Impact of Calcium Eccentricity on the Safety and Effectiveness of Coronary Intravascular Lithotripsy: Pooled Analysis From the Disrupt CAD Studies.
Coronary intravascular lithotripsy (IVL) safely facilitates successful stent implantation in severely calcified lesions. This analysis sought to determine the relative impact of lesion calcium eccentricity on the safety and effectiveness of IVL using high-resolution optical coherence tomography imaging. Individual patient-level data (n=262) were pooled from 4 distinct international prospective studies (Disrupt CAD I, II, III, and IV) and analyzed by an independent optical coherence tomography core laboratory. IVL performance in eccentric versus concentric calcification was analyzed by dividing calcified lesions into quartiles (≤180° [most eccentric], 181°-270°, 271°-359°, and 360° [concentric]) by maximum continuous calcium arc. In the 230 patients with clear imaging field on optical coherence tomography, there were no differences in preprocedure minimum lumen area, diameter stenosis, or maximum calcium thickness. The calcium length and volume index increased progressively with increasing mean and maximum continuous calcium arc (ie, concentricity). Conversely, the minimum calcium thickness decreased progressively with increasing concentricity. Post-procedure, the number of calcium fractures, fracture depth, and fracture width increased with increasing concentricity, with a 4-fold increase in the number of fractures in lesions with 360° of calcium arc compared with ≤180°. This increase in IVL-induced calcium fracture with increasing calcium burden and concentricity facilitated stent expansion and luminal gain such that there were no significant differences across quartiles. IVL induced calcium fractures proportional to the magnitude of coronary artery calcium, including in eccentric calcium, leading to consistent improvements in stent expansion and luminal gain in both eccentric and concentric calcified coronary lesions.


Effects of Adjacent Vehicles on Judgments of a Lead Car During Car Following.
Two experiments were conducted to determine whether detection of the onset of a lead car's deceleration and judgments of its time to contact (TTC) were affected by the presence of vehicles in lanes adjacent to the lead car. In a previous study, TTC judgments of an approaching object by a stationary observer were influenced by an adjacent task-irrelevant approaching object. The implication is that vehicles in lanes adjacent to a lead car could influence a driver's ability to detect the lead car's deceleration and to make judgments of its TTC. Displays simulated car-following scenes in which two vehicles in adjacent lanes were either present or absent. Participants were instructed to respond as soon as the lead car decelerated (Experiment 1) or when they thought their car would hit the decelerating lead car (Experiment 2). The presence of adjacent vehicles did not affect response time to detect deceleration of a lead car but did affect the signal detection theory measure of sensitivity d' and the number of missed deceleration events. Judgments of the lead car's TTC were shorter when adjacent vehicles were present and decelerated early than when adjacent vehicles were absent. The presence of vehicles in nearby lanes can affect a driver's ability to detect a lead car's deceleration and to make subsequent judgments of its TTC. Results suggest that nearby traffic can affect a driver's ability to accurately judge a lead car's motion in situations that pose risk for rear-end collisions.


Synthesis, complex formation and corneal permeation of cyclodextrin-modified, thiolated poly(aspartic acid) as self-gelling formulation of dexamethasone.
The present study aimed at developing a potential in situ gellable dexamethasone (DXM) eye drop. Poly(aspartic acid) (PASP) derivatives were synthesized with dual functionality to improve the solubility of DXM, and to achieve in situ gelation. First, amine-modified β-cyclodextrin (CD) was attached to polysuccinimide (PSI), second, thiol functionalities were added by the reaction of cysteamine and succinimide rings. Finally, the PSI derivatives were hydrolysed to the corresponding PASP derivatives to get water-soluble polymers. Phase-solubility studies confirmed the complexation ability of CD-containing PASP derivatives. In situ gelation and the effect of the CD immobilization on this behaviour were characterized by rheological measurements. The solubilizing effect of CD was confirmed by kinetic solubility measurements, whereas in vitro corneal permeability assay (corneal-PAMPA) measurements were performed to determine in vitro permeability and flux values. The effect of the PASP derivatives on permeation strongly depended on chemical composition and polymer concentration.


[Epidemiology of Pseudomonas aeruginosa hospital infection in the Ivory Coast].
210 P. aeruginosa hospital strains isolated at Abidjan from pathological samples or contaminated material were studied by means of serotyping, biotyping, phage-typing and for their resistance to eleven antibiotics. 87% were classified into 14 serogroups: O:1, O:2, O:3, O:4, O:5, O:6, O:8, O:9, O:10, O:11, O:12, O:13, O:15, O:16. No strains were O:7 or O:14. The presence of an ortho-nitrophenyl beta-d-galactopyranoside hydrolase was demonstrated in 42 strains belonging to the serogroup O:11. Sixty-five phage-types were defined but 37% of strains were untypable by phages. The incidence of resistance to each tested antibiotic was as follows: carbenicillin 49%, mezlocillin 44%, ticarcillin 34%, azlocillin 25%, cefamandole 94%, latamoxef 15%, cefotaxime 41%, cefsulodin 32%, tobramycin 35%, amikacin 7%, gentamicin 39%. Thirty-eight strains were multiresistant to carbenicillin, mezlocillin, ticarcillin, azlocillin, and four strains to eleven antibiotics. These results are compared with data of the scientific literature on the epidemiology of hospital Pseudomonas infection.


Iranian Nurses' Attitudes Toward Nurse-Physician Collaboration and its Relationship with Job Satisfaction.
Introduction: Although nurses and physicians are known to share the common goal of improving the quality of health care, there has traditionally been a relational gap between them. The aim of the present study was to investigate the attitude of Iranian nurses about physician-nurse collaboration and its relationship with their job satisfaction. Methods: In this cross-sectional study, a total of 232 nurses were recruited from three educational hospitals of Zanjan University of medical sciences. Three questionnaires were used in this study; (a) Demographic data questionnaire, (2) Jefferson Scale of Attitudes toward Physician-Nurse Collaboration (JSAPNC), and (3) Minnesota Satisfaction Questionnaire. Results: In this study, the mean age of the participants was 33.22(SD= 6.13) years, 83.8% of nurses were female, 90.8% had a baccalaureate degree in nursing, and 82.5 % had rotational work shifts. The mean score of physician-nurse collaboration was found to be 48.07 (SD= 8.95) (ranged from 15 to 60), and the mean score of job satisfaction scale was 57.78 (SD = 14.67) (ranged from 20 to 100). There was a significant positive correlation between the attitudes toward physician-nurse collaboration and job satisfaction among the nurses (r=0.59, P≤0.001). Conclusion: The results indicated that the collaboration between nurses and physicians increases the job satisfaction of nurses working in clinical settings. Therefore, nurses and physicians should develop a new culture of collaboration with each other with the mutual goal of high quality patient care. Moreover, health care administrators should implement the strategies that strengthen the development of physician-nurse collaboration.


Polarization-multiplexed multifocal arrays by a π-phase-step-modulated azimuthally polarized beam.
We demonstrate a polarization-multiplexed multifocal array capable of individually manipulating the focal polarization state in each focal spot. Breaking the rotational phase symmetry through adding a π-phase-step to an azimuthally polarized beam leads to a linear focal polarization state with high polarization purity. Through the superposition of such modulated azimuthal polarization fields at the back aperture of the objective, multifocal arrays with individually controllable and non-identical polarization states can be achieved. In addition, this approach exhibits a sub-diffraction-limited feature with an improved lateral resolution of 10% reduced full width at half-maximums in each linearly polarized focal spot. Consequently, applying this technique to parallel polarization-multiplexed optical recording is demonstrated.


Relationship between parent and child pedometer-determined physical activity: a sub-study of the CANPLAY surveillance study.
Understanding parental influences on their children's physical activity (PA) provides insight into developing effective family-based interventions. This study examines whether children's objectively monitored PA is associated with that of their parents. Participants (children and parents) were recruited to a sub-study of the Canadian Fitness and Lifestyle Research Institute's annual Canadian Physical Activity Levels among Youth (CANPLAY) surveillance study. In total, 539 of 1,187 eligible children (age range 5-19 years) and at least one of their parents participated. Participants logged pedometer steps for 7 days. Descriptive statistics were used to examine parental mean daily steps by their children's age, sex and steps/day. Associations between steps/day for parents and children (controlling for their age and sex) were estimated using general linear and logistic regression. Children's mean steps/day did not differ by parents' age or sex, nor by whether one or both parents participated in the study. There were quantifiable relationships between parents' and children's steps/day. For every 1,000 step increase in a father's steps/day, his son's increased by 329-407 steps/day and his daughter's increased by 273 steps/day (adjusted model only). Every 1,000 step increase in a mother's steps/day was associated with 263-439 extra steps/day for her son's steps/day and 195-219 steps/day for her daughter. A 3,000 step increment in a father's or mother's steps/day was associated with 1.9-2.5 fold increase in the odds that their child's activity level would be in the upper two tertiles of steps/day. These cross-sectional data indicate that children's PA is related to that of their parents in distinct and quantifiable ways. Interventions are warranted to evaluate the direction of this relationship, confirm the magnitude of influence, and illuminate mediating and moderating mechanisms by which both parents may have influence over their own children's PA.


Effects of fractionated radiation on the brain vasculature in a murine model: blood-brain barrier permeability, astrocyte proliferation, and ultrastructural changes.
Radiation therapy of CNS tumors damages the blood-brain barrier (BBB) and normal brain tissue. Our aims were to characterize the short- and long-term effects of fractionated radiotherapy (FRT) on cerebral microvasculature in mice and to investigate the mechanism of change in BBB permeability in mice. Intravital microscopy and a cranial window technique were used to measure BBB permeability to fluorescein isothiocyanate (FITC)-dextran and leukocyte endothelial interactions before and after cranial irradiation. Daily doses of 2 Gy were delivered 5 days/week (total, 40 Gy). We immunostained the molecules to detect the expression of glial fibrillary acidic protein and to demonstrate astrocyte activity in brain parenchyma. To relate the permeability changes to endothelial ultrastructural changes, we used electron microscopy. Blood-brain barrier permeability did not increase significantly until 90 days after FRT, at which point it increased continuously until 180 days post-FRT. The number of adherent leukocytes did not increase during the study. The number of astrocytes in the cerebral cortex increased significantly; vesicular activity in endothelial cells increased beginning 90 days after irradiation, and most tight junctions stayed intact, although some were shorter and less dense at 120 and 180 days. The cellular and microvasculature response of the brain to FRT is mediated through astrogliosis and ultrastructural changes, accompanied by an increase in BBB permeability. The response to FRT is delayed as compared with single-dose irradiation treatment, and does not involve leukocyte adhesion. However, FRT induces an increase in the BBB permeability, as in the case of single-dose irradiation.


