Nasal challenge testing in grass pollen hay fever.
Nasal sensitivity to rye grass pollen allergens was evaluated by provocation testing in patients with hay fever due to grass pollen using measurements of nasal airways resistance (NAR), a reproducible system for delivery of allergen, and stringent criteria for allergen storage. Reproducibility was assessed in 24 subjects with hay fever by nasal provocation with serial dilutions of Lolium perenne allergens on 3 occasions: during the grass pollen season, immediately after the season, and in early winter. Threshold doses of allergen required to double the saline control NAR or to provoke persistent sneezing and rhinorrhea were slightly higher 1 mo after the pollen season, but there was no significant differences between threshold doses during the pollen season and 8 mo later. When the threshold doses during challenges were exceeded, there were late reactions in 4 of 24 patients. Normal subjects and patients with perennial rhinitis and with negative skin tests to L. perenne extract were unresponsive in nasal challenge tests.


Mapping neural circuits with activity-dependent nuclear import of a transcription factor.
Abstract: Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method-CaLexA (calcium-dependent nuclear import of LexA)-for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals.


Mycobacterium ulcerans disease, Peru.
Eight adult patients (ages 18-58, 5 women) with Buruli ulcer (BU) confirmed by at least 2 diagnostic methods were seen in a 10-year period. Attempts to culture Mycobacterium ulcerans failed. Five patients came from jungle areas, and 3 from the swampy northern coast of Peru. The patients had 1-5 lesions, most of which were on the lower extremities. One patient had 5 clustered gluteal lesions; another patient had 2 lesions on a finger. Three patients were lost to follow-up. All 5 remaining patients had moderate disease. Diverse treatments (antituberculous drugs, World Health Organization [WHO] recommended antimicrobial drug treatment for BU, and for 3 patients, excision surgery) were successful. Only 1 patient (patient 7) received the specific drug treatment recommended by WHO. BU is endemic in Peru, although apparently infrequent. Education of populations and training of health workers are first needed to evaluate and understand the full extent of BU in Peru.


[Diagnostic value of endoscopic ultrasonography for submucosal tumors of upper gastrointestinal tract].
To evaluate the diagnostic value of endoscopic ultrasonography (EUS) for submucosal tumors (SMTs) of upper gastrointestinal tract. A retrospective analysis was made based on clinical data of 206 upper gastrointestinal SMTs patients from January 2009 to July 2013 in The First Affiliated Hospital of Soochow University. Preoperative EUS findings were compared with postoperative pathological diagnosis, and the sensitivity, specificity and accuracy of EUS diagnosis in property and layer origin of SMTs were calculated. The sensitivity, specificity and accuracy of EUS diagnosis in SMTs property were 60.2%, 67.1% and 61.2%. The sensitivity, specificity and accuracy of EUS diagnosis in layer origin of SMTs were 98.0%, 98.2% and 98.1%. EUS has limited value in the diagnosis of property of SMT, and has high accuracy of identifying the origin layer, which is helpful to choose therapeutic schedule of SMT under endoscopy.


Associations between maternal social support and stressful life event with ventricular septal defect in offspring: a case-control study.
Previous studies suggested that maternal subjective feeling of stress seemed to be involved in the incidence of congenial heart disease in offspring. To better understand the findings, our study would discuss the relationships of maternal exposure to stressful life event and social support, which are more objective and comprehensive indicators of stress, around periconceptional period with the risk of ventricular septal defect (VSD), the most popular subtype of congenital heart disease. A hospital-based case-control study was conducted through June, 2016 to December, 2017. We collected maternal self-reports of 8 social support questions in 3 aspects and 8 stressful life events among mothers of 202 VSD cases and 262 controls. Social support was categorized into low, medium high, and high (higher is better), and stressful life event was indexed into low, medium low, and high (higher is worse). Logistic regression models were applied to estimate adjusted odds ratios and 95% confidence intervals (95% CI). The adjusted odds ratio of high stressful life event was 2.342 (95% CI: 1.348, 4.819) compared with low stressful life event. After crossover analysis, compared with low event & high support, the adjusted odds ratio of low event & low support, high event & high support, and high event & low support were 2.059 (95% CI: 1.104, 3.841), 2.699 (95% CI: 1.042, 6.988) and 2.781 (95% CI: 1.033, 7.489), respectively. In summary, we observed an increased risk of VSD when pregnant women exposed to stressful life events, however, social support could, to some extent, reduce the risk of stressful life event.


Photoaffinity labeling of the tetracycline binding site of the Escherichia coli ribosome. The uses of a high intensity light source and of radioactive sancycline derivatives.
[3H]Tetracycline (TC) has been shown to photoincorporate into the Escherichia coli ribosome. However, the utility of this process for characterizing the TC binding site on the ribosome is diminished by competing side reactions which also lead to incorporation of radioactivity. In this work we first conducted a detailed study of the labeling processes occurring when ribosomes are irradiated in the presence of [3H]TC with a common, rather low intensity, lamp. On the basis of the results of this study we next explored the usefulness for photoaffinity labeling of the TC site of both irradiation with a high-intensity laser and radioactive, functional TC derivatives having different photochemical properties than TC itself. Labeling patterns determined by polyacrylamide gel electrophoretic analysis of ribosomal proteins extracted from photoaffinity-labeled 30S subunits provided strong evidence that these two approaches offer distinct advantages for characterizing the TC binding site.


Fission-fusion dynamics in the social networks of a North American pitviper.
Many animal species exist in fission-fusion societies, where the size and composition of conspecific groups change spatially and temporally. To help investigate such phenomena, social network analysis (SNA) has emerged as a powerful conceptual and analytical framework for assessing patterns of interconnectedness and quantifying group-level interactions. We leveraged behavioral observations via radiotelemetry and genotypic data from a long-term (>10 years) study on the pitviper Crotalus atrox (western diamondback rattlesnake) and used SNA to quantify the first robust demonstration of social network structures for any free-living snake. Group-level interactions among adults in this population resulted in structurally modular networks (i.e., distinct clusters of interacting individuals) for fidelis use of communal winter dens (denning network), mating behaviors (pairing network), and offspring production (parentage network). Although the structure of each network was similar, the size and composition of groups varied among them. Specifically, adults associated with moderately sized social groups at winter dens but often engaged in reproductive behaviors-both at and away from dens-with different and fewer partners. Additionally, modules formed by individuals in the pairing network were frequently different from those in the parentage network, likely due to multiple mating, long-term sperm storage by females, and resultant multiple paternity. Further evidence for fission-fusion dynamics exhibited by this population-interactions were rare when snakes were dispersing to and traversing their spring-summer home ranges (to which individuals show high fidelity), despite ample opportunities to associate with numerous conspecifics that had highly overlapping ranges. Taken together, we show that long-term datasets incorporating SNA with spatial and genetic information provide robust and unique insights to understanding the social structure of cryptic taxa that are understudied.


Brucella pathogenesis, genes identified from random large-scale screens.
Pathogenicity islands, specialized secretion systems, virulence plasmids, fimbriae, pili, adhesins, and toxins are all classical bacterial virulence factors. However, many of these factors, though widespread among bacterial pathogens, are not necessarily found among bacteria that colonize eukaryotic cells in a pathogenic/symbiotic relationship. Bacteria that form these relationships have developed other strategies to infect and grow in their hosts. This is particularly true for Brucella and other members of the class Proteobacteria. Thus far the identification of virulence factors for Brucella has been largely dependent on large-scale screens and testing in model systems. The genomes of the facultative intracellular pathogens Brucella melitensis and Brucella suis were sequenced recently. This has identified several more potential virulence factors for Brucella that were not found in large screens. Here, we present an overall view of Brucella virulence by compiling virulence data from the study of 184 attenuated mutants.


Great Salt Lake microbiology: a historical perspective.
Over geologic time, the water in the Bonneville basin has risen and fallen, most dramatically as freshwater Lake Bonneville lost enormous volume 15,000-13,000 years ago and became the modern day Great Salt Lake. It is likely that paleo-humans lived along the shores of this body of water as it shrunk to the present margins, and native peoples inhabited the surrounding desert and wetlands in recent times. Nineteenth century Euro-American explorers and pioneers described the geology, geography, and flora and fauna of Great Salt Lake, but their work attracted white settlers to Utah, who changed the lake immeasurably. Human intervention in the 1950s created two large sub-ecosystems, bisected by a railroad causeway. The north arm approaches ten times the salinity of sea water, while the south arm salinity is a meager four times that of the oceans. Great Salt Lake was historically referred to as sterile, leading to the nickname "America's Dead Sea." However, the salty brine is teaming with life, even in the hypersaline north arm. In fact, scientists have known that this lake contains a diversity of microscopic lifeforms for more than 100 years. This essay will explore the stories of the people who observed and researched the salty microbiology of Great Salt Lake, whose discoveries demonstrated the presence of bacteria, archaea, algae, and protozoa that thrive in this lake. These scientists documented the lake's microbiology as the lake changed, with input from human waste and the creation of impounded areas. Modern work on the microbiology of Great Salt Lake has added molecular approaches and illuminated the community structures in various regions, and fungi and viruses have now been described. The exploration of Great Salt Lake by scientists describing these tiny inhabitants of the brine illuminate the larger terminal lake with its many facets, anthropomorphic challenges, and ever-changing shorelines.


