (all P<0.01). There were no significant differences in the abovementioned indexes between EA group and inhibitor group (all P>0.05), except for TH levels which were considerably down-regulated in the EA group relative to the inhibitor group (P<0.01, P<0.05). EA at GV16, LR3 and ST36 may increase the level of TH in serum and substantia nigra by up-regulating the activity of GLP-1R/PI3K/Akt protein pathway, and improve the behavioral performance of PD induced by rotenone.


Measurement of perception thresholds for electrical noise stimuli.
In previous research, the application of sub-threshold electrical nerve stimulation (SENS) to peripheral nerves has been shown to improve tactile sensitivity. SENS has applications in the symptomatic treatment of a wide array of conditions that result in the loss of peripheral nerve function. These include diabetes, stroke, and age related peripheral neuropathy. The technology is dependent on careful control of the amplitude of the intervention stimulation relative to the user's perception threshold. However, little is known about the factors that influence the perception threshold and whether it can be treated as a constant. Here we present a study where we applied a two alternate forced choice paradigm to determine electrical perception threshold. We investigated participant, noise frequency characteristics, electrode location, electrode type, and electrode impedance characteristics as explanatory factors for the variability seen in the threshold outcome. We find that the electrical perception threshold is dependent on the frequency characteristics of the signal applied, but varies widely without correlation to the remaining variables. It was also highly variable when re-tested under identical conditions. Our results cast doubt on the ability to treat the electrical threshold as a single value that holds constant for a particular participant and electrode placement. This finding has significant implications in SENS applications.


Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study.
Subthreshold (retinal pigment epithelium) photocoagulation is a new photocoagulation method, which treats the retinal pigment epithelium (RPE) and avoids damage to the neural retina. The initial results in this prospective pilot study on various macular diseases are presented. 12 patients with diabetic maculopathy (group I), 10 with soft drusen (group II), and four with central serous retinopathy (CSR) (group III) were treated and followed up for 1 year. Treatment was achieved using a train of repetitive short laser pulses (1.7 micros) of a green Nd:YLF laser (parameters: 527 nm, 100 and 500 pulses, repetition rate: 500 Hz, spot size: 160 microm, energies: 70-100 microJ). Laser energy was based on the visibility of test lesions on fluorescein angiography (50-130 microJ). Patients were examined at various times by ophthalmoscopy, fluorescein and ICG angiography, and infrared imaging. After 6 months hard exudates disappeared in six out of nine patients in group I and leakage disappeared in six out of 12 diabetic patients. In group II drusen were less in seven out of 10 patients. In group III serous detachment disappeared in three out of four cases. Visual acuity was stable in all cases. None of the laser lesions was clinically visible immediately. After 1 day most lesions were visible as yellowish RPE depigmentation. After 3 months some of the lesions were visible as hyperpigmented areas but most were not. Fluorescein angiography showed leakage only in the first week. Infrared imaging showed that most lesions can be visualised in groups I and II after a period longer than 1 week as hyperreflective areas. This study showed that subthreshold (RPE) photocoagulation is effective in some cases of diabetic maculopathy, drusens, and in CSR. Visibility of laser burns is not always necessary in the treatment of macular diseases presented here. Infrared imaging is an effective and non-invasive way of visualising subthreshold (RPE) laser burns.


Feasibility and effectiveness of an online mindfulness meditation program for medical students.
The need to incorporate tools to promote medical student wellness in medical education is underscored by the concerning rates of psychological distress among them. The objective of this prospective cohort study was to obtain preliminary data on the feasibility and effectiveness of an online mindfulness intervention for medical student wellness. A convenience sample of 52 medical students consented to participate in this study. Feasibility was assessed by ease of recruitment, number of modules completed, satisfaction with the program, and adherence to a regular meditation practice. Participants completed the Maslach Burnout Inventory, the Jefferson Scale of Empathy-medical student version, the Five Face of Mindfulness Questionnaire-short form, and the Self Compassion Scale-short form pre and post intervention. The convenience sample was recruited within a two-month period. Forty-five participants completed at least one of seven modules. Descriptive statistics (mean±standard deviation) revealed that the mean number of modules completed was 4.85±2.7. Mean satisfaction with the modules was 7.07±1.1 out of 10. Adherence to a regular formal meditation practice was poor; the average amount of formal meditation practice per module was 34.14±27.44 minutes. Self-compassion and the "observe and describe" facets of mindfulness practice significantly statistically increased from baseline, but no such change was observed for levels of burnout and empathy. The present study indicates that an online mindfulness meditation program may be of interest to medical students. The results did not provide any evidence that the program was effective but we believe further research and development is warranted.