Do the social sciences create phenomena?: the example of public opinion research.
This paper is an investigation into the philosophy and the history of the social sciences. Some philosophers of the social sciences have suggested that a key feature of the natural sciences is their capacity to create phenomena, and that the social sciences do not meet this criterion. We suggest, to the contrary, that the social sciences can and do create phenomena, in the sense of new ways of describing and acting that have been used to produce all sorts of effects. Like the natural sciences, the social sciences create their phenomena through the procedures that are established to discover them. But the creation of phenomena is a complex, technically difficult and contested process and its success rare. Historically, this argument is developed through a case-study of the development and evolution of public opinion research in the USA and Britain. We argue that by the 1950s public opinion produced a version of the world that had entered 'into the true'. Special attention is given to technical considerations in the development of public opinion research, especially the genealogy of a particular research technology, that of the representative sample. Whilst we are not concerned with demarcation criteria, we argue that there are some important differences between the social and the natural sciences; that the former have a less concentrated 'spatial mix' and a slower 'tempo of creativity'. None the less, in this particular case, the social sciences have played a key role in the creation of opinioned persons and an opinionated society.


Effects of biochar on reducing the abundance of oxytetracycline, antibiotic resistance genes, and human pathogenic bacteria in soil and lettuce.
Antibiotics and antibiotic resistance genes (ARGs) in soil can affect human health via the food chain. Biochar is a soil amendment but its impacts on ARGs and the microbial communities associated with soil and vegetables are unclear. Therefore, we established three lettuce pot culture experiments, i.e., O300: 300 mg/kg oxytetracycline (OTC), BO300: 300 mg/kg OTC + 2% biochar, and a control without OTC or biochar. We found that under BO300, the relative abundances of ARGs were reduced by 51.8%, 43.4%, and 44.1% in lettuce leaves, roots, and soil, respectively, compared with O300. intI1 was highly abundant in soil and lettuce, and it co-occurred with some ARGs (tetW, ermF, and sul1). Redundancy analysis and network analysis indicated that the bacterial community succession was the main mechanism that affected the variations in ARGs and intI1. The reduction of Firmicutes due to the biochar treatment of soil and lettuce was the main factor responsible for the removal of tetracycline resistance genes in leaves. Biochar application led to the disappearance of human pathogenic bacteria (HPB), which was significantly correlated with the abundances of ermF and ermX. In summary, biochar is an effective farmland amendment for reducing the abundances of antibiotics, ARGs, and HPB in order to ensure the safety of vegetables and protect human health.


Nano-Biochar Enhances Wheat Crop Productivity by Vindicating the Effects of Drought: In Relation to Physiological and Phenological Stages.
Climatic changes are major hindrances to crop productivity. Likewise, water scarcity is the major obstacle during different physiological and phenological stages, which ultimately reduces the wheat crop yield. So, there is a dire need to adopt modern approaches such as soil amendments, i.e., using nano-biochar (NBC) to boost soil health and wheat crop productivity. Therefore, a case study was performed in the wire house of the Agronomy Department, Faculty of Agriculture and Environmental Sciences, Islamia University of Bahawalpur. CRD (completely randomized design) with four treatments of NBC, i.e., NBC0 (control), NBC1 (0.5%), NBC2 (1.00%), NBC3 (1.5%), and four drought levels D0 = control, D1 = drought at tillering, D2 = drought at flowering, and D3 = drought at grain filling was used. The hypothesis for the case study was to investigate if the NBC increases crop productivity by boosting physiological and chemical attributes under different drought conditions at different phenological stages. Results showed that among NBC treatments, NBC2 (1.00%) showed 37.10% increase in peroxidase activity, 28.60% in superoxide dismutase, 63.33% in catalase, 22.03% in ascorbate peroxidase, and 6.66% in plant height as compared to other NBC treatments, whereas among drought treatments, D0 = control stood out in comparison to water deficit treatments at critical growth and development stages, statistically analyzed data revealed that D0 was able to generate plant height 6.17 times more, 12.76% in the number of grains per spike, 4.60% in osmotic potential, and 2.96% in stomatal conductance activities of wheat crop. D3 and NBC0 were identified as treatment levels with the statistically lowest growth and yield returns, respectively. It showed a decrease of 4.69% in leaf relative water contents, 12.33% in water potential, and 23.64% in fertile tillers. It was recommended that drought is avoided at any critical growth, particularly at the grain-filling stage. The use of organic substances (fertilizers) must be promoted as they possess soil and crop health-promoting properties and also reduce different management expenses (fertilizer cost). Using NBC helps boost crop growth in the presence of a limited water supply. However, extensive research is needed to find out the impact of these organic substances (humic acid, farmyard manure, and NBC) on different crops, particularly on wheat, under stress conditions.


Activity of novispirin G10 against Pseudomonas aeruginosa in vitro and in infected burns.
The emergence of multidrug-resistant microbes has serious implications for managing infection and sepsis and has stimulated efforts to develop alternative treatments, such as antimicrobial peptides. The objective of this study was to test a designer peptide, novispirin G10, against multidrug-resistant microorganisms. By two-stage radial diffusion assays, its activity against such organisms compared favorably with that of standard antibiotics and other antimicrobial peptides. It killed bacteria very rapidly, was nonhemolytic, and was relatively noncytotoxic. The peptide induced an immediate, massive efflux of potassium from Pseudomonas aeruginosa, suggesting that it altered the permeability of its inner membrane. The presence of human serum reduced but did not eliminate its activity. We tested the in vivo activity of novispirin G10 in rats with an infected, partial-thickness burn that covered 20% of their total body surface area. The burned area was seeded with 10(6) CFU of a Silvadene-resistant P. aeruginosa strain, and 24 h later a single treatment with 0, 1, 3, or 6 mg of synthetic novispirin G10 (n = 16 at each concentration) per kg was given intradermally. Significant bacterial killing (P < 0.0001) was evident within 4 h in each peptide group compared to controls receiving vehicle. Antimicrobial peptides such as novispirin G10 may provide a useful alternative or adjunct to standard antibiotic agents in treating burns or other wound infections.


Acute pancreatitis with pancreatic abscess secondary to sealed jejunal diverticular perforation.
Although most cases of acute pancreatitis are attributed to gallstones or alcohol, many remain idiopathic. The authors describe a case of acute pancreatitis in a 75-year-old gentleman who presented with acute epigastric pain, fevers and shortness of breath. Serum amylase was 2164. CT showed free mesenteric air, and a partly cystic/partly gas-containing mass in the uncinate lobe of the pancreas. Gastrograffin meal revealed duodenal and jejunal diverticular disease, but no contrast leak. Further CT analysis pinpointed fine tracts of air leading from a jejunal diverticulum up toward the pancreas, suggesting causation by a sealed jejunal diverticular perforation. He responded well to intravenous antibiotics and conservative management. Although small bowel diverticular disease is linked to chronic pancreatitis, evidence for association with acute pancreatitis is scarce. The authors believe this is the first reported case of jejunal diverticular disease causing acute pancreatitis, and it highlights micro-perforation as a potential disease mechanism.


Reconstruction of ischial pressure ulcers by skin expansion.
Ten patients, eight of whom were paraplegic, have had ischial pressure ulcers treated by skin expansion. Skin expanders 680 ml in size were inserted subcutaneously on the posterior aspect of the thigh. They were filled during a short period without complications, the filling being monitored with a cutaneous tonometer. At a second operation the ulcers were repaired easily with the expanded flaps. After a few weeks the patients were able to undergo a programme of rehabilitation that included sitting with the expanded flaps. No ulcers recurred during a median follow-up of 12 months (range 8-34).


The fibroblast growth factor receptor acid box is essential for interactions with N-cadherin and all of the major isoforms of neural cell adhesion molecule.
Interactions between the neural cell adhesion molecules NCAM and N-cadherin with the fibroblast growth factor receptor (FGFR) are important for a number of developmental events and have also been implicated in tumor progression. The factors regulating these interactions are not known. We have used co-immunoprecipitation and co-clustering paradigms to show that both adhesion molecules can interact with the 3Ig IIIC isoform of the FGFR1 in a number of cell types. Interestingly, whereas the interaction can be seen over most of the cell surface, it is not seen at points of cell-cell contact where the adhesion molecules accumulate at stable junctions. We also demonstrate for the first time that all of the major isoforms of NCAM can interact with the FGFR. Using deletion mutagenesis we have found that the adhesion molecule/FGFR interaction can withstand the removal of most of any one of the FGFR immunoglobulin-like domains (D1-D3). In contrast, the FGFR interaction with N-cadherin and NCAM (but not FGF) is absolutely dependant on the presence of the acid box motif that can be found in the linker region between D1 and D2. As this motif can be spliced out of all four FGFRs, it suggests that this is one mechanism that can regulate the interaction of the receptor with different ligand classes.


Electrocardiographic changes during antihypertensive treatment with diltiazem in relation to the achieved serum levels of the drug.
Diltiazem is a calcium channel blocker with antihypertensive and antiarrhythmic actions. In the present study 24 hypertensive patients were treated with diltiazem (180-360 mg daily) for 6 months. The effects on the electrocardiogram (ECG) were studied and were related to the serum levels of diltiazem. Treatment with diltiazem induced a non-significant reduction in heart rate with 3 beats min-1 and decreased blood pressure (-11/-9 mm Hg, p < 0.001). The treatment also induced a prolongation of the PQ-interval (+1.4 cs, p < 0.02), a prolongation only being weakly related to the plasma levels of diltiazem (r = 0.28, not significant) and its metabolite MA (r = 0.37, p = 0.07). Neither was the induced increase in the QT-interval (+0.9 cs, p < 0.05), significantly related to the plasma levels of diltiazem. In conclusion, the plasma levels of diltiazem were not clearly related to the induced changes at the ECG during antihypertensive treatment.