Simvastatin improves learning and memory impairment via gut-brain axis regulation in an ovariectomized/D-galactose Alzheimer's rat model.
Alzheimer's disease (AD) is the most prevalent form of dementia with multiple etiology and no effective remedy. Statins are a group of medicines that are basically used to lower cholesterol. However, several studies have recently done to assess the potential relationship between statins use and dementia but presented controversial results. In this study, using ovariectomy and D-galactose injection, a model of AD was induced in female rats, and then the protective effects of oral administration of simvastatin were investigated. shuttle box and Y-maze tests were done to assess the animals' learning and memory performance. Using GC-MC, ELISA, Immunohistochemistry and tissue staining techniques, changes in the amount of short-chain fatty acids (SCFAs), plasma and hippocampus neuroinflammatory markers and histological changes in the intestine and hippocampus were assessed in sham, disease and treatment groups. Oral administration of simvastatin improved the gut microbiome activity (increased the amount of SCFAs in fecal samples) and strengthened the tight junctions of intestinal cells. Moreover, simvastatin reduced the amount of TNF-α and IL-1β in plasma and hippocampus. Also, cell death and Amyloid plaques notably decreased in the simvastatin-treated hippocampal tissue. All these physiological changes led to better performance in behavioral tasks in the treatment group in comparison to the disease group. These findings provide evidence that simvastatin may improve gut-brain axis followed by improvement in learning and memory via an anti-inflammatory effect.


Social support and occupational stress: a causal analysis.
This study is aimed at gaining insight into the role of social support provided by coworkers and supervisors in the reduction of job-stress. It is emphasized that, despite the inclusion of social support as an important variable in theoretical models of job stress, research on this issue is plagued by a lack of conceptual clarity, disagreement on definitions, and divergent operationalizations. Furthermore, there is little strong empirical evidence for the role of social support in alleviating job stress. Moreover, because of the use of cross-sectional designs, causal interpretations are often impossible. In this study, an attempt was made to assess the causal direction of the relationships between social support, stressors and strains, by employing a longitudinal panel design and LISREL analysis. Subjects consisted of 2034 employees of 21 Dutch companies from the eastern part of the Netherlands. All filled out a questionnaire on organizational stress and social support, and underwent a medical examination. Parts of the sample participated in two follow-up measurements. The results showed that individuals from the highest occupational levels as well as those from the lowest perceived less social support than other individuals. Furthermore, the respondents consistently reported that coworkers provide more support than supervisors. Only in the group with the lower occupational level did social support have a causal effect upon most stressors, indicating that social support indeed reduces role ambiguity, role overload, role conflict and job future uncertainty. However, there was not much evidence for a causal effect of social support by the coworkers upon the stressors.(ABSTRACT TRUNCATED AT 250 WORDS)


Knowledge of obstetric danger signs and associated factors among pregnant women in Erer district, Somali region, Ethiopia.
Knowledge of danger signs of obstetric complications is first step in the appropriate and timely referral to essential obstetric care. Although women's knowledge about the obstetric danger signs is important for improving maternal and child health, little is known about the current knowledge and influencing factors in pastoral community of Ethiopia. This study, therefore, aims to fill this gap by assessing the current level of knowledge and associated factors of pregnant women living in Erer district of Somali region, Ethiopia. A community based, cross-sectional study was conducted from April 7 to 21, 2014. The study involved 666 pregnant women residing in the district. Two-stage sampling technique was used to select the study subjects. Data about women's socio-demographic information, reproductive history, knowledge of the danger signs, exposure to media and interventions were collected by interviewer administered questionnaires. A respondent who spontaneously mentioned at least two of the danger signs during each of the three periods was considered knowledgeable; otherwise not. Descriptive, bivariate, then multivariable logistic regression were done. Six hundred thirty two pregnant women were interviewed with a response rate of 94.9 %. Only 98 (15.5 %) respondents were knowledgeable about obstetric danger signs. Urban residence [AOR = 2.43; 95 % CI (1.40, 4.21)], women who had been pregnant five or more times [AOR = 6.65; 95 % CI (2.48, 17.89)] and antenatal care utilization [AOR = 5.44; 95 % CI (3.26, 9.09)] were associated with being knowledgeable about obstetric danger signs during pregnancy, childbirth and postpartum. A significant proportion of pregnant women in Erer district do not have knowledge of obstetric danger signs. The implication is that lack of recognition may lead to delay in seeking care. Area of residence, gravidity and antenatal care service utilization are independently associated with the knowledge of women on obstetric danger signs in Erer district, a pastoralist community. Thus, intervention programs aiming to improve women's knowledge about obstetric danger signs and symptoms should consider the factors independently associated.


Pseudo-tumours, a clinical concept.
Space-filling lesions in the orbit can be divided into 3 large groups: 1. Acute and subacute inflammatory processes (bacterial, fungal, parasitic, foreign body). 2. Benign and malignant tumours, true new growths. 3. Pseudo-tumours. The conditions in group 3 are also space-filling lesions, but have the characteristics of a chronic, infiltrating, inflammatory process. In 11% of 340 consecutive patients in the Orbital Centre in Amsterdam this diagnosis was made. The group is far from uniform: the dominant cell type varies from one case to another. Usually lymphocytic cells are dominant; if these are arranged in follicles the lesion is called a pseudo-lymphoma. This condition can gradually leave the province of the pseudo-tumours and begin to show the characteristics of a malignant or non-Hodgkin lymphoma. Sometimes the inflammatory character of the lymphoid infiltration is dominant, as in myositis, sclerotenonitis and infiltrative Graves' ophthalmopathy; these conditions are clearly related to immunological processes. Attempts to classify all pseudo-tumours on a pathological basis have remained rather vague. rapid development (2-6 months); pain and oedema are present, but these are not the principal symptoms; secondary features are: disorders of motility, visual loss and other symptoms. Bilaterality usually indicates the presence of a systemic disease.


PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice.
Attention system abnormalities represent a significant barrier to scholastic achievement in children with neurofibromatosis-1 (NF1). Using a novel mouse model of NF1-associated attention deficit (ADD), we demonstrate a presynaptic defect in striatal dopaminergic homeostasis and leverage this finding to apply [(11)C]-raclopride positron-emission tomography (PET) in the intact animal. While methylphenidate and l-Deprenyl correct both striatal dopamine levels on PET imaging and defective attention system function in Nf1 mutant mice, pharmacologic agents that target de-regulated cyclic AMP and RAS signaling in these mice do not. These studies establish a robust preclinical model to evaluate promising agents for NF1-associated ADD.


Unusual combination of genetic defects in a Sicilian boy: G gamma delta beta thalassemia, G gamma A gamma heterocellular HPFH, beta (0) thalassemia, and albinism.
We describe the clinical and hematological findings in a 5-year-old boy with G gamma A gamma delta beta thalassemia, a G gamma A gamma heterocellular form of HPFH, beta(0) thalassemia, and albinism. Clinically he manifested only the characteristics of beta-thalassemia trait and not the typical picture of doubly heterozygous beta thal/delta beta thal. The simultaneous presence of heterocellular HPFH improves gamma chain synthesis, thus reducing the alpha chain excess. It is also possible that gene expression can be modified by the presence of other genetic anomalies.


A stochastic model of homeostasis: The roles of noise and nuclear positioning in deciding cell fate.
We study a population-based cellular model that starts from a single stem cell that divides stochastically to give rise to either daughter stem cells or differentiated daughter cells. There are three main components in the model: nucleus position, the underlying gene-regulatory network, and stochastic segregation of transcription factors in the daughter cells. The proportion of self-renewal and differentiated cell lines as a function of the nucleus position which in turn decides the plane of cleavage is studied. Both nuclear position and noise play an important role in determining the stem cell genealogies. We have observed both long and short genealogies in model simulation, and these compare well with experimental results from neuroblast and B-cell division. Symmetric divisions are observed in apical nuclei, while asymmetric division occurs when the nucleus is toward the base. In this model, the number of clones decreases over time, although the average clone size increases.