Dual Specific Phosphatase 14 Deletion Rescues Retinal Ganglion Cells and Optic Nerve Axons after Experimental Anterior Ischemic Optic Neuropathy.
Understanding molecular changes is essential for designing effective treatments for nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults older than 50 years. We investigated changes in the mitogen-activated protein kinase (MAPK) pathway after experimental AION and focused on dual specificity phosphatase 14 (Dusp14), an atypical MAPK phosphatase that is downstream of Krüppel-like transcription factor (KLF) 9-mediated inhibition of retinal ganglion cell (RGC) survival and axonal regeneration. We induced severe AION in a photochemical thrombosis model in adult C57BL/6 wild-type and Dusp14 knockout mice. For comparison, some studies were performed using an optic nerve crush model. We assessed changes in MAPK pathway molecules using Western blot and immunohistochemistry, measured retinal thickness using optical coherence tomography (OCT), and quantified RGCs and axons using histologic methods. Three days after severe AION, there was no change in the retinal protein levels of MAPK ERK1/2, phosphorylated-ERK1/2 (pERK1/2), downstream effector Elk-1 and phosphatase Dusp14 on Western blot. Western blot analysis of purified RGCs after a more severe model using optic nerve crush also showed no change in Dusp14 protein expression. Because of the known importance of the Dusp14 and MAPK pathway in RGCs, we examined changes after AION in Dusp14 knockout mice. Three days after AION, Dusp14 knockout mice had significantly increased pERK1/2+, Brn3A+ RGCs on immunohistochemistry. Three weeks after AION, Dusp14 knockout mice had significantly greater preservation of retinal thickness, increased number of Brn3A+ RGCs on whole mount preparation, and increased number of optic nerve axons compared with wild-type mice. Genetic deletion of Dusp14, a MAPK phosphatase important in KFL9-mediated inhibition of RGC survival, led to increased activation of MAPK ERK1/2 and greater RGC and axonal survival after experimental AION. Inhibiting Dusp14 or activating the MAPK pathway should be examined further as a potential therapeutic approach to treatment of AION. Abbreviations: AION: anterior ischemic optic neuropathy; Dusp14: dual specific phosphatase 14; ERK1/2: extracellular signal-regulated kinases 1/2; Elk-1: ETS Like-1 protein; GCC: ganglion cell complex; GCL: ganglion cell layer; inner nuclear layer; KO: knockout; MAPK: mitogen-activated phosphokinase; OCT: optical coherence tomography; RGC: retinal ganglion cell; RNFL: retinal nerve fiber layer.


Enhancement of neutrophil chemiluminescence after elective gastrointestinal surgery.
Neutrophil count and luminol-dependent chemiluminescence were measured pre-operatively and on the second, sixth and ninth days after operation in nine patients undergoing major, elective gastrointestinal surgery. The aim of the study was to test the hypothesis that elective surgery as a form of injury has no prolonged deleterious effect on neutrophil activity in non-septic patients. A significant increase in neutrophil count was demonstrated in all patients at Day 2 (P less than 0.01) and Day 9 (P less than 0.01). Neutrophil chemiluminescence increased on Day 2 and Day 6, the increase on Day 6 being significant (P less than 0.02). In the first 9 days after elective gastrointestinal surgery, a biphasic neutrophilia occurs and the metabolic response of neutrophils to an opsonized particle is not impaired. These data would support the hypothesis that major elective surgery has no deleterious effects on neutrophil activity, and indeed that neutrophil activity may be enhanced.


Purification and characterization of a heat-shock element binding protein from yeast.
The promoters of heat shock genes are activated when cells are stressed. Activation is dependent on a specific DNA sequence, the heat-shock element (HSE). We describe the purification to homogeneity of an HSE-binding protein from yeast (Saccharomyces cerevisiae), using sequential chromatography of whole cell extracts on heparin-agarose, calf thymus DNA-Sepharose and an affinity column consisting of a repetitive synthetic HSE sequence coupled to Sepharose. The protein runs as a closely spaced doublet of approximately 150 kd on SDS-polyacrylamide gels; mild proteolysis generates a stable 70-kd fragment which retains DNA binding activity. The relative affinities of the protein for a range of variant HSE sequences correlates with the ability of these sequences to support heat-inducible transcription in vivo, suggesting that this polypeptide is involved in the activation of heat-shock promoters. However, the protein was purified from unshocked yeast, and may therefore represent an unactivated form of heat-shock transcription factor. Study of the purified protein should help to define the mechanistic basis of the heat-shock response.