Colonization dynamics of ampicillin-resistant Escherichia coli in the infantile colonic microbiota.
To compare the colonization dynamics of ampicillin-resistant and ampicillin-susceptible Escherichia coli strains in the infantile intestinal microbiota. We followed 128 infants over the first year of life with regular quantitative faecal cultures and recordings of antibiotic treatment. E. coli strains were quantified, and their resistance pattern and carriage of beta-lactamase genes (TEM, SHV and OXA), phylogenetic group (A, B1, B2 or D), virulence gene profile (fimA, papC, sfaD/E, kfiC neuB, hlyA and iutA) and time of persistence in the microbiota were determined. Twelve percent (n = 32) of the E. coli strains were resistant to ampicillin, as they carried the bla(TEM) (84%) or bla(SHV) genes. Ampicillin-resistant strains belonged mostly to phylogenetic group D and carried pap genes (P = 0.023) significantly more often than ampicillin-susceptible strains due to a strong association between carriage of pap and bla(SHV). In 31 of 32 cases, colonization by ampicillin-resistant strains occurred in infants not previously treated with beta-lactam antibiotics. Ampicillin-resistant strains were equally capable as susceptible ones of persisting in the intestinal microbiota and did not have lower faecal population counts. Genes encoding beta-lactamases were in most cases retained during the entire colonization period. The results suggest that ampicillin-resistant E. coli strains are not hampered in their colonizing capacity, and beta-lactamase genes, therefore, may only slowly be eliminated from the commensal E. coli strain pool.


Postoperative assessment of extracranial-intracranial bypass by time-resolved 3D contrast-enhanced MR angiography using parallel imaging.
Our goals were to assess image quality of time-resolved contrast-enhanced MR angiography (CE MRA), by using 3D data acquisition along with a parallel imaging technique that can improve temporal resolution and to compare this technique with 3D-time-of-flight (TOF) MRA in the postoperative assessment of extracranial (EC)-intracranial (IC) bypass surgery. On a 1.5T imaging system, we performed CE MRA by using a 3D fast field-echo sequence in combination with a parallel imaging technique, to obtain images in the coronal plane centered at the postoperative site. Our patient group comprised 17 patients, including 13 after superficial temporal artery-middle cerebral artery (MCA) anastomosis, 3 after external carotid artery-MCA anastomosis, and one after extracranial vertebral artery-posterior cerebral artery anastomosis. Visualization of the anastomosis and the distal flow on the CE-MRA images was assessed comparatively with that on 3D-TOF MR angiograms obtained at the same time. In 6 patients, we also compared the efficiency of visualization on CE-MRA images with that on conventional angiograms. A temporal resolution of 0.8 s/frame could be achieved with the technique employed. The bypass was better demonstrated postoperatively on CE-MRA images than on 3D-TOF MR angiograms in 13 patients (76%), whereas the 2 methods were equivalent in 4 patients (24%). Good correspondence of results was observed in the 6 patients for whom CE MRA and conventional digital subtraction angiography (DSA) images were compared. CE MRA by using the parallel imaging technique can increase image acquisition speed with sufficient image quality. This technique is at least equivalent to 3D-TOF MRA to evaluate the postoperative status of EC-IC bypass.


A 13-week vapor inhalation study of n-hexane in rats with emphasis on neurotoxic effects.
Male and female Fischer 344 rats were exposed to 0-, 3000-, 6500-, or 10,000-ppm n-hexane vapors 6 hr per day, 5 days per week, for 13 weeks. The 13-week exposures had no adverse effect on the growth of female rats. However, the mean body weight gain of male rats in the 10,000-ppm group was significantly lower than for controls at 4 weeks of exposure and thereafter. In addition to the depression of body weight gain, the male exposed to 10,000 ppm had slightly but significantly lower brain weights at necropsy. No adverse testicular effects were noted. Axonopathy was observed in the tibial nerve in four of five male rats from the 10,000-ppm group and one of five male rats in the 6500-ppm group and in the medulla from one male rat in the 10,000-ppm group. These axonal changes were detectable only in teased nerve fiber preparations or in Epon embedded specimens. Histopathologic studies on Formalin fixed tissues did not reveal any lesions that were attributed to n-hexane exposure.


Management of the difficult airway.
Management of difficult airway is one of the most challenging tasks for anesthesiologists, and failure of securing it could have fatal consequences. We must be prepared to deal with problems in management of difficult airway at any time. Difficult intubation can either be anticipated or unanticipated. An anesthesiologist must be aware of the possibility of both situations to arise and preparations must be taken to deal with such cases and improve the safety of our patients. Practice guidelines are systematically developed recommendations that help anesthesiologists in the management of difficult airway.


Enamine/enolate-mediated organocatalytic azide-carbonyl [3+2] cycloaddition reactions for the synthesis of densely functionalized 1,2,3-triazoles.
Organocatalytic click! Recent advances in the metal-free enamine/enolate-mediated azide-carbonyl [3+2] cycloaddition reaction are discussed. These approaches require neither a metal catalyst nor alkyne substrates. Owing to the ready availability of carbonyl compounds, these methods thus offer excellent alternatives for the synthesis of 1,4-/1,5-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles.


Metabolomic Analysis of Vitamin E Supplement Use in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
The effects of vitamin E supplementation on cancer and other chronic diseases are not clear. We compared the serum metabolomic profile of differing vitamin E dosages in order to re-examine the previously observed changes in a novel C22 lactone sulfate compound, androgenic steroids, and other metabolites. A total of 3409 women and men previously selected for metabolomics studies in the PLCO Cancer Screening Trial were included in this investigation. Serum metabolites were profiled using ultrahigh-performance liquid and gas chromatography/tandem mass spectrometry. Seventy known metabolites including C22 lactone sulfate and androgens were significantly associated with vitamin E supplementation. In the sex-stratified analysis, 10 cofactors and vitamins (e.g., alpha-CEHC sulfate and alpha-CEHC glucuronide), two carbohydrates (glyceric and oxalic acids), and one lipid (glycocholenate sulfate) were significantly associated with vitamin E dose in both males and females (FDR-adjusted p-value < 0.01). However, the inverse association between C22 lactone sulfate and daily vitamin E supplementation was evident in females only, as were two androgenic steroids, 5-androstenediol and androsterone glucuronide. Our study provides evidence of distinct steroid hormone pathway responses based on vitamin E dosages. Further studies are needed to gain biological insights into vitamin E biochemical effects relevant to cancer and other chronic diseases.


Localized gastric cancer treated with chemoradation without surgery: UTMD Anderson Cancer Center experience.
In patients with localized gastric cancer (LGC) who are unfit for surgery, decline surgery, or have unresectable cancer, chemoradiotherapy may provide palliation; however, data in the literature are sparse. We identified 66 LGC patients who had definitive chemoradiation but no surgery. All patients had baseline and postchemoradiation staging including an endoscopic biopsy. Multiple statistical methods were used to analyze outcomes. Most patients were men and most had stage III or IV cancer. Five patients were surgery eligible but declined to have surgery. The median follow-up time was 33.9 months (95% CI 18.3-49.6). The median survival time (MST) for 66 patients was only 14.5 months (95% CI 10.8-19.7) and the median relapse-free survival (RFS) was 5.03 months (95% CI 4.67-6.40). The estimated overall survival (OS) and RFS rates at 3 years were 22.6% (95% CI 13.7-37.3) and 7.7% (95% CI 3.2-18.6), respectively. Twenty-three (35%) patients who achieved a clinical complete response (cCR; negative postchemoradiation biopsy and no progression by imaging) fared better than those who achieved less than cCR (<cCR) [cCR: MST 30.7 months (95% CI 20.4-NA); <cCR: MST 10.6 months (95% CI 8.43-14.9); p < 001]. In multivariate analysis, cCR was the only independent prognosticator for OS [hazard ratio (HR) = 0.32, p < 0.0012] and RFS (HR = 0.12, p < 0.0001). Our data demonstrate that in the absence of surgery, outcomes with definitive chemoradiation are only modest. A third of the patients achieved cCR and had a longer OS and RFS than those who achieved <cCR.


Transcriptome-Wide Analysis of Botrytis elliptica Responsive microRNAs and Their Targets in Lilium Regale Wilson by High-Throughput Sequencing and Degradome Analysis.
MicroRNAs, as master regulators of gene expression, have been widely identified and play crucial roles in plant-pathogen interactions. A fatal pathogen, Botrytis elliptica, causes the serious folia disease of lily, which reduces production because of the high susceptibility of most cultivated species. However, the miRNAs related to Botrytis infection of lily, and the miRNA-mediated gene regulatory networks providing resistance to B. elliptica in lily remain largely unexplored. To systematically dissect B. elliptica-responsive miRNAs and their target genes, three small RNA libraries were constructed from the leaves of Lilium regale, a promising Chinese wild Lilium species, which had been subjected to mock B. elliptica treatment or B. elliptica infection for 6 and 24 h. By high-throughput sequencing, 71 known miRNAs belonging to 47 conserved families and 24 novel miRNA were identified, of which 18 miRNAs were downreguleted and 13 were upregulated in response to B. elliptica. Moreover, based on the lily mRNA transcriptome, 22 targets for 9 known and 1 novel miRNAs were identified by the degradome sequencing approach. Most target genes for elliptica-responsive miRNAs were involved in metabolic processes, few encoding different transcription factors, including ELONGATION FACTOR 1 ALPHA (EF1a) and TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR 2 (TCP2). Furthermore, the expression patterns of a set of elliptica-responsive miRNAs and their targets were validated by quantitative real-time PCR. This study represents the first transcriptome-based analysis of miRNAs responsive to B. elliptica and their targets in lily. The results reveal the possible regulatory roles of miRNAs and their targets in B. elliptica interaction, which will extend our understanding of the mechanisms of this disease in lily.