Quantitative and Qualitative Analysis of Phenolic and Flavonoid Content in Moringa oleifera Lam and Ocimum tenuiflorum L.
Number of secondary compounds is produced by plants as natural antioxidants. Moringa oleifera Lam. and Ocimum tenuiflorum L. are known for their wide applications in food and pharmaceutical industry. To compare phenolic and flavonoid content in M. oleifera Lam and O. tenuiflorum L. by quantitative and qualitative analysis. Phenolic and flavonoid content were studied spectrophotometrically and by paper chromatography in M. oleifera Lam. and O. tenuiflorum L. Higher phenolic and flavonoid content were observed in Moringa leaf and flower. Ocimum flower showed higher phenolic content and low flavonoid in comparison to Moringa. Flavonoids such as biflavonyl, flavones, glycosylflavones, and kaempferol were identified by paper chromatography. Phytochemical analysis for flavonoid, tannins, saponins, alkaloids, reducing sugars, and anthraquinones were tested positive for Moringa and Ocimum leaf as well as flower. In the present study higher phenolic and flavonoid content, indicated the natural antioxidant nature of Moringa and Ocimum signifying their medicinal importance. Moringa oleifera Lam. and Ocimum tenuiflorum L. are widly grown in India and are known for their medicinal properties. Number of secondary metabolites like phenolics and flavonoids are known to be present in both the plants. The present study was conducted with an objective to qualitatively and quantitatively compare the phenolics and flavanoids in these two medicinally important plants.Quantitation of total phenolics and flavanoids was done by spectrophotometrically while qualitative analysis was perfomed by paper chromatography and by phytochemical tests. Our results have shown higher phenolics and flavanoid content in Moringa leaf and flower. However, higher phenolic content was absent in Ocimum flower compared to that of Moringa. Phytochemical analysis of various metabolites such as flavonoids, tanins, sapponins, alkaloids, anthraquinones revealed that both the plant extracts were rich sources of secondary metabolites and thus tested positive for the above tests. Various flavanoids and Phenolics were identified by paper chromatography based on their Rf values and significant colors. From the above study we conclude that Moringa and Ocimum are rich in natural antioxidants hence are potent source in pharmaceutical industry.


Cu-Kojic Acid Complex Anchored to Functionalized Silica-MCM-41: A Promising Regioselective and Reusable Nanocatalyst for Click Reaction.
Cu-Kojic acid (KA) complex anchored to functionalized silica-MCM-41 was synthesized via the process of postgrafting and introduced as an effective, new, reusable, and thermally resistant heterogeneous nanocatalyst for the clean synthesis of 1H-1,2,3-triazoles from Click reaction of 2-(azidomethyl)-5-benzyloxy-4-pyrone and azido Kojic acid with a variety of terminal alkynes in excellent yields. The structure of nanocatalyst was analyzed by ICP, BET, XRD, EDS, SEM, TGA, TEM, and FT-IR techniques.


A Short Term Comparison of Cartilage with Temporalis Fascia Graft Tympanoplasty in Paediatric and Adolescent Population.
To compare the anatomic and functional outcomes of the cartilage and temporalis fascia graft materials in type 1 tympanoplasty in paediatric and adolescent population. A total of 55 patients aged <18 years who required type 1 tympanoplasty were selected. 30 patients underwent cartilage palisade tympanoplasty and 25 using temporalis fascia grafts. The age, the side of the operated ear, the operative technique, pre- and post operative pure tone and impedance audiological results, and the status of the graft were noted. Graft was considered taken up if there was successful closure of tympanic membrane perforation. At the end of 6 months, the graft take rate for cartilage was 90% and for temporalis fascia it was 80% (p > 0.05). ABG closure ratio in cartilage group was 58.54 ± 23.10% and in temporalis fascia group was 56.46 ± 27.4% (p > 0.05). Pre operatively all patients had type B tympanogram in both the groups. While post operatively either type A or C curve was seen in 80% patients of cartilage and 68% patients of temporalis fascia group. Hearing outcomes and graft success rates were high in both fascia and cartilage graft groups but not significantly different.


Isolation of iodide-oxidizing bacteria from iodide-rich natural gas brines and seawaters.
Iodide-oxidizing bacteria (IOB), which oxidize iodide (I-) to molecular iodine (I2), were isolated from iodide-rich (63 microM to 1.2 mM) natural gas brine waters collected from several locations. Agar media containing iodide and starch were prepared, and brine waters were spread directly on the media. The IOB, which appeared as purple colonies, were obtained from 28 of the 44 brine waters. The population sizes of IOB in the brines were 10(2) to 10(5) colony-forming units (CFU) mL(-1). However, IOB were not detected in natural seawaters and terrestrial soils (fewer than 10 CFU mL(-1) and 10(2) CFU g wet weight of soils(-1), respectively). Interestingly, after the enrichment with 1 mM iodide, IOB were found in 6 of the 8 seawaters with population sizes of 10(3) to 10(5) CFU mL(-1). 16S rDNA sequencing and phylogenetic analyses showed that the IOB strains are divided into two groups within the alpha-subclass of the Proteobacteria. One of the groups was phylogenetically most closely related to Roseovarius tolerans with sequence similarities between 94% and 98%. The other group was most closely related to Rhodothalassium salexigens, although the sequence similarities were relatively low (89% to 91%). The iodide-oxidizing reaction by IOB was mediated by an extracellular enzyme protein that requires oxygen. Radiotracer experiments showed that IOB produce not only I2 but also volatile organic iodine, which were identified as diiodomethane (CH2I2) and chloroiodomethane (CH2ClI). These results indicate that at least two types of IOB are distributed in the environment, and that they are preferentially isolated in environments in which iodide levels are very high. It is possible that IOB oxidize iodide in the natural environment, and they could significantly contribute to the biogeochemical cycling of iodine.


Inhibition of lipid peroxidation mediated by indolizines.
Esters, ethers, carbonates and carbamates of 1-indolizinols and azaindolizinols exhibit a profound inhibition of lipid peroxidation in vitro. The antioxidants were prepared by cyclization of pyridines and diazines with diphenylcyclopropenone followed by introduction of the O-substituent.


Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model.
Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. The leak pressures observed for non-crosslinked NCEM (137.8 +/- 22.3 mmHg), crosslinked XCEM0005 (109.1 +/- 14.1 mmHg), XCEM001 (150.1 +/- 16.0 mmHg), XCEM0033 (98.8 +/- 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 +/- 10.8 mmHg) and SIS (one and four layers) (62.6 +/- 11.8 and 57.6 +/- 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 +/- 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.


Magnetically responsive microspheres for the pulsed delivery of insulin.
This paper describes a new formulation for triggered delivery of insulin which consisted of magnetic particles dispersed in alginate spheres. When magnetic field was applied to that system, the release rate of insulin was about 50 times higher than in the absence of magnetic field. The influence of oscillating magnetic field was tested, in the same experimental conditions, on polyethylenimine cross-linked alginate spheres. In that case, the pulsed delivery of insulin occurred not immediately but during the period just after applying the magnetic field. The proposed magnetically responsive alginate spheres open new perspectives for the rhythmically delivery of peptides.


Novel mutations in CYBB Gene Cause X-linked chronic Granulomatous Disease in Pakistani patients.
Chronic Granulomatous Disease (CGD) is a primary immunodeficiency that causes susceptibility to recurrent fungal and bacterial infections. The CYBB gene encodes gp91phox component of the Phagocytic Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and specifically, X-linked CGD is caused by mutations in the CYBB gene, located on the X chromosome. The aim of the study was to characterize functional and genetic mutations in X-linked CGD. Functional analysis was conducted on the whole blood of seventeen male individuals who were suspected to have X-linked chronic granulomatous disease (CGD). Flow cytometry was employed to assess the capacity of NADPH oxidase, measuring both H2O2 production and gp91phox protein expression in neutrophils. Additionally, DNA Sanger sequencing was performed for genetic analysis. The pathogenicity of novel mutations was assessed by pathogenicity prediction tools. Among the seventeen patients evaluated, five patients (P1, P2, P3, P4, and P5) displayed impaired H2O2 production by their neutrophils upon stimulation with Phorbol myristate acetate (PMA), accompanied by abnormal gp91phox expression. DNA sequencing of the CYBB gene identified specific mutations in each patient. In P1 and P2 (previously reported cases), a hemizygous missense mutation, c.925G > A/p.E309K was identified. In P3 and P4 (novel cases), hemizygous nonsense mutations, c.216T > A/p.C72X were found. Lastly, in P5 (also a novel case), a hemizygous missense mutation, c.732T > G/p.C244W was detected. These mutations reside in exons 9,3 and 7 of the CYBB gene, respectively. The current study contributes to the understanding of the clinical and genetic spectrum associated with X-linked chronic granulomatous disease (CGD). It highlights the significance of early diagnosis in CGD and emphasizes the importance of lifelong prophylaxis to prevent severe infections.