[Multidisciplinary approach of hip fractures based on Hungarian data].
Hip fractures are described by increased mortality, loss of quality of life, functional decline and burden of diseases. They show a growing number worldwide. The aim of the present study is to summarise the existing data on the incidence, mortality, complications and rehabilitation of hip fractures, which relevance is reported only by few studies. To reduce mortality and complications of hip fractures the authors emphasize the importance of primary treatment within 12 hours, appropriate selection of surgical methods corresponding to the fracture type after the assessment of femoral head viability, vitamin D supplementation, same conditions for primary treatment during everyday of the week, and an adequate acute treatment and rehabilitation for patient's general health status. In the future integrated processing of multidisciplinary results of hip fractures based on Hungarian data can support the development of efficient treatment and prevention strategies, which can be advantageous for the patient, families, health care system, and the society, too, by the reduction of costly complications of hip fracture healing and mortality. Orv. Hetil., 2016, 157(37), 1469-1475.


[Molecular mechanisms of ischemic-reperfusion syndrome and its personalized therapy].
Cardiovascular pathologies are the major causes of morbidity and mortality in the world. Cessation of the blood flow in large vessels, supplying tissues with oxygen and substrates, leads to ischemic conditions accompanied by unwanted shifts of oxidative metabolism and rise of the reactive oxygen species (ROS) generation. Small amounts of ROS are essential elements of the cell metabolism, however pathological elevation of ROS jeopardizes the survival of cells, organs and even organisms. Paradoxically, blood flow restoration during prolonged ischemia leads to oxidative stress that is often fatal for a live system. Oxygen paradox appears to be a limiting factor in clinical practice that intuitively seeks for immediate and complete restoration of a damaged blood flow. Mitochondrion is a major ROS source and a key element of pro-apoptotic signaling, however it is clear, that mitochondria are the main target for anti-ischemic treatment. In the present review we consider two ways of such anti-ischemic strategy, bringing ischemic tolerance to the organ through mitochondrial involvement, such as intrinsic, biological, or artificial, pharmacological adaptive systems (preconditioning). The latter is aimed to simulate elements and high efficiency of intrinsic protective system. The role of antioxidants in anti-ischemic therapy and their effects on preconditioning signaling are discussed in the review.


High expression of bone morphogenetic protein (BMP) 6 and BMP7 are associated with higher immune cell infiltration and better survival in estrogen receptor‑positive breast cancer.
There are conflicted experimental results on the role of bone morphogenetic proteins (BMPs) in cancer. Some results suggest that BMPs act as tumor suppressors while other findings indicate that BMPs are oncogenic factors. In the present study, we aimed to investigate the association of BMP expression and the survival of breast cancer patients utilizing The Cancer Genome Atlas (TCGA). High expression levels of BMP1 (P<0.001), BMP3 (P=0.002), BMP5 (P=0.002), BMP7 (P<0.001) and BMPR1A (P<0.001) were associated with better overall survival (OS). On the other hand, high expression levels of BMP6 (P<0.001), BMP8A (P=0.031), BMP8B (P<0.001) and BMPR1B (P=0.005) were associated with worse OS. Most of the BMPs demonstrated differential expression levels between normal and tumor tissues. High expression of BMP7 was found to be significantly associated with better prognosis in both estrogen receptor (ER)‑positive (ER+) (P<0.001) and ER‑negative (ER‑) tumors (P<0.001), whereas high expression of BMP6 was associated with better prognosis only in ER+ tumors (P=0.004); it was associated with worse prognosis in ER‑ tumors (P=0.006). In the ER+ tumors, high expression of BMP7 as well as BMP6 were associated with higher infiltration of anticancer immune cells and cytolytic activity. These results suggest that high expression levels of BMP7 as well as BMP6 possess higher anticancer immunity which results in better prognosis in ER+ breast cancer. In conclusion, BMP expression profiles may be useful for prognostication. Intervention in this pathway may serve to improve outcomes, manage metastatic disease and assist in clinical decision making on optimal therapy based on the risk of recurrence or metastasis.


Hemodialysis-related leukotriene B4 generation and neutropenia during calcium channel blockade.
Cuprophane membranes elict intense blood-surface interactions during clinical hemodialysis. The goal of the present studies was to determine whether calcium channel blockade may alter hemodialysis-related leukotriene B4 (LTB4) generation and neutropenia in 12 patients with end-stage renal failure. The patients were randomized to receive either placebo or nitrendipine for six weeks. Compared with untreated patients, the calcium channel blocker treatment group had significantly lower predialysis plasma LTB4 levels, Nitrendipine reduced both the magnitude of LTB4 generation and of neutropenia during the early phase of hemodialysis, but did not alter the close temporal relation of LTB4 accumulation and neutrophil activation. Therefore, the generation and release of LTB4 by neutrophils may be a calcium-dependent event. Furthermore, these results suggest that activation of neutrophil 5-lipoxygenase may contribute to the alterations in neutrophils of hemodialysis patients.