Hepatic resection for metastatic colorectal cancer results in cure for some patients.
To determine the long-term disease-free and overall survivals for patients undergoing hepatic resection for colorectal cancer metastases and to define significant predictors of improved patients survival. Retrospective review. Single tertiary care center. Two hundred eighty consecutive patients underwent hepatic resection for colorectal cancer metastases at the Mayo Clinic from 1960 to 1987. Fifty patients alive at the completion of the study had a mean follow-up of 11.3 years (median, 121 months). Disease-free interval following initial hepatic resection and death. The overall 5-year survival of the 280 patients was 27%. Twenty-eight patients were alive at 10 years from the time of hepatic resection, and the 10-year actuarial survival was 20%. Only 2 patients alive and free of disease at 5 years had recurrent disease. For all other patients who were free of disease more than 5 years after hepatic resection and died, the cause of death was not cancer related. No patients characteristics or features of the primary tumor affected survival. Clinical presentation of metastatic disease, configuration of hepatic lesions, the presence of extrahepatic lymph node involvement, and the existence of resectable extrahepatic disease significantly affected long-term patient survival. Need for perioperative blood product transfusion was associated with a lower probability of long-term survival. Disease-free patient survival beyond 5 years from surgical resection of colorectal cancer metastases to the liver represents patient cure in nearly all instances.


Plasmacytoid dendritic cells mediate the regulation of inflammatory type T cell response for optimal immunity against respiratory Chlamydia pneumoniae infection.
Chlamydia pneumoniae (Cpn) infection is a leading cause for a variety of respiratory diseases and has been implicated in the pathogenesis of chronic inflammatory diseases. The regulatory mechanisms in host defense against Cpn infection are less understood. In this study, we investigated the role of plasmacytoid dendritic cells (pDCs) in immune regulation in Cpn respiratory tract infection. We found that in vivo depletion of pDCs increased the severity of infection and lung pathology. Mice depleted of pDC had greater body weight loss, higher lung bacterial burden and excessive tissue inflammation compared to the control mice. Analysis of specific T cell cytokine production pattern in the lung following Cpn infection revealed that pDC depleted mice produced significantly higher amounts of inflammatory cytokines, especially TNF-α, but lower IL-10 compared to the controls. In particular, pDC depleted mice showed pathogenic T cell responses characterized by inflammatory type-1 (CD8 and CD4) and inflammatory Th2 cell responses. Moreover, pDC depletion dramatically reduced CD4 regulatory T cells (Tregs) in the lungs and draining lymph nodes. Furthermore, pDC-T cell co-culture experiments showed that pDCs isolated from Cpn infected mice were potent in inducing IL-10 producing CD4 Tregs. Together, these findings provide in vivo evidence for a critical role of pDCs in homeostatic regulation of immunity during Cpn infection. Our findings highlight the importance of a 'balanced' immune response for host protective immunity and preventing detrimental immunopathology during microbial infections.


Assessment of bone healing in rabbit calvaria grafted with three different biomaterials.
This study evaluated the bone regeneration process in rabbit calvaria induced by three types of biomaterials: two xenogenous, consisting of deproteinized bovine bone, while the other was alloplastic, based on biphasic calcium phosphate. Five New Zealand white rabbits weighing between 2,900 and 3,500 g were submitted to four standard 8 mm-diameter perforations at the parietal bone. Three perforations were filled with three grafts and biomaterials, two of them received bovine Bio-Oss® and Endobon® Xenograft Granules, and the other consisted of fully alloplastic Straumann® Bone Ceramic. The fourth remaining cavity was used as control with coagulum. After eight weeks, the animals were sacrificed, and the samples were prepared for morphometric and qualitative analysis. The cavities filled with alloplastic biomaterials showed higher percentages of newly formed bone (p<0.05), while the cavities with xenogenous biomaterials showed higher amount of residual graft (p<0.05). Although the results showed greater bone formation with Straumann® Bone Ceramic, further studies are required to prove which is the more effective biomaterial for bone induction process.


Laryngeal sarcoidosis detected by FDG positron emission tomography.
Fluorodeoxyglucose positron emission tomography (FDG PET) has been widely used in the assessment of malignancy. However, FDG is not tumor-specific and may be taken up by nonmalignant conditions such as sarcoidosis. Sarcoidosis is a systemic disease and extrapulmonary lesions are also present. However, laryngeal sarcoidosis is a rare manifestation of extrapulmonary sarcoidosis. A 60-year-old man with a history of previous sarcoidosis presented with hoarseness. PET imaging demonstrated increased FDG uptake in the larynx. The histologic examination revealed laryngeal sarcoidosis. We report a case of laryngeal sarcoidosis and emphasize the role of FDG PET.


Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases.
GSK-3 is a ubiquitously expressed serine/threonine kinase existing as GSK-3α and GSK-3β isoforms, both active under basal conditions and inactivated upon phosphorylation by different upstream kinases. Initially discovered as a regulator of glycogen synthesis, GSK-3 is also involved in several signaling pathways controlling many different key functions. Here, we discuss recent advances regarding (i) GSK-3 structure, function, regulation, and involvement in several cancers, including hepatocarcinoma, cholangiocarcinoma, breast cancer, prostate cancer, leukemia, and melanoma (active GSK-3 has been shown to induce apoptosis in some cases or inhibit apoptosis in other cases and to induce cancer progression or inhibit tumor cell proliferation, suggesting that different GSK-3 modulators may address different specific targets); (ii) GSK-3 involvement in autophagy modulation, reviewing signaling pathways involved in neurodegenerative and liver diseases; (iii) GSK-3 role in oxidative stress and autophagic cell death, focusing on liver injury; (iv) GSK-3 as a possible therapeutic target of natural substances and synthetic inhibitors in many diseases; and (v) GSK-3 role as modulator of mammalian aging, related to metabolic alterations characterizing senescent cells and age-related diseases. Studies summarized here underline the GSK-3 multifaceted role and indicate such kinase as a molecular target in different pathologies, including diseases associated with autophagy dysregulation.


An N-terminal motif unique to primate tau enables differential protein-protein interactions.
Compared with other mammalian species, humans are particularly susceptible to tau-mediated neurodegenerative disorders. Differential interactions of the tau protein with other proteins are critical for mediating tau's physiological functions as well as tau-associated pathological processes. Primate tau harbors an 11-amino acid-long motif in its N-terminal region (residues 18-28), which is not present in non-primate species and whose function is unknown. Here, we used deletion mutagenesis to remove this sequence region from the longest human tau isoform, followed by glutathione S-transferase (GST) pulldown assays paired with isobaric tags for relative and absolute quantitation (iTRAQ) multiplex labeling, a quantitative method to measure protein abundance by mass spectrometry. Using this method, we found that the primate-specific N-terminal tau motif differentially mediates interactions with neuronal proteins. Among these binding partners are proteins involved in synaptic transmission (synapsin-1 and synaptotagmin-1) and signaling proteins of the 14-3-3 family. Furthermore, we identified an interaction of tau with a member of the annexin family (annexin A5) that was linked to the 11-residue motif. These results suggest that primate Tau has evolved specific residues that differentially regulate protein-protein interactions compared with tau proteins from other non-primate mammalian species. Our findings provide in vitro insights into tau's interactions with other proteins that may be relevant to human disease.


Sustainable Porous Carbon Materials Derived from Wood-Based Biopolymers for CO₂ Capture.
Porous carbon materials with tunable porosities and functionalities represent an important class of CO₂ sorbents. The development of porous carbons from various types of biomass is a sustainable, economic and environmentally friendly strategy. Wood is a biodegradable, renewable, sustainable, naturally abundant and carbon-rich raw material. Given these advantages, the use of wood-based resources for the synthesis of functional porous carbons has attracted great interests. In this mini-review, we present the recent developments regarding sustainable porous carbons derived from wood-based biopolymers (cellulose, hemicelluloses and lignin) and their application in CO₂ capture.


Near-infrared dye-conjugated amphiphilic hyaluronic acid derivatives as a dual contrast agent for in vivo optical and photoacoustic tumor imaging.
Amphiphilic hyaluronic acid (HA) derivatives bearing hydrophobic indocyanine green dye derivatives and hydrophilic poly(ethylene glycol) were synthesized through the use of condensation and copper-catalyzed click cyclization reactions. The amphiphilic HA derivatives dissolved in water and formed self-assemblies in which the near-infrared dyes were tightly packed and arranged to form dimers or H-aggregates. By irradiating an aqueous solution of HA derivatives with near-infrared light, photoacoustic signals were detected along with fluorescence emission. Self-assemblies consisting of HA derivatives could smoothly accumulate in tumor tissues by passive tumor targeting. By utilizing HA derivatives as a contrast agent, tumor sites were clearly visualized by optical imaging as well as by photoacoustic tomography.


Relationships among visual acuity, risk of acute myocardial infarction, and stroke: a nationwide cohort study in south korea.
Visual impairment (VI) is highly prevalent in the elderly and is associated with functional decline. Previous research demonstrated an association between VI and cardiovascular events, but investigations have yet to be conducted in general population samples. We evaluated the relationship between visual acuity (VA) and development of cardiovascular diseases (CVD) in a nationwide Korean population. This is a nationwide retrospective cohort study. We used the National Health Information Database of the National Health Insurance Service of Korea to identify subjects who participated in the National Health Insurance Service health screening program in 2012. We monitored 5,941,761 subjects for the development of cardiovascular diseases for a period of 5 years. After adjustments for age, sex, and other covariates, with subjects having a visual acuity better than 20/20 as the reference group, the adjusted hazard ratios (HRs) and 95% confidential intervals (CI) for acute myocardial infarction and stroke were visual acuity between 20/20 and 20/60, 1.073 (95% CI 1.053, 1.094) and 1.151 (95% CI 1.132, 1.171), respectively; for visual acuity between 20/60 and 20/200, 1.236 (95% CI 1.197, 1.277), and 1.336 (95% CI 1.302, 1.371), respectively; and for visual acuity worse than 20/200, 1.325 (95% CI 1.285, 1.366) and 1.383 (95% CI 1.349, 1.418), respectively. Subjects with lower VA had higher risks of acute myocardial infarction and stroke. These results suggest that low VA is an independent risk factor for CVD.