Macrophage-secreted interleukin-35 regulates cancer cell plasticity to facilitate metastatic colonization.
A favorable interplay between cancer cells and the tumor microenvironment (TME) facilitates the outgrowth of metastatic tumors. Because of the distinct initiating processes between primary and metastatic tumors, we investigate the differences in tumor-associated macrophages (TAMs) from primary and metastatic cancers. Here we show that dual expression of M1 and M2 markers is noted in TAMs from primary tumors, whereas predominant expression of M2 markers is shown in metastatic TAMs. At metastatic sites, TAMs secrete interleukin-35 (IL-35) to facilitate metastatic colonization through activation of JAK2-STAT6-GATA3 signaling to reverse epithelial-mesenchymal transition (EMT) in cancer cells. In primary tumors, inflammation-induced EMT upregulates IL12Rβ2, a subunit of the IL-35 receptor, in cancer cells to help them respond to IL-35 during metastasis. Neutralization of IL-35 or knockout of IL-35 in macrophages reduces metastatic colonization. These results indicate the distinct TMEs of primary and metastatic tumors and provide potential targets for intercepting metastasis.


Orthogonal bis(terpyridine)-Fe(II) metal complex oligomer wires on a tripodal scaffold: rapid electron transport.
The present work reports a tripodal scaffold for bis(terpyridine)-Fe(II) oligomer wires on an Au(111) surface: the tripodal scaffold realised both orthogonality of the oligomer wires, and fast interfacial electron transfer through the oligomer wires.


Receptors for immunoglobulin isotypes (FcR) on murine T cells. I. Multiple FcR expression on T lymphocytes and hybridoma T cell clones.
T cell receptors for the Fc portion of the various isotypes of mouse immunoglobulins (FcR) were examined by rosette formation, using as indicator cells erythrocytes coated with monoclonal antibodies of all known isotypes of serum immunoglobulins. Three populations of mouse T cells were studied: normal thymocytes, activated T cells (ATC), generated by educating thymocytes in lethally irradiated allogeneic hosts, and hybridoma T cells, derived from somatic hybridization of ATC with the FcR-negative thymoma BW.5147. We found that many different FcR could be distinguished by their specificity for a single isotype or for a combination of several isotypes; ATC and hybridoma T cells expressed several such receptors that, at least in cloned cells, could be demonstrated to be borne by individual cells; hybridoma T cells of independent origin bore indistinguishable receptors whereas ATC expressed markedly different FcR and upon overnight incubation at 37 degrees C, immunoglobulins were found to bind onto the cell surface, even though no corresponding constitutive FcR was detected. The same was observed with hybridoma T cells and with thymocytes. It follows that a single T cell can express several FcR. Altogether, these FcR are capable of binding all known isotypes of serum immunoglobulins. They differ from one T cell to another.


Effectiveness of cross-linked human acellular dermal matrix in primary and revision augmentation rhinoplasty.
Among the materials used for dorsal augmentation rhinoplasty (DAR), cross-linked human acellular dermal matrix (ADM) has been claimed for its low risk of infection and extrusion. The aim of this study was to compare the effectiveness of ADM in subjects undergoing primary versus revision dorsal augmentation rhinoplasties. Using a retrospective cohort study design, the investigators enrolled a cohort set of DAR patients operated by a single surgeon during a 65-month interval. The predictor variable was the treatment group (primary or revision DAR). The main outcome variables were postoperative changes with regard to the degree of augmentation (ratio of the dorsal height [DH] and radix height [RH] to the nasal length) and patients' and surgeons' satisfaction with the aesthetic and functional results. Other study variables were grouped into the following categories: demographic, surgical, and pathological. Descriptive, uni-, and bivariate statistics were computed using P ≤ 0.05 as a cutoff value. The study cohort comprised 145 subjects (75.2% with primary DAR; 39.3% females) with a mean age of 30.7 ± 9.4 years (range, 19-58). DAR was linked to the significant changes in DH and RH in both the treatment groups. Comparison of the two groups revealed that there was no significant difference in DH and RH between both the groups. Surgeons' and patients' satisfaction rates were comparable between the two surgery groups, neither of which experienced serious complications. Microscopic findings of the removed ADM showed abundant collagen tissue with newly formed vessels without signs of foreign body reaction. Despite significant differences in patient characteristics (age; number of osteotomy, tip plasty, and hump reduction surgeries), the results of this study suggest that ADM can be used in both primary and revision DAR, with minimal complications.


Stereochemical Inversion of Rim-Differentiated Pillar[5]arene Molecular Swings.
To investigate the dynamic stereochemical inversion behavior of pillar[5]arenes (P[5]s) in more detail, we synthesized a series of novel rim-differentiated P[5]s with various substituents and examined their rapid rotations by variable-temperature NMR (203-298 K). These studies revealed for the first time the barrier of "methyl-through-the-annulus" rotation (ΔG‡ = 47.4 kJ·mol-1 in acetone) and indicated that for rim-differentiated P[5]s with two types of alkyl substituents, the smaller rim typically determines the rate of rotation. However, substituents with terminal C═C or C≡C bonds give rise to lower inversion barriers, presumably as a result of attractive π-π interactions in the transition state. Finally, data on a rim-differentiated penta-methyl-penta-propargyl P[5] exhibited the complexity of the overall inversion dynamics.


Development, method validation and simultaneous quantification of eleven bioactive natural products from high-altitude medicinal plant by high-performance liquid chromatography.
Herein, a novel, rapid, reliable, simple method validation and simultaneous quantification of 11 bioactive compounds (mostly xanthones) have been described. International Conference on Harmonization guidelines were used for the analytical method validation. Good linearity, repeatability, intra- and inter-day precision, accuracy and reliability were well-illuminated in the method validation procedure. The calibration curves showed a good linear relationship (r > 0.999) within test range. Precision was evaluated by intra- and inter-day tests with relative standard deviation <2.79% and accuracy validation recovery of 74.16%-91.84%. On quantification study, the validated method described the high content of bioactive xanthone derivatives, including 1-hydroxy-3, 5-dimethoxyxanthone (7), 2-(allyloxy)-8-hydroxy-1, 6-dimethoxyxanthone (6) 1, 7, 8-trihydroxy-3-methoxyxanthone (9) and Coxanthone E (5) in Codonopsis ovata, which is advantageous given the numerous pharmacological and biological effects associated with these compounds, which mostly exhibit anti-cancerous, antioxidant, anti-inflammatory, anti-mutagenic and anti-obesity effects. The bulk abundance of these compounds can also be used for further modification to produce better lead molecules for drug discovery with low toxicity and high potency. The proposed method makes it possible to simultaneously determine all bioactive compounds in one run and can be extended to marker-based standardization of herbal formulations in medicinal and pharmaceutical industries.


Biopsychosocial problem-related distress in cancer: examining the role of sex and age.
The current study explores how sex and age relate to biopsychosocial distress by applying a large-scale analysis among individuals diagnosed with a variety of cancers. A retrospective study was conducted involving 6462 patients treated for cancer at a National Cancer Institute-designated comprehensive cancer center between 2009 and 2014. Patients were asked to complete the biopsychosocial problem-related distress touchscreen instrument prior to starting treatment as part of their routine clinical care. There was a significant interaction of age and sex on the total number of problems rated as high distress and the total number of problems that prompted a request to talk with a member of the team. Male patients between 18 and 39 reported significantly more problems as high distress than female patients in the same age group (mean = 5.34 and mean = 4.92, respectively; p = 0.005). A similar trend was found where male patients between 18-39 and 40-64 requested to talk with a member of the team significantly more often than female patients in these same age groups (mean = 3.25 and mean = 3.22 vs. mean = 2.70 and mean = 3.07, respectively; p = 0.016). The results of the current study serve to refute generalizations regarding age or gender demographics and support preferences and thus reinforce the need to offer services in the context of cancer in flexible and varied ways. Copyright © 2016 John Wiley & Sons, Ltd.