Abnormal expression of long non-coding RNA rhabdomyosarcoma 2-associated transcript (RMST) participates in the pathological mechanism of atherosclerosis by regulating miR-224-3p.
Study shows that long non-coding RNA (lncRNA) plays a regulatory role in cardiovascular diseases, and the mechanism of rhabdomyosarcoma 2-associated transcript (RMST) in atherosclerosis (AS) is still unclear. This study aimed to evaluate the expression of RMST and its possible role in the occurrence of AS. RMST and miR-224-3p level in serum and human umbilical vein endothelial cells (HUVECs) were determined by real-time quantitative PCR (RT-qPCR). In vitro atherosclerotic cell model was achieved by treating HUVECs with ox-LDL. Receiver operating characteristic (ROC) curve assessed the diagnostic value of RMST in AS, and Pearson correlation coefficient estimated the correlation of RMST with carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cfPWV). Cell counting kit-8 (CCK-8) assay and Enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the effect of RMST on cell viability and inflammatory response. The luciferase analysis was used to validate the relationship between RMST and miR-224-3p. The results showed that in serum and HUVECs, RMST levels were increased, while miR-224-3p level was decreased. ROC curve suggested that RMST had clinical diagnostic value for AS. Besides, CIMT and cfPWV were positively correlated with RMST levels, respectively. In HUVECs, RMST-knockdown notably improved the cell viability and inhibited the production of inflammatory factors. Moreover, miR-224-3p was the target of RMST. In conclusion, RMST has the potential to be a diagnostic marker for AS. RMST-knockdown contributes to the enhancement of cell viability and the inhibition of inflammatory response, which may provide new insights into the conquest of AS.


A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients.
Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incremental-cost-effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.


Reading(,) with and without commas.
All major writing systems mandate the use of commas to separate clauses and list items. However, casual writers often omit mandatory commas. Little empirical or theoretical research has been done on the effect that omitting mandatory commas has on eye movement control during reading. We present an eye-tracking experiment in Spanish, a language with a clear standard as to mandatory comma use. Sentences were presented with or without mandatory commas while readers' eye movements were recorded. There was a local increase in the go-past time for the pre-comma region when commas were presented, which was balanced out by shorter first-pass and second-pass times on the subsequent regions. In global sentence reading time, there was no evidence for an advantage of presenting commas. These findings suggest that, even when commas are mandatory, their effect is primarily to shift when processing takes place rather than to facilitate processing overall.


Cell wall yield properties of growing tissue : evaluation by in vivo stress relaxation.
Growing pea stem tissue, when isolated from an external supply of water, undegoes stress relaxation because of continued loosening of the cell wall. A theoretical analysis is presented to show that such stress relaxation should result in an exponential decrease in turgor pressure down to the yield threshold (Y), with a rate constant given by phiepsilon where phi is the metabolically maintained irreversible extensibility of the cell wall and epsilon is the volumetric elastic modulus of the cell. This theory represents a new method to determine phi in growing tissues.Stress relaxation was measured in pea (Pisum sativus L.) stem segments using the pressure microprobe technique. From the rate of stress relaxation, phi of segments pretreated with water was calculated to be 0.08 per megapascal per hour while that of auxin-pretreated tissue was 0.24 per megapascal per hour. These values agreed closely with estimates of phi made by a steady-state technique. The yield threshold (0.29 megapascal) was not affected by auxin. Technical difficulties with measuring phi by stress relaxation may arise due to an internal water reserve or due to changes in phi subsequent to excision. These difficulties are discussed and evaluated.A theoretical analysis is also presented to show that the tissue hydraulic conductance may be estimated from the T((1/2)) of tissue swelling. Experimentally, pea stems had a swelling T((1/2)) of 2.0 minutes, corresponding to a relative hydraulic conductance of about 2.0 per megapascal per hour. This value is at least 8 times larger than phi. From these data and from computer modeling, it appears that the radial gradient in water potential which sustains water uptake in growing pea segments is small (0.04 megapascal). This means that hydraulic conductance does not substantially restrict growth. The results also demonstrate that the stimulation of growth by auxin can be entirely accounted for by the change in phi.