Entry-into-humans study with tezosentan, an intravenous dual endothelin receptor antagonist.
The purpose of this study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of tezosentan, an IV dual endothelin receptor antagonist, during first administration in humans. Tezosentan infused at doses of 5, 20, 50, 100, 200, 400, and 600 mg for 1 h was administered to sequential groups of six male subjects in a randomized, placebo-controlled, double-blind design. Recording of vital signs, electrocardiogram, adverse events, and clinical laboratory parameters monitored tolerability and safety. Blood samples were collected frequently for pharmacokinetic determinations and measurement of plasma endothelin-1 concentrations. Tezosentan was well tolerated at all dose levels. Headache was the most frequently reported adverse event and occurred at a higher incidence than with placebo at doses of > or = 100 mg. No clinically relevant changes in vital signs, electrocardiographic, or clinical laboratory parameters occurred. Plasma concentrations of tezosentan rapidly approached steady state and could be described by a two-compartment model. The volume of distribution at steady state (approximately 16 l) and the clearance (approximately 30 l/h) were considered independent of dose, in view of the wide dose range explored. A pronounced and rapid disposition phase (half-life 6 min), accounting for the major part of the elimination, was followed by a slower phase (half-life 3 h), probably caused by distribution from tissues. Endothelin-1 concentrations increased in a dose- and concentration-dependent fashion and returned slowly to baseline after termination of the infusion. Tezosentan warrants further clinical development in view of its tolerability and pharmacokinetic profile, which appears advantageous for application in emergency situations.


Mitochondrial DNA sequence of the hybrid of Takifugu flavidus (♀) × Takifugu rubripes (♂).
The complete mitochondrial genome of the hybrid of Takifugu flavidus (♀) × Takifugu rubripes (♂) was sequenced and characterized. The total length of the mitogenome is 16,443 bp. It contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 non-coding regions: origin of light-strand replication (OL) and control region (D-loop). The overall nucleotide composition of the heavy strand is 30.05% A, 25.79% T, 15.07% G and 29.09% C, with an A + T content of 55.84%. Except for ND6 gene and eight tRNA genes, other genes are encoded on the heavy strand. The complete mitogenome of the hybrid of T. flavidus (♀) × T. rubripes (♂) should contribute to further studies on mitochondrial inheritance mechanism.


Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on Imatinib at Two Dose Levels.
Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued. Median age was 60 years (range, 18 to 91 years). Median follow-up time was 10.9 years. Median progression-free survival times were 1.7 and 2.0 years in the 400- and 800-mg arms, respectively (hazard ratio, 0.91; P = .18), and median overall survival time was 3.9 years in both treatment arms. The estimated 10-year progression-free survival rates were 9.5% and 9.2% for the 400- and 800-mg arms, respectively, and the estimated 10-year overall survival rates were 19.4% and 21.5%, respectively. At multivariable analysis, age (< 60 years), performance status (0 v ≥ 1), size of the largest lesion (smaller), and KIT mutation (exon 11) were significant prognostic factors for the probability of surviving beyond 10 years. Conclusion This trial was carried out on a worldwide intergroup basis, at the beginning of the learning curve of the use of imatinib, in a large population of patients with advanced GIST. With a long follow-up, 6% of patients are long-term progression free and 13% are survivors. Among clinical prognostic factors, only performance status, KIT mutation, and size of largest lesion predicted long-term outcome, likely pointing to a lower burden of disease. Genomic and/or immune profiling could help understand long-term survivorship. Addressing secondary resistance remains a therapeutic challenge.


The effectiveness of bronchoscopy in the diagnosis of Pneumocystis carinii and cytomegalovirus pulmonary infections in acquired immunodeficiency syndrome.
We evaluated the sensitivity of bronchoscopy for the diagnosis of Pneumocystis carinii and cytomegalovirus pulmonary infections in patients with acquired immunodeficiency syndrome. The antemortem and postmortem diagnoses were compared in 36 patients who underwent fiberoptic bronchoscopy within two weeks of death. In autopsy-proved cases of Pneumocystis carinii pneumonia (PCP), the organism was correctly identified antemortem in 22 (88%) of 25 cases, including 94% of adequate transbronchial bronchoscopic biopsy specimens, 95% and 88% of bronchoalveolar lavage (BAL) cell blocks and smears, respectively, and 79% of brushing. In 11 patients who underwent simultaneous adequate biopsy, BAL, and brushings, the diagnostic sensitivity for PCP was 100%. The negative predictive value of bronchoscopy for PCP was 85%. Bronchoscopy yielded the diagnosis of cytomegalovirus infection in only 55% of autopsy-proved cases. Diagnostic sensitivity was also reduced when an important diagnostic procedure, such as transbronchial biopsy or BAL, was inadequate or not performed.


Zygomatic Rotation-Advancement: A New Concept for the Correction of Exorbitism in Patients With Syndromic Craniosynostosis.
The exophthalmos and class III malocclusion seen in Crouzon syndrome can be treated by Le Fort III advancement/distraction. However, reconstructive options for zygomatic retrusion are limited. The authors describe the repair of isolated exorbitism in a patient with Crouzon syndrome, via bilateral zygomatic rotation-advancement. A 34-year-old woman with Crouzon syndrome complained of exorbitism and malar hypoplasia. Four years prior, she declined Le Fort III advancement and underwent orthodontic/orthognathic correction of malocclusion. Radiographs were used to develop a computerized surgical plan. Bilateral periorbital osteotomy with advancement/rotation of the zygomatic process was performed using custom osteotomy guides and plates. Images obtained immediately postoperative and 3- and 19-month postoperative were compared to assess surgical stability, accuracy, and soft tissue changes. Decreased globe exposure and increased malar prominence have improved facial balance. Superimposed pre- and postoperative radiographs demonstrate bilateral advancement of the zygomatic body and inferior orbital rim. Superimposition of immediate postoperative and 19-month radiographs showed no relapse. Soft tissue histogram showed increased prominence of the malar eminence, lateral orbital rim, and cheek. Zygomatic rotation-advancement proved a safe, effective, stable, and predictable treatment for isolated malar hypoplasia in a patient with Crouzon syndrome. Virtual planning can enhance novel complex craniofacial procedures.


[Disturbed respiratory cycle accompanying hypoxic-ischemic encephalopathy].
We report the case of a 2-year-old boy who experienced total asphyxia at 4 months of age, and suffered abnormalities at specific phases of the respiratory cycle. The patient was bedridden due to severe tetraplegia and showed little response to external stimuli. He has been tube-fed since the initial asphyxia and a tracheotomy was performed after recurrent hypoxic episodes as a result of the respiratory dysfunction. Upon examination, his respiratory pattern was characterized by arrest during the inspiratory phase with a possible over-riding secondary inspiration. The respiratory pause at the inspiratory phase was markedly prolonged during an episode of pulmonary infection, resulting in recurrent cyanosis that necessitated artificial ventilation. The "second" inspiration typically occurred during the mid- or late-inspiratory phases, with this pattern often shown to be variable after epileptic seizures. The characteristic breathing of this patient suggested that difficulty in forming a normal respiratory cycle, other than during periods of hypoventilation or apnoea, could be a significant respiratory dysfunction following asphyxiation. Strategies for the management of such patients should be carefully designed after close observation of breathing patterns within the respiratory cycle, and with consideration for the influence of epileptic seizures and other inputs from somatic afferents.


Assessment of material loss of retrieved magnetically controlled implants for limb lengthening.
We aimed to understand wear from the telescopic component of PRECICE nails, which are used for distraction osteogenesis of the femur or tibia. We also aimed to identify any correlation between implant performance and patient factors. This retrieval study involved 11 magnetically controlled intramedullary nails from nine patients who had achieved the targeted leg length. All the nails were assessed macroscopically and microscopically for wear. All implants were radiographed to assess the internal mechanism. A Talyrond 365 (Taylor Hobson, Leicester, UK) roundness measuring machine was used to generate three-dimensional surface maps of the telescopic components to allow for measurement of wear. Visual assessment of all the nails showed evidence of wear from the telescopic component. The radiographs revealed that all the nails had intact internal mechanism and no evidence of fractured pins. The roundness measuring machine showed that the quantity of wear was lowest in the latest design of the PRECICE nail. There was no significant correlation between wear and the two patient factors (duration of the lengthening phase, the time of implantation) included in this study. This study is the first to investigate the performance of the three different designs of the PRECICE system with a focus on wear. We found that the latest design had the best implant performance. We are confident of the continued success of the PRECICE system and reassure surgeons and patients that they are unlikely to encounter problems with the implant related to wear.


Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.
Histamine H3 receptors are widely distributed Gi-coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H3-modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons.


An assessment of the overlap between morale and work engagement in a nonoperational military sample.
The degree of overlap between two positive motivational constructs-morale and work engagement-was assessed in a random sample of Canadian Armed Forces personnel stationed across Canada (N = 1,224). Based on self-determination theory and past research, job-specific self-efficacy, trust in teammates, and job significance were expected to be associated with morale and work engagement. Structural equation modeling analyses revealed that morale and work engagement were highly positively correlated, but had different patterns of association with predictor and outcome variables. Although trust in teammates and job significance predicted both morale and work engagement, job-specific self-efficacy predicted morale but not work engagement. Willingness to deploy on operations, turnover intentions, and psychological distress were predicted by both morale and work engagement, but morale was a better predictor of psychological distress and work engagement was a stronger predictor of turnover intentions. Together, the results suggest that, despite their overlap, morale and work engagement, as defined and measured herein, are not interchangeable.


Preoperative haemodynamic evaluation of patients submitted for renal artery stenosis.
The ECG, chest x-ray and haemodynamic parameters were investigated preoperatively in 19 patients subjected to surgery for renal artery stenosis (RAS) and in a control group comprising 19 normotensive patients subjected to other forms of major vascular surgery. Increased cardiac volume was demonstrated in 13 (68%) RAS patients and in two (11%) patients from the control group. Abnormal ECG (i.e. left ventricular hypertrophy or atrial fibrillation) was observed in 11 (58%) RAS patients and in one (5%) patient from the control group. In the RAS patients the following haemodynamic parameters were found to be statistically significantly increased, compared to the control group: systemic blood pressure, (systolic arterial pressure: +43%, diastolic arterial pressure: +38%, mean arterial pressure: +41%), pulmonary artery mean pressure (+64%), pulmonary capillary wedge pressure (+107%), heart rate (+15%), systemic vascular resistance (+27%), left ventricular minute work index (+46%) and right ventricular minute work index (+67%). The presence of increased cardiac volume and abnormal ECG were more closely related to the level of the pathologically increased pulmonary artery mean and wedge pressures than to the systemic blood pressure or central venous pressure. A preoperative haemodynamic evaluation is recommended to determine the degree of heart failure in RAS patients with: left ventricular hypertrophy and increased cardiac volume, or atrial fibrillation.