Inhibition of butylated hydroxytoluene-induced mouse lung cell division by oxygen: time-effect and dose-effect relationships.
Mice were injected i.p. with 250 or 400 mg/kg of butylated hydroxytoluene (BHT). In vivo incorporation of thymidine into pulmonary DNA was measured on days 1-7 after BHT. 2, 3 and 4 days after BHT, DNA synthesis was inhibited by a 24-h exposure to 100% oxygen, whereas on days 5, 6 and 7 after BHT, oxygen failed to depress synthesis. A similar pattern was observed when incorporation of leucine into protein was measured: 2 and 4 days after BHT, oxygen decreased leucine incorporation, but had no effect 6 days after BHT or in animals not pretreated with BHT. It is concluded that the cells proliferating early after BHT, the type II alveolar cells, are more susceptible to the cytotoxic effects of oxygen than are interstitial and capillary endothelial cells.


Promotion of acid-induced membrane fusion by basic peptides. Amino acid and phospholipid specificities.
The ability of oligo- and polymers of the basic amino acids L-lysine, L-arginine, L-histidine and L-ornithine to induce lipid intermixing and membrane fusion among vesicles containing various anionic phospholipids has been investigated. Among vesicle consisting of either phosphatidylinositol or mixtures of phosphatidic acid and phosphatidylethanolamine rapid and extensive lipid intermixing, but not complete fusion, was induced at neutral pH by poly-L-ornithine or L-lysine peptides of five or more residues. When phosphatidylcholine was included in the vesicles, the lipid intermixing was severely inhibited. Such lipid intermixing was also much less pronounced among phosphatidylserine vesicles. Poly-L-arginine provoked considerable leakage from the various anionic vesicles and caused significantly less lipid intermixing than L-lysine peptides at neutral pH. When the addition of basic amino acid polymer was followed by acidification to pH 5-6, vesicle fusion was induced. Fusion was more pronounced among vesicles containing phosphatidylserine or phosphatidic acid than among those containing phosphatidylinositol, and occurred also with vesicles whose composition resembles that of cellular membranes (i.e., phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine, 50:30:20, by mol). Liposomes with this composition are resistant to fusion by Ca2+ or by acidification after lectin-mediated contact. The tight interaction among vesicles at neutral pH, resulting in lipid intermixing, does not seem to be necessary for the fusion occurring after acidification, but the basic peptides nevertheless appear to play a more active role in the fusion process than simply bringing the vesicles in contact. However, protonation of the polymer side chains and transformation of the polymer into a polycation does not explain the need for acidification, since the pH-dependence was quite similar for poly(L-histidine)- and poly(L-lysine)-mediated fusion.


Endoscopic and histologic analysis of gastric mucosa-associated lymphoid tissue in children with Helicobacter pylori infection.
Nodular gastritis (NG) associated with Helicobacter pylori infection can occur commonly in childhood and is regarded to be benign without clinical significance. This study includes endoscopic and histologic analysis of gastric mucosa-associated lymphoid tissue (MALT) to clarify the significance of NG on endoscopy in H pylori-infected children. Of the 758 children who underwent endoscopy, 80 were identified as having H pylori infection. These patients were divided into 3 groups based on endoscopic severity of gastric nodularity. Histopathologic grading of MALT and immunohistochemistry of CD3, CD20, cytokeratin, and Ki-67 were evaluated. On endoscopy, severe NG was observed in the antrum of 38 of the 80 subjects, mild NG in 27, and an absence of NG in 15. Density of H pylori and lymphocyte infiltration differed among the 3 groups (P=0.022 and P=0.025, respectively). Histological grading for gastric lymphoid infiltrates was compatible with grade 1 in 47 (58.8%), grade 2 in 21 (26.3%), grade 3 in 7 (8.8%), and grade 4-5 in 4 (5.1%) in the antrum. Degree of NG, density of H pylori, neutrophil activity, and gastritis score in the antrum varied with MALT grades (P=0.003, P=0.042, P=0.028, and P=0.006, respectively). Our study suggests NG may present as a significant gastric manifestation of childhood H pylori infection that indicates gastric MALT. Thorough histologic investigation may be useful in the evaluation of gastric MALT in children infected with H pylori that manifests as severe NG in the antrum.


Decisions to be made when initiating enteral nutrition.
Enteral nutrition support is preferred to parenteral or no nutritional support, but many patients who could benefit receive inadequate enteral feeding. Many decisions must be made before initiating enteral nutrition support; including if and when enteral nutrition should be started, which formula should be used, and how enteral nutrition support should be monitored. The gastroenterologist should be able to understand and evaluate these decisions in all patients potentially requiring nutritional support.


Cold stress increases reactive oxygen species formation via TRPA1 activation in A549 cells.
Reactive oxygen species (ROS) are responsible for lung damage during inhalation of cold air. However, the mechanism of the ROS production induced by cold stress in the lung is still unclear. In this work, we measured the changes of ROS and the cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 to 5 °C) exposure of A549 cell resulted in an increase of ROS and [Ca(2+)]c, which was completely attenuated by removing Ca(2+) from medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) agonist (allyl isothiocyanate, AITC) increased the production of ROS and the level of [Ca(2+)]c in A549 cell. Moreover, HC-030031, a TRPA1 selective antagonist, significantly inhibited the enhanced ROS and [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data demonstrated that TRPA1 activation played an important role in the enhanced production of ROS induced by cold stress in A549 cell.


Nonspecific inhibitor of contact sensitivity made by T-acceptor cells: triggering of T cells armed with antigen-specific T-suppressor factor (TsF) requires both occupancy of the major histocompatibility complex recognition site by soluble I-J product and cross-linking of the antigen recognition sites of the TsF.
The phenomenon of associative recognition, i.e., the recognition of antigen together with major histocompatibility complex products (MHC) was studied in a model system. T-acceptor cells armed with antigen-specific T-suppressor factor (TsF) released a nonspecific inhibitor of the transfer of contact sensitivity when exposed to antigen together with MHC. The MHC product occurred in a KCl extract of cells and behaved genetically and serologically as I-J. Cells armed with anti-picryl or anti-"oxazolone" TsF could be triggered by the corresponding "bis-picryl-L-lysine" and "bis-oxazolone-L-lysine" together with MHC. This suggested that cross-linking of antigen recognition sites on separate molecules of TsF might be required. To investigate this possibility the bifunctional "mixed" hapten "N alpha-picryl-N epsilon-oxazolone-L-lysine," which is univalent with respect to the picryl and oxazolone haptenic groups, was synthesized. This triggered cells armed with a mixture of anti-picryl and anti-oxazolone TsF but not cells armed with either TsF alone. It was concluded that both occupancy of the I-J recognition site and the cross-linking of separate molecules of TsF was required for triggering. Moreover the hapten and the KCl extract could be given sequentially and in either order. This finding suggested that the triggering of the release of nonspecific inhibitor was due to the separate recognition of I-J and antigen and not to new antigenic determinants produced by their interaction.


Temporal correlation of succinylcholine-induced fasciculations to loss of twitch response at different stimulating frequencies.
The present study was undertaken to determine the time courses of succinylcholine-induced fasciculations and adductor pollicis single-twitch responses at two stimulating frequencies. A prospective, randomized study. The main operating room of a university teaching hospital. Forty-four patients undergoing general anesthesia and requiring tracheal intubation. In 22 patients, anesthesia was induced with thiopental sodium, fentanyl, and midazolam and maintained with 70% nitrous oxide in oxygen prior to the administration of succinylcholine 1 mg/kg. In another 22 patients, end-tidal isoflurane 0.75% to 1% was included in the induction regimen. Patients in each group were randomly assigned to receive ulnar nerve stimulation at either 0.1 Hz or 1.0 Hz. The times at which fasciculations were first noticed and no longer visible and the times to 25%, 50%, 75%, 90%, and 100% twitch depression were recorded. These times were compared for the two rates of neurostimulation. With single-twitch nerve stimulation at 1.0 Hz, 100% twitch depression occurred 6 +/- 16 seconds following the end of fasciculations, while at a stimulating frequency of 0.1 Hz, it occurred 52 +/- 32 seconds later (p less than 0.05). At the end of fasciculations, single-twitch depression of 50% or more was noted in only 19% of patients in the 0.1 Hz groups and in all patients in the 1.0 Hz groups (p less than 0.05). In the 0.1 Hz groups, 50% twitch depression occurred 19 +/- 27 seconds after the end of fasciculations, with more than three-quarters of the patients having achieved 50% twitch depression 30 seconds following the disappearance of fasciculations. The addition of isoflurane did not significantly alter any of these times. The data reveal that cessation of fasciculations may be an inaccurate clinical sign of the readiness for intubation and confirm that standardized methods of neurostimulation are necessary in the pharmacodynamic evaluation of neuromuscular blocking drugs. In settings where profound neuromuscular relaxation is not required, waiting at least 30 seconds beyond the disappearance of fasciculations should provide good intubating conditions.


AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity.
Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at S511, which triggers IRF3 recruitment and the assembly of MAVS or STING signalosomes. Consistently, ablation or inhibition of AMPK, knockin of TBK1-S511A, or increased glucose levels compromised nucleic acid sensing, while boosting AMPK-TBK1 cascade by AICAR or TBK1-S511E knockin improves antiviral immunity substantially in various animal models. Thus, we identify TBK1 as an AMPK substrate, reveal the molecular mechanism coupling a dual sensing of glucose and nuclei acids, and report its physiological necessity in antiviral defense.


Development of severe alcohol related liver disease over four decades in Iceland: impact of increased access and use of alcohol.
Limited data exist on the association between per capita alcohol consumption and incidence of alcohol related liver disease (ARLD). The aims were to analyse this relationship and assess prevalence of ARLD in Iceland and among patients treated for alcohol use disorder (AUD) and its impact on outcomes. A retrospective study on all patients diagnosed with severe ARLD: alcohol related cirrhosis (ARC) and alcohol related hepatitis (ARH) in Iceland 1984-2020. Medical records were scrutinized for clinical features, severity of ARLD, proportion undergoing treatment for AUD, data on abstinence and long-term outcomes. A total of 314 patients, males 76%, median age 56 years, fulfilled the predetermined criteria for ARLD. Median MELD was 17, 73% with Child-Pugh B/C and 70/314 (22%) who had ARH. Incidence of ARLD increased from 0.77 cases per 100 000 inhabitants annually 1984-2000 to 6.1 per 100 000 in 2016-2020. Per capita alcohol consumption increased from 4.3 Liters to 7.5 L in in the same time periods. Overall 220/314 (70%) with ARLD had undergone treatment for AUD. Of all individuals who had AUD treatment during the study period (n = 21.845), 1% were diagnosed with ARLD. Patients who underwent treatment for AUD after the ARLD diagnosis had better prognosis than those who had treatment prior to ARLD diagnosis (hazard ratio 2.5 [95% CI 1.3-5.0]). The incidence of ARLD increased 8-fold during the study period coinciding with 74% increase in per capita alcohol consumption. Patients with prior diagnosis of AUD had worse prognosis that needs special attention.


Combined atomic force microscopy and spectroscopic ellipsometry applied to the analysis of lipid-protein thin films.
Pulmonary surfactant is a complex mixture of phospholipids and proteins and forms a thin film at the lung alveolar interface separating air from liquid environment. The film reduces the work of breathing during repeatable compressions of the alveoli which form a characteristic multilayer upon compression. In this work, we investigated the structure of bovine lipid extract surfactant (BLES). We analysed the BLES films by atomic force microscopy (AFM) and spectroscopic ellipsometry (SE) in order to provide combined characterization of both morphology and thickness of surfactant films. We show how the spectroscopic ellipsometry can be used to supplement the data obtained by AFM. We demonstrate that indium tin oxide (ITO) substrate used for spectroscopic ellipsometry is preferable over glass substrate to enhance the optical contrast. An optical model was proposed to account for non-uniform film morphology. We obtained good correlations between the multilayer surface coverage, determined by both AFM and SE. SE measures the thickness of the first uniform monolayer as 2.6 nm that cannot be achieved by AFM imaging alone.


Intestinal metaplasia of the bladder in 89 patients: a study with emphasis on long-term outcome.
Intestinal metaplasia of the bladder is an uncommon glandular proliferation. We examined a large series of intestinal metaplasia for the clinicopathological features and discuss the significance of this lesion. All cases of intestinal metaplasia diagnosed in our institution between 1990 and 2014 were retrospectively reviewed. Patients with a history of urothelial carcinoma or concurrent adenocarcinoma were excluded. Patient characteristics, pathological features, and follow-up outcomes were obtained. We identified 89 patients with intestinal metaplasia during this period. Sixty seven were men and 22 were women. Mean age at diagnosis was 57 years (range 23-81). Common presenting complaints included haematuria (73 cases), mucosuria (13 cases), and irritative voiding symptoms (seven cases). The majority of intestinal metaplasias located on or near the trigone (67 cases). Eighty-two patients underwent transurethral resection of their lesions. Partial cystectomy was performed in the remaining seven patients. The mean follow-up of 78 patients was 105 months (range 6-255). One case of bladder adenocarcinoma was indentified 6 months later. The initial histologic findings had revealed intestinal metaplasia with severe dysplasia. Four patients presented recurrence during the follow-up, and this occurred 9, 13, 17 and 24 months after the surgery. Although intestinal metaplasia can be treated effectively by transurethral resection in most cases, its potential malignancy need to be taken into consideration after the evidence of recurrences and its association with bladder adenocarcinoma. Therefore, it is necessary to perform close surveillance following the surgery, particularly in patients with dysplastic changes.


Conversation effects on neural mechanisms underlying reaction time to visual events while viewing a driving scene: fMRI analysis and asynchrony model.
This neuroimaging study investigated the neural mechanisms of the effect of conversation on visual event detection during a driving-like scenario. The static load paradigm, established as predictive of visual reaction time in on-road driving, measured reaction times to visual events while subjects watched a real-world driving video. Behavioral testing with twenty-eight healthy volunteers determined the reaction time effects from overt and covert conversation tasks in this paradigm. Overt and covert conversation gave rise to longer visual event reaction times in the surrogate driving paradigm compared to just driving with no conversation, with negligible effect on miss rates. The covert conversation task was then undertaken by ten right-handed healthy adults in a 4-Tesla fMRI magnet. We identified a frontal-parietal network that maintained event detection performance during the conversation task while watching the driving video. Increased brain activations for conversation vs. no conversation during such simulated driving was found not only in language regions (Broca's and Wernicke's areas), but also specific regions in bilateral inferior frontal gyrus, bilateral anterior insula and orbitofrontal cortex, bilateral lateral prefrontal cortex (right middle frontal gyrus and left frontal eye field), supplementary motor cortex, anterior and posterior cingulate gyrus, right superior parietal lobe, right intraparietal sulcus, right precuneus, and right cuneus. We propose an Asynchrony Model in which the frontal regions have a top-down influence on the synchrony of neural processes within the superior parietal lobe and extrastriate visual cortex that in turn modulate the reaction time to visual events during conversation while driving.


Diffuse excessive high signal intensity in the preterm brain on advanced MRI represents widespread neuropathology.
Preterm brains commonly exhibit elevated signal intensity in the white matter on T2-weighted MRI at term-equivalent age. This signal, known as diffuse excessive high signal intensity (DEHSI) or diffuse white matter abnormality (DWMA) when quantitatively assessed, is associated with abnormal microstructure on diffusion tensor imaging. However, postmortem data are largely lacking and difficult to obtain, and the pathological significance of DEHSI remains in question. In a cohort of 202 infants born preterm at ≤32 weeks gestational age, we leveraged two newer diffusion MRI models - Constrained Spherical Deconvolution (CSD) and neurite orientation dispersion and density index (NODDI) - to better characterize the macro and microstructural properties of DWMA and inform the ongoing debate around the clinical significance of DWMA. With increasing DWMA volume, fiber density broadly decreased throughout the white matter and fiber cross-section decreased in the major sensorimotor tracts. Neurite orientation dispersion decreased in the centrum semiovale, corona radiata, and temporal lobe. These findings provide insight into DWMA's biological underpinnings and demonstrate that it is a serious pathology.


Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome.
The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic, and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with a thalamocortical function with widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data-driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data were collected from participants affected by FXS (n = 65) and matched controls (n = 70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) redistribution of lower-frequency boundaries indicating a "slower" dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS and, thus, a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in animal models.


Influence of the Hal locus and standardized stress on antibody response and in vitro reactivity of peripheral blood lymphocytes in pigs.
The antibody response to two Escherichia coli antigens (O149 and K88) and the in vitro reactivity of peripheral blood lymphocytes (PBLs) to pokeweed mitogen was studied in growing pigs after exposure to varying degrees of stress. Three experimental groups were used; transportation by lorry, transportation by lorry after a previous injection of a tranquillizing drug (amperozide), no transportation but an amperozide injection. Another group was used as a control group. This group was not transported and received no amperozide injection. The animals were the offspring of boars and sows heterozygous (Nn) for the Hal gene, and all 3 Hal genotypes (NN, Nn, nn) were identified and could thus be compared within litters. Immediately after the experimental treatment, the highest PBL reactivity was found for the amperozide-treated animals and for the non-transported animals, with no differences in reactivity between Hal genotypes. Two weeks later, the treatments caused different effects on pigs of the 3 Hal genotypes, both with regard to the PBL reactivity and the IgG response to O149. The NN pigs had a higher PBL reactivity than the nn pigs for all treatments except the 'drug + transport' class where the reverse rank order was found. The NN pigs also had a higher IgG response to O149 than the nn pigs in the 'drug + no transport' class. The amperozide treatment was followed by a higher PBL reactivity in non-transported NN pigs and in transported nn pigs. The amperozide-treated non-transported NN pigs also had a higher IgG response to O149. The highest PBL reactivity and IgG response to O149 were found mainly in pigs with the lowest cortisol levels. Pronounced differences between litters were found for both the antibody response and the PBL reactivity.


Graphene/graphite paste electrode incorporated with molecularly imprinted polymer nanoparticles as a novel sensor for differential pulse voltammetry determination of fluoxetine.
Molecularly imprinted polymer (MIP) nanoparticles including highly selective recognition sites for fluoxetine were synthesized, utilizing precipitation polymerization. Methacrylic acid and vinyl benzene were used as functional monomers. Ethylene glycol dimethacrylate was used as cross-linker agent. The obtained polymeric nanoparticles were incorporated with carbon paste electrode (CPE) in order to construct a fluoxetine selective sensor. The response of the MIP-CP electrode to fluoxetine was remarkably higher than the electrode, modified with the non-imprinted polymer, indicating the excellent efficiency of the MIP sites for target molecule recognition. It was found that the addition of a little amount of graphene, synthesized via modified hummer's method, to the MIP-CP resulted in considerable enhancement in the sensitivity of the electrode to fluoxetine. Also, the style of electrode components mixing, before carbon paste preparation, was demonstrated to be influential factor in the electrode response. Some parameters, affecting sensor response, were optimized and then a calibration curve was plotted. A dynamic linear range of 6×10(-9)-1.0×10(-7)molL(-1) was obtained. The detection limit of the sensor was calculated equal to 2.8×10(-9)molL(-1) (3Sb/m). This sensor was used successfully for fluoxetine determination in the spiked plasma samples as well as fluoxetine capsules.


The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia.
The Raf/MEK/ERK (MAPK) signal transduction cascade is a vital mediator of a number of cellular fates including growth, proliferation and survival, among others. The focus of this review centers on the MAPK signal transduction pathway, its mechanisms of activation, downstream mediators of signaling, and the transcription factors that ultimately alter gene expression. Furthermore, negative regulators of this cascade, including phosphatases, are discussed with an emphasis placed upon chemotherapeutic intervention at various points along the pathway. In addition, mounting evidence suggests that the PI3K/Akt pathway may play a role in the effects elicited via MAPK signaling; as such, potential interactions and their possible cellular ramifications are discussed.


Inactivation by u.v.-irradiation of interfering herpes simplex virus particles: interference requires a functional genome.
The sensitivity of interfering herpes simplex virus (HSV) particles to u.v.-irradiation was studied in a virus stock of HSV-1 strain ANG that contained an excess of interfering over infectious particles. Following u.v.-irradiation, samples of this virus stock were assayed for their plaque-forming capacity and their capacity to interfere with the replication of unirradiated standard virus. Depending on the assay conditions, interfering particles appeared to be less, equally, or more sensitive to u.v. light than infectious particles. It is concluded that interference is a gene function of interfering particles rather than being exerted directly by structural constituents of these particles.


Histamine release into tracheal lumen and bronchial reactivity. Effect of local allergen administration on histamine release and bronchial reactivity.
The influence of tracheal lavage with an allergen on the airway response to bronchial challenge with histamine, acetylcholine, and ascaris extract was investigated in 36 dogs. High histamine concentrations were measured in the tracheal solution after lavage with allergen. This amine, released on the mucosal surface, was observed in only very small concentrations in the circulation. Airway response to acetylcholine inhalation was significantly increased after tracheal lavage with allergen. This hyperreactivity of the lower airways induced by tracheal lavage with an allergen suggests that a reflex mechanism is involved. After histamine inhalation a significantly larger antigen-induced histamine release to tracheal lumen was observed. No influence on airway response was found after tracheal lavage with H2O.


The effect of substance P on nerve action potential propagation and cholinergic transmission in the myenteric plexus of the guinea-pig ileum.
The effect of substance P on nerve terminals in myenteric plexus of the guinea-pig ileum was investigated. Neurogenic twitches of the myenteric plexus longitudinal muscle strip were recorded. Twitches of the strip portion where excitation involved the most distal parts of cholinergic nerve terminals were more increased by local application of substance P (0.1 and 0.4 nmol/l) than twitches of the portion where excitation involved both distal and proximal parts of nerve terminals. Substance P addition to a portion of the strip conducting nerve action potentials to invade the neighbouring strip portion also augmented twitches of the latter portion so that the interference with the propagation process was considered. The effect of substance P was poorly antagonized by the addition of a substance P antagonist, (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-substance P. Compound nerve action potentials were evoked in strands of fibres of the myenteric plexus by low-frequency train stimulation (1 Hz). The addition of substance P prevented a decrease of the amplitude of responses observed under control conditions. Using high-frequency train stimulation (30 Hz) the amplitude of responses to impulses 2-7 was augmented over that to the first impulse; substance P further increased such facilitation regularly. It seems that substance P might promote nerve action potential invasion of the distal parts of nerve terminals.


Gamma Radiation-Attenuated Toxoplasma gondii Provokes Apoptosis in Ehrlich Ascites Carcinoma-Bearing Mice Generating Long-Lasting Immunity.
Pathological angiogenesis and apoptosis evasions are common hallmarks of cancer. A different approach to the antitumor effect of parasitic diseases caused by certain protozoans and helminthes had been adopted in recent years as they can affect many cancer characteristics. The present work is an attempt to assess the effect of gamma radiation-attenuated Toxoplasma gondii ME49 as an antiapoptotic and angiogenic regulator modifier on tumor growth aimed at improving cancer protective protocols. Attenuated Toxoplasma gondii ME49 was administered orally to mice 2 weeks before inoculation with Ehrlich ascites carcinoma to allow stimulation of the immune response. Hepatic histopathology and immune responses were determined for each group. Marked suppression of the tumor proliferation with induction of long-lasting immunity by stimulating interferon γ and downregulating transforming growth factor β. The level of tumor promoting inflammatory markers (STAT-3 and tumor necrosis factor α), the angiogenic factors (vascular endothelial growth factor A, integrin, and matrix metallopeptidase 2 and matrix metallopeptidase 9), as well as nitric oxide concentration were significantly decreased. This was collimated with an improvement in apoptotic regulators (cytochrome-c, Bax, Bak, and caspase 3) in liver tissues of vaccinated mice group compared to Ehrlich ascites carcinoma-bearing one. Moreover, the histopathological investigations confirmed this improvement. Hence, there is an evidence of potency of radiation attenuated Toxoplasma vaccine in immune activation and targeting tumor cell that can be used as a prophylactic or an adjuvant in combination with chemotherapeutic drugs.


Activation of hepatocyte growth factor-met autocrine loop enhances tumorigenicity in a human lung adenocarcinoma cell line.
Hepatocyte growth factor (HGF) is a multifunctional cytokine with effects on the proliferation, motility, and differentiation of cells that express its receptor Met. The co-expression of HGF and Met is common among nonsmall-cell lung cancers, especially adenocarcinoma. However, the biologic consequences of this putative HGF-Met autocrine signaling remain speculative. We have used retroviral gene transduction technique to express high levels of HGF in the NCI-H358 lung adenocarcinoma cells that have functionally active cell surface Met receptor. The activation of autocrine HGF-Met signaling was confirmed by the induction of spontaneous cell scattering activity. Compared to the parent and control cells transduced with the retroviral vector alone, HGF overexpressing H358 cells show enhanced capacity to colonize soft agar medium and to form xenograft tumors when implanted in the subcutaneous tissue of immune-deficient mice. These effects were not accompanied by changes in their growth rate in monolayer culture condition, or in the expression of vascular endothelial growth factor. The tumors formed by HGF overexpressing cells also showed more prominent glandular cell arrangement and functional activity. This report provides the direct in vivo evidence that autocrine HGF-Met signaling plays significant roles in the growth and differentiation of human lung adenocarcinoma cells.