Health Literacy: Readability of ACC/AHA Online Patient Education Material.
To determine whether the online patient education material offered by the American College of Cardiology (ACC) and the American Heart Association (AHA) is written at a higher level than the 6th-7th grade level recommended by the National Institute of Health (NIH). Online patient education material from each website was subjected to reading grade level (RGL) analysis using the Readability Studio Professional Edition. One-sample t testing was used to compare the mean RGLs obtained from 8 formulas to the NIH-recommended 6.5 grade level and 8th grade national mean. In total, 372 articles from the ACC website and 82 from the AHA were studied. Mean (±SD) RGLs for the 454 articles were 9.6 ± 2.1, 11.2 ± 2.1, 11.9 ± 1.6, 10.8 ± 1.6, 9.7 ± 2.1, 10.8 ± 0.8, 10.5 ± 2.6, and 11.7 ± 3.5 according to the Flesch-Kincaid grade level (FKGL), Simple Measure of Gobbledygook (SMOG Index), Coleman-Liau Index (CLI), Gunning-Fog Index (GFI), New Dale-Chall reading level formula (NDC), FORCAST, Raygor Readability Estimate (RRE), and Fry Graph (Fry), respectively. All analyzed articles had significantly higher RGLs than both the NIH-recommended grade level of 6.5 and the national mean grade level of 8 (p < 0.00625). Patient education material provided on the ACC and AHA websites is written above the NIH-recommended 6.5 grade level and 8th grade national mean reading level. Additional studies are required to demonstrate whether lowering the RGL of this material improves outcomes among patients with cardiovascular disease.


PARTHENOGENESIS IN THE TROPICAL GEKKONID LIZARD, NACTUS ARNOUXII (SAURIA: GEKKONIDAE).
As currently diagnosed, Nactus arnouxii includes unisexual and bisexual populations. The geographic distribution of each type was estimated by sex-ratio analysis of samples from southwestern Pacific islands. Males were absent from southern Vanuatu (excluding Aneityum), New Caledonia, and all islands to the east that have been sampled. Both types of populations appear to be present on Aneityum. Chromosome and protein analyses showed that the bisexual populations are highly polytypic and probably consist of more than one biological species. The unisexual N. arnouxii were diploid, highly heterozygous, and showed no genetic segregation. The absence of segregation suggests clonal reproduction, substantiating parthenogenesis. The high heterozygosity of the unisexuals indicates their origin through hybridization. One parent was genetically similar to the extant bisexual population from northern Vanuatu. The other parent has not been identified, but its genetic characteristics are predicted by phylogenetic analysis.


Documenting ancient DNA quality via alpha satellite amplification and assessment of clone sequence diversity.
C/G-->T/A nucleotide alterations have been shown to hamper the straightforward interpretation of mitochondrial DNA sequence data derived from ancient tissues. Attempting to characterise this finding with respect to nuclear DNA, we contrasted two established protocols: (i) an enzymatic repair of damaged DNA, thereby translating and closing nicks in the DNA, and (ii) the application of N-phenacylthiazolium bromide, which cleaves glucose-derived protein crosslinks, presumably derived from Maillard reactions. We used medieval human bones that were refractory to standard PCR procedures. Due to negligible presence of short tandem repeat loci and also mitochondrial sequences, the extracted ancient DNA needed a higher copy PCR system to yield amplification products. The chosen PCR target was specific alphoid repetitive DNA with an experimentally determined minimum of 1000 copies per haploid genome. Alphoid repeat segments were generated from both contemporary DNA and DNA extracts of two human skeletons dating from 450-600 AD (omitting uracil N-glycosylase pre-treatment of the extracted samples), and were subsequently cloned and sequenced. The sequences were evaluated for the number and type of nucleotide alterations noted after the different pre-treatments, and were compared to our alphoid consensus sequence generated from modern DNA. Both methods failed to reflect the expected 32% variability among single alphoid repeats (accounting for locus-specific differences and polymerase errors) as well as to display the actual 2.88 ratio of transitions to transversions. Our data obtained from high-copy-number nuclear DNA mirror the phenomenon of sequence deviations observed in mitochondrial DNA extracted from old specimens.


Medication Adherence Status and Its Association With Quality of Life Among Individuals With Neurological Conditions in Saudi Arabia.
Chronic disorders commonly require long-term therapies. Medication non-adherence can cause major morbidity and mortality in chronic illness individuals, as well as increase the financial burden on the healthcare system. It is considered that patients who adhere to their treatment may improve their quality of life (QoL). There is a scarcity of updated comprehensive data on medication adherence among Saudi patients with neurological disorders. Therefore, this study aimed to assess the medication adherence status among individuals with neurological conditions and its association with QoL. A cross-sectional questionnaire-based study was conducted. The study included subjects individuals who have neurological conditions aged at least 18 from different regions of Saudi Arabia. The questionnaire measured medication adherence by using the 10-item version of the Medication Adherence Report Scale (MARS-10, ©Professor Rob Horne). The QoL was measured by employing validated Euro Quality of Life 5-dimension scale (EQ-5D). A total of 370 participants were included. Respondents aged 18 to 35 years represented 62.4% of the sample. More than half of the participants were females (65.7%). The most frequently reported chronic conditions were migraine (29.2%), epilepsy (20.8%), and multiple sclerosis (20.5%). The reliability of the EQ-5D questionnaire was acceptable (Cronbach's alpha = 0.764). In general, more than half of the participants indicated that had problems due to pain/discomfort (60.3%) and anxiety/depression (62.2%). The most common pattern of non-adherence was taking the medication only when a patient needed it followed by avoiding taking the medication as possible. Non-adherence to medications was less prevalent among participants with epilepsy (68.8%) and multiple sclerosis (65.8%). On the other hand, medication adherence was higher among respondents with migraine compared to participants without the condition (86.1% vs 73.7%, p = 0.009). A significantly lower proportion of participants who had some or extreme problems with self-care were non-adherent to medications compared to those who had no problems (68.1% vs 80.3%, respectively, p = 0.016). Results of the regression analysis showed that participants with epilepsy and multiple sclerosis were less likely to be non-adherence to medications. Furthermore, respondents with moderate and severe problems in self-care were less likely to be non-adherent. It was found that more than half of the participants had problems regarding their QoL due to pain/discomfort and anxiety/depression. The most prevalent pattern of non-adherence was taking the medication only when needed. Participants with epilepsy and multiple sclerosis were less likely to be non-adherent to medications. Furthermore, respondents with moderate and severe problems in self-care were less likely to be non-adherent. We recommend serial studies on the issue should be conducted to gather more evidence regarding this topic.


Diploid sperm produced by artificially sex-reversed clone loaches.
Clone loaches reproduce unisexually in a wild population of Hokkaido Island, Japan. These clone loaches produce genetically identical unreduced eggs which develop to diploid individuals without any genetic contribution of sperm donors. In the present study, sex reversal of clone loaches was attempted and the reproductive potential of resultant clone males was examined. Clone loaches administered 0.5 ppm of 17-alpha methyltestosterone (MT) for 30 days from 1 month after hatching differentiated into physiological males. These sex-reversed clone males produced fertile spermatozoa with a diploid DNA content. Diploid spermatozoa had significantly larger heads than normal haploid sperm, but had a normal shape showing a head, mid-piece, and tail. The motility of diploid spermatozoa was low after ambient water was added. Concentration of diploid spermatozoa per unit of sperm was lower than that of control haploid spermatozoa. Microsatellite genotyping revealed that triploid progeny from the cross between a normal diploid female and a sex-reversed clone male had two alleles specific to the diploid clone male and one allele of the mother loach. These results indicated that the sex-reversed clone males produced fertile diploid spermatozoa genetically identical to the clone lineage.


Extracellular matrix fluctuations during early embryogenesis.
Extracellular matrix (ECM) movements and rearrangements were studied in avian embryos during early stages of development. We show that the ECM moves as a composite material, whereby distinct molecular components as well as spatially separated layers exhibit similar displacements. Using scanning wide field and confocal microscopy we show that the velocity field of ECM displacement is smooth in space and that ECM movements are correlated even at locations separated by several hundred micrometers. Velocity vectors, however, strongly fluctuate in time. The autocorrelation time of the velocity fluctuations is less than a minute. Suppression of the fluctuations yields a persistent movement pattern that is shared among embryos at equivalent stages of development. The high resolution of the velocity fields allows a detailed spatio-temporal characterization of important morphogenetic processes, especially tissue dynamics surrounding the embryonic organizer (Hensen's node).


Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas without detectable NR4A3 fusion genes.
Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal tumor cytogenetically characterized by reciprocal translocations, such as t(9;22)(q22;q12) and t(9;17)(q22;q11), which result in EWSR1/NR4A3 and TAF15/NR4A3 fusion genes (alias EWS/NOR1, TAF2N/NOR1), respectively. NOR1 is an orphan nuclear receptor and acts as a transcription factor that can bind to its putative coactivator, SIX3. Although the NOR1 fusion protein has been implicated in oncogenesis of EMC, a small fraction of EMC lacks detectable rearrangements of the NR4A3 gene or 9q22. We report a case of EMC with no detectable NR4A3 gene alterations, as assessed with various molecular techniques including reverse transcription-polymerase chain reaction (RT-PCR), Southern blotting, interphase fluorescence in situ hybridization, and PCR single-strand conformation polymorphism-but with coexpression of native NOR1 and SIX3. In our survey of another 18 EMCs, we identified one more case expressing both NOR1 and SIX3 but lacking NR4A3 fusion. Fourteen tumors with detectable NR4A3 fusion genes (EWSR1-NR4A3; TAF15-NR4A3) expressed neither native NOR1 nor SIX3. SIX3 expression is normally confined specifically to the developing eye and fetal forebrain, although the expression of NR4A3 is largely ubiquitous. Our data suggest that aberrant coexpression of NOR1 and SIX3 is a potential alternative mechanism underlying the development of EMC.


Advanced glycation endproducts increase proliferation, migration and invasion of the breast cancer cell line MDA-MB-231.
Diabetic patients have increased likelihood of developing breast cancer. Advanced glycation endproducts (AGEs) underlie the pathogenesis of diabetic complications but their impact on breast cancer cells is not understood. This study aims to determine the effects of methylglyoxal-derived bovine serum albumin AGEs (MG-BSA-AGEs) on the invasive MDA-MB-231 breast cancer cell line. By performing cell counting, using wound-healing assay, invasion assay and zymography analysis, we found that MG-BSA-AGEs increased MDA-MB-231 cell proliferation, migration and invasion through Matrigel™ associated with an enhancement of matrix metalloproteinase (MMP)-9 activities, in a dose-dependent manner. Using Western blot and flow cytometry analyses, we demonstrated that MG-BSA-AGEs increased expression of the receptor for AGEs (RAGE) and phosphorylation of key signaling protein extracellular signal-regulated kinase (ERK)-1/2. Furthermore, in MG-BSA-AGE-treated cells, phospho-protein micro-array analysis revealed enhancement of phosphorylation of the ribosomal protein 70 serine S6 kinase beta 1 (p70S6K1), which is known to be involved in protein synthesis, the signal transducer and activator of transcription (STAT)-3 and the mitogen-activated protein kinase (MAPK) p38, which are involved in cell survival. Blockade of MG-BSA-AGE/RAGE interactions using a neutralizing anti-RAGE antibody inhibited MG-BSA-AGE-induced MDA-MB-231 cell processes, including the activation of signaling pathways. Throughout the study, non-modified BSA had a negligible effect. In conclusion, AGEs might contribute to breast cancer development and progression partially through the regulation of MMP-9 activity and RAGE signal activation. The up-regulation of RAGE and the concomitant increased phosphorylation of p70S6K1 induced by AGEs may represent promising targets for drug therapy to treat diabetic patients with breast cancer.


Tumor Fraction Correlates With Detection of Actionable Variants Across > 23,000 Circulating Tumor DNA Samples.
Profiling of circulating tumor DNA (ctDNA) is increasingly adopted in the management of solid tumors, concurrent with increased availability of more comprehensive ctDNA panels. However, variable ctDNA shed can result in variable assay sensitivity. We studied the relationship between ctDNA tumor fraction (TF) and detection of actionable alterations across cancer types. A total of 23,482 liquid biopsies (LBx) submitted between September 2020 and October 2021 were sequenced using a hybrid capture panel that reports genomic alterations (GAs) and genomic biomarkers across 324 cancer-related genes. The primary end points were the prevalence of targetable GAs by cancer type and detection in relationship to ctDNA TF. Sensitivity of detection in LBx was assessed in 1,289 patients with available tissue results. 94% (n = 22,130) of LBx had detectable ctDNA, with a median TF of 2.2%. LBx profiling detected GAs in National Comprehensive Cancer Network category 1 genes in 37% of lung, 30% of prostate, 36% of breast, and 51% of colon cancer cases. Potential germline GAs flagged on clinical reports were detected in genes including BRCA1/2, PALB2, CHEK2, and ATM. Polyclonal mutations in genes associated with resistance such as AR, ESR1, RB1, and NF1 were detected. The sensitivity of LBx to detect driver alterations identified in tissue biopsy from the same patient ranged from 58% to 86% but was consistently at or near 100% in cases with TF ≥ 10%. Elevated ctDNA shed is associated with both high sensitivity and negative predictive value for detection of actionable GAs. The presence of elevated TF suggests adequate tumor profiling and may reduce the value of subsequent reflex to confirmatory tissue testing in patients with negative LBx results.


The mediatory role of medication adherence in improving patients' medication experience through patient-physician communication among older hypertensive patients.
Understanding how patient-physician communication affects patients' medication experience would help hypertensive patients maintain their regular long-term medication therapy. This study aimed to examine whether patient-physician communication (information and interpersonal treatment) affects patients' medication experience directly or indirectly through changing medication adherence for each of the two communication domains. A self-administered cross-sectional survey was conducted for older patients who had visited a community senior center as a member. Two communication domains were assessed using two subscales of the Primary Care Assessment Survey. Medication adherence and experience were measured using the Morisky Medication Adherence Scale and a five-point Likert scale, respectively. Mediatory effects were assessed via Baron and Kenny's procedure and a Sobel test. Patient-physician communication had a positive prediction on patients' medication experience (β=0.25, P=0.03), and this was fully mediated by medication adherence (z=3.62, P<0.001). Of the two components of patient-physician communication, only informative communication showed a mediatory effect (z=2.21, P=0.03). Patient-physician communication, specifically informative communication, had the potential to improve patients' medication experience via changes in medication adherence. This finding can inform health care stakeholders of the mediatory role of medication adherence in ensuring favorable medication experience for older hypertensive patients by fostering informative patient-physician communication.


Harmony and Distress: Humor, Culture, and Psychological Well-Being in South Korean Organizations.
Humor is a contextual phenomenon that exists in all societies, although the impact of humor may differ across different cultures. The data for this research was collected using an ethnographic-based approach, incorporating participant observation and semi-structured interviews. Based in three different South Korean organizations, this research offered the opportunity to interact in depth with workers of varying ages, genders, hierarchical levels, and organizational roles. Humor styles incorporate both light and dark forms of humor that may be affiliative and self-enhancing or aggressive and detrimental or may contain elements from both styles simultaneously Observations were complimented by 46 in-depth interviews and ad hoc follow-up discussions. This paper adopts a Confucian perspective to understand the perception and use of workplace humor in these South Korean organizations. Confucian philosophy emphasizes the value of formality within society in order to maintain respectful relationships between individuals. We suggest that humor is used in these South Korean workplaces to support traditional Confucian values of harmony and hierarchy, and the changing cultural values in these workplaces influence humor perceptions in complex ways. The Confucian value of harmony maintained through the idea of hierarchy creates pressure for organizational members, to accept and cope with contentious humor in the workplace. In particular, the clash between the need to maintain harmonious relationships in the workplace (through obedience toward superiors) and the desire to reject some types of humor highlights issues for younger organizational members. Internal conflict creates distress for younger employees who may hold more Westernized values and this affects their emotional, psychological well-being. This study presents a cross-cultural perspective to organizational humor, and suggests that humor may not always be a positive experience for organizational members, but instead may create psychological distress in some employees.


Uncovering the Protective Mechanism of the Volatile Oil of Acorus tatarinowii against Acute Myocardial Ischemia Injury Using Network Pharmacology and Experimental Validation.
Acorus tatarinowii is a traditional aromatic resuscitation drug that can be clinically used to prevent cardiovascular diseases. The volatile oil of Acorus tatarinowii (VOA) possesses important medicinal properties, including protection against acute myocardial ischemia (MI) injury. However, the pharmacodynamic material basis and molecular mechanisms underlying this protective effect remain unclear. Using network pharmacology and animal experiments, we studied the mechanisms and pathways implicated in the activity of VOA against acute MI injury. First, VOA was extracted from three batches of Acorus tatarinowii using steam distillation, and then, its chemical composition was determined by GC-MS. Next, the components-targets and protein-protein interaction networks were constructed using systematic network pharmacology. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted in order to predict the possible pharmacodynamic mechanisms. Furthermore, animal experiments including ELISAs, histological examinations, and Western blots were performed in order to validate the pharmacological effects of VOA. In total, 33 chemical components were identified in VOA, and ß-asarone was found to be the most abundant component. Based on network pharmacology analysis, the therapeutic effects of VOA against myocardial ischemia might be mediated by signaling pathways involving COX-2, PPAR-α, VEGF, and cAMP. Overall, the obtained results indicate that VOA alleviates the pathological manifestations of isoproterenol-hydrochloride-induced myocardial ischemia in rats, including the decreased SOD (superoxide dismutase) content and increased LDH (lactic dehydrogenase) content. Moreover, the anti-MI effect of VOA might be attributed to the downregulation of the COX-2 protein that inhibits apoptosis, the upregulation of the PPAR-α protein that regulates energy metabolism, and the activation of VEGF and cAMP signaling pathways.


The emergence and consolidation of self-control from eighteen to thirty months of age: normative trends and individual differences.
This study is a descriptive report of the capability to exercise self-control in very young children. 2 aspects of self-control were assessed (delay/response inhibition in the presence of an attractive stimulus and compliance with maternal directives in a cleanup task) for 72 children between the ages of 18 and 30 months. The results indicated that both aspects of self-control show age-related increases. However, a factor analysis of the behaviors observed in the cleanup task suggested that compliance could not be adequately described with a unitary, bipolar dimension (noncompliance vs. compliance). 2 patterns of non-compliance were observed, and 1 of these also increased with age. Cross-task consistency for the delay measures) and coherence across the 2 aspects of self-control showed a positive relationship with increasing age. Finally, correlational analyses of the self-control measures and developmental test data showed that individual differences in self-control were associated with differences in cognitive-developmental status (DA). The results are interpreted as evidence that the achievement of self-control can be considered as a major developmental accomplishment and as evidence that individual differences in self-control emerge and are consolidated during the second and third years of life.


6Li MAS NMR spectroscopy and first-principles calculations as a combined tool for the investigation of Li2MnSiO4 polymorphs.
Polymorphism of Li(2)MnSiO(4) was inspected by (6)Li MAS NMR spectroscopy. The detected isotropic shifts and spinning-sideband patterns were successfully reproduced by first-principles calculations and offered an insight into structural differences among the polymorphs. The approach for predicting isotropic shifts was also tested on several other Li-containing paramagnetic structures.


The effect of simulated flash heating pasteurisation and Holder pasteurisation on human milk oligosaccharides.
Human milk oligosaccharides (HMOs) have important protective functions in human milk. A low-cost remote pasteurisation temperature-monitoring system has been designed using FoneAstra, a cell phone-based networked sensing system to monitor simulated flash heat pasteurisation. To compare the pasteurisation effect on HMOs of the FoneAstra FH method with the current Sterifeed Holder method used by human milk banks. Donor human milk samples (n = 48) were obtained from a human milk bank and pasteurised using the two pasteurisation methods. HMOs were purified from samples and labelled before separation using high-performance liquid chromatography. Concentrations of total HMOs, sialylated and fucosylated HMOs and individual HMOs using the two pasteurisation methods were compared using repeated-measures ANOVA. The study demonstrated no difference in total concentration of HMOs between the two pasteurisation methods and a small but significant increase in the total concentration of HMOs regardless of pasteurisation methods compared with controls (unpasteurised samples) (p<0.0001). The FoneAstra FH pasteurisation system does not negatively affect oligosaccharides in human milk and therefore is a possible alternative for providing safely sterilised human milk for low- and middle-income countries.


Emergence of Vibrio parahaemolyticus as an important cause of diarrhea in Malaysia.
Vibrio parahaemolyticus was isolated from 47 of 2,699 stools examined primarily for the exclusion of cholera. All strains grew well in alkaline peptone water containing 0.5% NaCl and in Monsur's medium. Serotyping showed them to be of various types. Adults were mainly affected. The importance of looking for V. parahaemolyticus in clinical specimens from cases of diarrhea is emphasized.


π-stacking and C-X...D (X = H, NO2; D = O, π) interactions in the crystal network of both C-H...N and π-stacked dimers of 1,2-bis(4-bromophenyl)-1H-benzimidazole and 2-(4-bromophenyl)-1-(4-nitrophenyl)-1H-benzimidazole.
Molecules of 1,2-bis(4-bromophenyl)-1H-benzimidazole, C19H12Br2N2, (I), and 2-(4-bromophenyl)-1-(4-nitrophenyl)-1H-benzimidazole, C19H12BrN3O2, (II), are arranged in dimeric units through C-H...N and parallel-displaced π-stacking interactions favoured by the appropriate disposition of N- and C-bonded phenyl rings with respect to the mean benzimidazole plane. The molecular packing of the dimers of (I) and (II) arises by the concurrence of a diverse set of weak intermolecular C-X...D (X = H, NO2; D = O, π) interactions.


[Spontaneous ruptures of the urinary bladder in the routine forensic examination].
This article analyses three cases of death following a spontaneous rupture of the urinary bladder. One case is based on an extensive tamponade of the bladder eight days after a transurethral resection of the prostate gland. Two other cases of death by spontaneous rupture resulted from increased alcohol consumption. The paper presents an overview of pathomorphological findings such as the typical intraperitoneal rupture localisation at the posterior wall of the urinary bladder or bladder dome and the subsequent diagnosed causes of death. In addition predisposing (anamnestic) influencing factors such as chronic alcoholism are highlighted and their relevance for the clinical urologist and the forensic pathologist are discussed.


[Effect of high-iodine intake on MBP mRNA expression in cerebrum of filial mice and selenium intervention].
To study the effect of selenium supplementation on myelin basic protein (MBP) mRNA expression in cerebrum of high-iodine intake filial mice. 135 weanling female Balb/C mice were assigned into 3 groups and given drinking water including different doses of iodine and selenium. Normal control (NC, tap water), high iodine intake group (HI, 3.0 mg/L I of drinking water), high iodine intake and selenium supplementation group I (HI + Se, 3.0 mg/L I + 0.5 mg/L Se of drinking water). All the male and female mice were mated after 4 months later, related indicators of filial mice on 14 day were determined. In filial mice, compared with NC group, serum TT4 decreased significantly in HI groups, TT3 also decreased, and mRNA expression of MBP in cerebrum was down-regulated 27%. The selenium suppleme ntation groups inhibited the decrease of TT4 and TT3, up regulated the m RNA expression of MBP in cerebrum. High-iodine Intake can decrease thyroxine of filial mice, which maybe is the reason for down-regulated m RNA expression of MBP in cerebrum, and selenium can exert some intervention by thyroxine, but need to verify more.


A study on enterobiasis among aboriginal children in Nanao and Tatung districts, Ilan county, northeast Taiwan.
From May 1981 to March 1984, consecutive surveys with Scotch tape perianal swab for enterobiasis were conducted among school children in 8 primary schools in the Nanao District, also involved were 1 junior high and 8 primary schools from the Tatung District, Ilan County, Northeast Taiwan. Field treatments with mebendazole (10 mg) or albendazole (400 mg) were also conducted following 9 periods of screening for pinworm. Prior to treatment, the infection rates in Nanao and Tatung were 14.1% and 8.3%, respectively. These rates were reduced to 0.4% and 1.1% by March 1984, respectively. Throughout the study, significantly higher infection rates were generally found during the months of September, November, and December and lower rates were obtained in June. There was no difference between the infection rates of aboriginal school boys and girls. The results of the present study indicate that monthly chemotherapy is the best method for controlling pinworm infections in these mountainous regions.


Antioxidant activity and diffusion of catechin and epicatechin from antioxidant active films made of poly(L-lactic acid).
Active membranes and food packaging containing antioxidants like catechin and epicatechin, combined with the use of materials made of biopolymers obtained from renewable sources, could create a novel alternative to reduce oxidation in food, pharmaceutical, and cosmetic products. Poly(94% L-lactic acid) films containing 1.28% catechin and 1.50% epicatechin were extruded in a pilot plant-scale extrusion machine. The diffusion kinetics of catechin and epicatechin into 95% ethanol at 20, 30, 40, and 50 °C and 50% ethanol at 40 °C displayed Fickian release behavior and diffusion coefficients between 0.5 and 50 × 10(-11) cm(2)/s. According to the Arrhenius equation, the energy of activation for the diffusion of catechin and epicatechin in the films was 110.43 and 98.92 kJ/mol, respectively. The antioxidant activity of the films was measured in methanol extracts containing 46.42 μg/mL of catechin and 57.52 μg/mL of epicatechin as 32.90 and 36.68% of scavenging the 2,2-diphenyl-1-picrylhydrazyl radical, respectively.


MicroRNAs that target Ca(2+) transporters are involved in vascular smooth muscle cell calcification.
The role of microRNAs (miRNAs) in vascular calcification is currently unclear. To examine how miRNAs are involved in vascular smooth muscle cell (VSMC) calcification, we explored the alteration of miRNAs in VSMC calcification in vitro and in vivo. Klotho homozygous mutant mice (kl/kl) display vascular calcification and have perturbations of calcium handling. We therefore hypothesized that the calcium perturbations in VSMCs could be mediated by miRNAs. Using an miRNA array analysis, we demonstrated that miRNAs are aberrantly expressed in the aortic media of 3-week-old kl/kl mice compared with wild-type (WT) mice. The expression levels of miR-135a(*), miR-762, miR-714, and miR-712(*) in the aortic media of kl/kl mice were significantly higher than in WT mice. We used quantitative real-time reverse transcriptase polymerase chain reaction to further confirm that these miRNAs were increased in the aortic media of kl/kl mice and in cultured VSMCs treated with high phosphate and calcium. A search of the miRNA database indicated that the Ca(2+) efflux proteins NCX1, PMCA1, and NCKX4 frequently appeared as potential targets of these miRNAs. The transfection of miRNA mimics into cultured VSMCs reduced the protein levels of each potential target. Conversely, miRNA inhibitors reduced phosphate and calcium-induced VSMC calcification. Furthermore, these inhibitors decreased the intracellular Ca(2+) concentration in cultured VSMCs after treatment with phosphate and calcium. Our results suggest that increased expression of miR-135a(*), miR-762, miR-714, and miR-712(*) in VSMCs may be involved in VSMC calcification by disrupting Ca(2+) efflux proteins.


Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index.
The purpose of the study is to describe early predictors and to develop a prediction tool that accurately identifies the need for mechanical ventilation (MV) in pneumonia patients with hypoxemic acute respiratory failure (ARF) treated with high-flow nasal cannula (HFNC). This is a 4-year prospective observational 2-center cohort study including patients with severe pneumonia treated with HFNC. High-flow nasal cannula failure was defined as need for MV. ROX index was defined as the ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate. One hundred fifty-seven patients were included, of whom 44 (28.0%) eventually required MV (HFNC failure). After 12 hours of HFNC treatment, the ROX index demonstrated the best prediction accuracy (area under the receiver operating characteristic curve 0.74 [95% confidence interval, 0.64-0.84]; P<.002). The best cutoff point for the ROX index was estimated to be 4.88. In the Cox proportional hazards model, a ROX index greater than or equal to 4.88 measured after 12 hours of HFNC was significantly associated with a lower risk for MV (hazard ratio, 0.273 [95% confidence interval, 0.121-0.618]; P=.002), even after adjusting for potential confounding. In patients with ARF and pneumonia, the ROX index can identify patients at low risk for HFNC failure in whom therapy can be continued after 12 hours.


[Update on the treatment of sarcoidosis].
Sarcoidosis is a granulomatous disease characterized by variable manifestations and course. About 50% of patients will require systemic treatment, while the remaining will present spontaneous resolution of the disease. When a systemic therapy is necessary, it is prolonged and relapse rate is high when it is discontinued. Systemic corticosteroids are the first line treatment in sarcoidosis. Because of many side effects, it is essential to consider other drugs in case of intolerance to steroids, as steroid-sparing agents, or in case of inefficiency of corticotherapy alone.


[Impact of an information campaign on cardiovascular risk factors. 5-year results at the study town Epernon].
Information campaigns are implemented to improve knowledge of cardiovascular disease and risk factors. The impact of these programs must be evaluated to determine whether they truly contribute to modifying risk factors in the population. A 5-year information campaign on cardiovascular disease and risk factors was conducted in Epernon, France. The main objectives of the campaign focused on stopping smoking, regular physical exercise and balanced nutrition. Data were collected from a representative sample of the female and male population aged 20 to 65 years selected from the study town Epernon (500 subjects), and in control towns, Magny-en-Vexin and Moret-sur-Loing (200 subjects). The study town and control towns were comparable for population, demographic characteristics and geographic localization (distance from Paris). The subjects were invited to respond to a questionnaire on demographic data, attitudes toward health, risk factors and diet and underwent a clinical examination with blood tests. The initial sample included 961 subjects and 68.5% participated in the final survey. We were unable to evidence any significant difference in risk factors or the 10-year risk score calculated from the Framingham equation adapted to France. The information campaign was well accepted, the population not expression a feeling of lassitude. The campaign had a minimal effect on the way individuals relate to health. There was a fall in mean energy intake, mainly fat calories, which was similar in all three towns. No major modification in cardiovascular risk factors was observed in this low-risk population, suggesting that future information campaigns should be aimed at targeted populations with a higher risk profile using simple and selected messages.