The correlation between carotid-femoral pulse wave velocity and composition of the aortic media in CAD patients with or without hypertension.
To investigate the influence of hypertension on large artery elasticity and the microstructure of the ascending aortic media in patients with coronary artery disease (CAD), and the association between arterial compliance and composition of the ascending aorta. 60 patients with CAD who underwent coronary artery bypass graft surgery were divided into two groups: 30 patients in a hypertension group and 30 patients in a non-hypertension group. Carotid-femoral pulse wave velocity (cfPWV) was measured by an automatic device (Complior, Artech, France). The severity of coronary atherosclerosis was assessed after selective coronary angiography using the Gensini score system. A quantitative study was conducted on ascending aorta specimens by histological and computer image analysis. cfPWV of the hypertension group was higher than that of the non-hypertension group. The relative content of collagen in the ascending aortic media of the hypertension group was higher than that of the non-hypertension group, while the relative content of elastin in the ascending aortic media of the hypertension group was lower than that of the non-hypertension group. cfPWV showed a positive correlation with relative contents of collagen in the ascending aorta and a negative correlation with relative contents of elastin in the ascending aorta in the two groups. Hypertension may raise the contents of collagen and decrease the contents of elastin in the ascending aortic media of patients with CAD, which in turn may decrease the patients' large artery compliance. cfPWV may reflect the quantitative changes of collagen and elastin in the ascending aortic media in CAD patients independently of hypertension.


Syncope caused by cough-induced complete atrioventricular block.
Cough syncope is a well-recognized syndrome in which loss of consciousness follows a bout of prolonged coughing. The pathophysiology of this syndrome has been attributed to lowered cerebral perfusion pressure consequent on an increased intrathoracic pressure, which lowers cardiac output (by a Valsalva mechanism) and impairs cerebral venous return. We report a case of cough-induced syncope in which ECG monitoring showed that coughing produced paroxysmal atrioventricular block with ventricular asystole. Such a case has not previously been documented.


Size-fractionated particle-bound heavy metals and perfluoroalkyl substances in dust from different indoor air.
The indoor air quality issue and its potential health problems are attracting increasingly attentions. In this study, micro-orifice uniform deposit impactor (MOUDI) was used to sample suspended particles from four typical indoor environments, including residence, office, cyber classroom, and chemical analysis room. Size-dependent concentrations of perfluoroalkyl substances (PFASs) and heavy metals in suspended particles were analyzed. Then, the International Commission on Radiological Protection deposition model was employed to estimate deposition efficiencies and fluxes of size-fractioned PFASs and heavy metals in the human respiratory tract. Most of the contaminants deposited in head airways, where coarse particles (aerodynamic diameter or Dp > 1.8 μm) contributed the most. By contrast, in the alveolar region fine particles (Dp < 1.8 μm) were dominant. The chronic daily intake through inhalation of PFASs and heavy metals via airborne particles were 10.3-37.5 pg kg-1days-1 and 3.1-25.9 mg kg-1days-1, respectively. The estimated total hazardous quotient of PFASs and heavy metals were 4.4 × 10-5-1.7 × 10-3 and 9.9 × 10-3-1.05 × 10-1, which is far lower than the acceptable threshold of 1. However, the incremental lifetime cancer risk induced by As, Cd, Co, Cr, and Ni were estimated to be 1.11 × 10-5-1.41 × 10-4 in total, which exceeded the acceptable threshold of 10-6. These findings implicate that there were health risks, especially cancer risks caused by heavy metals associated with airborne particles in urban indoor environments.


Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules.
Cytoplasmic dynein is a dimeric AAA(+) motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo-electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA(+) rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein's directionality and unusual stepping behaviour.


Behavioral cross-sensitization between cocaine and enkephalin in the A10 dopamine region.
The motor stimulant effect produced by cocaine and the injection of opioids onto A10 dopamine neurons is thought to be mediated by an increase in dopaminergic transmission in mesolimbic dopamine terminal fields such as the nucleus accumbens. Following daily administration, the behavioral stimulant effect of both cocaine and intra-A10 injection of opioids is augmented. The data in this report demonstrate that rats receiving daily injection of enkephalin analogue into the A10 have an enhanced motor stimulant response to intraperitoneal cocaine, but not to saline. Conversely, rats receiving daily injection of intraperitoneal cocaine have an enhanced motor stimulant response to intra-A10 injection of enkephalin analogue.


Mechanistically based mapping of human cardiac fibrillation.
The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper 'On dynamic equilibrium in the heart', Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms - sources in preferred cardiac regions or spatially diffuse self-sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non-uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non-coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation.


Removal and factors influencing removal of sulfonamides and trimethoprim from domestic sewage in constructed wetlands.
Twelve pilot-scale constructed wetlands with different configurations were set up in the field to evaluate the removal and factors that influence removal of sulfonamides (sulfadiazine, sulfapyridine, sulfacetamide, sulfamethazine and sulfamethoxazole) and trimethoprim from domestic sewage. The treatments included four flow types, three substrates, two plants and three hydraulic loading rates across two seasons (summer and winter). Most target antibiotics were efficiently removed by specific constructed wetlands; in particular, all types of constructed wetlands performed well for the degradation of sulfapyridine. Flow types were the most important influencing factor in this study, and the best removal of sulfonamides was achieved in vertical subsurface-flow constructed wetlands; however, the opposite phenomenon was found with trimethoprim. Significant relationships were observed between antibiotic degradation and higher temperature and redox potential, which indicated that microbiological pathways were the most probable degradation route for sulfonamides and trimethoprim in constructed wetlands.


MicroRNA-10a Influences Osteoblast Differentiation and Angiogenesis by Regulating β-Catenin Expression.
Elucidation of the molecular mechanisms governing osteoblast differentiation and angiogenesis are of great importance for improving the treatment of bone-related diseases. In this study, we examined the role of microRNA (miR)-10a in the differentiation of MC3T3-E1 cells and pro angiogenic activity of mouse umbilical vein endothelial cells (MUVECs). The murine pre-osteoblast cell line MC3T3-E1 and MUVECs were used in the experiment. After transfected with miR-10a mimics or inhibitors, with or without LiCl pretreatment, the miR-10a, ALP, Runx2, Osx, OC and Dlx5 expression were assessed by RT-PCR. MC3T3-E1 cells were cultured with BMP2 to differentiate into bone cells, osteogenic differentiation of MC3T3-E1 cells were detected by ALP and ARS staining. Cell viability were analyzed by MTT and the protein expression of β-catenin, LEF1, cyclinD1, MMP2, and VEGF were detected by Western blotting; VEGF and VE-cadherin release were assessed by ELISA, and the migration of MUVECs, as well as tube formation were also detected. MiR-10a expression was obviously down-regulated during osteogenic differentiation. Overexpression of miR-10a inhibited osteogenic differentiation of MC3T3-E1 cells, effectively decreasing MUVECs proliferation, migration, VEGF expression, VE-cadherin concentrations, and tube formation in vitro, whereas miR-10a silence enhanced those processes. Further mechanism assays demonstrated that overexpression of miR-10a reduced the β-catenin at both protein and transcription level, while pretreatment with Wnt signaling activator Licl partially attenuated the suppression effects of miR-10a overexpression on osteoblast differentiation and angiogenesis. Our findings imply that miR-10a plays a suppressive role in osteoblast differentiation of MC3T3-E1 cells and pro angiogenic activity of MUVECs by regulating the β-catenin expression, representing a novel and potential therapeutic target for the treatment of bone regeneration-related diseases.


Analysis of the structural diversity of monoclonal antibodies to cyclosporine.
The immunosuppressive cyclic undecapeptide cyclosporine (Cs) represents a useful model for studying the molecular basis of antibody-antigen interactions. The three-dimensional structure of the Cs molecule is known and a large panel of monoclonal antibodies (mAbs) to Cs has been well characterized by cross-reactivity studies with numerous Cs analogs. In the present study, the sequences of the variable regions of seven mAbs to Cs were determined and a striking relationship was found between the expressed variable region genes and the Cs recognition pattern. An analysis of the length and hydrophobic content of the hypervariable regions and sequence similarities suggested that the heavy chain plays a major role in Cs recognition. Different fine specificities were observed for mAbs exhibiting identical light chains, while two antibodies differed by only a single amino acid located in the heavy chain. The presence of a duplication of 12 nucleotides within the heavy chain third hypervariable region of two antibodies suggests the existence of an additional mechanism for creating antibody diversity.


Occupation-related burns: five-year experience of an urban burn center.
Mortality from burns in the United States has not improved appreciably since 1955 among men, and the rate of decline among women appears to be slowing. Although one-quarter of all serious burns result from occupational accidents, few systematic epidemiologic studies of occupational burns have been conducted. We reviewed 232 cases of occupational burns among the 1,076 civilians seen as outpatients or admitted to the Regional Burn Treatment Center of the University of California Medical Center in San Diego from 1977 to 1982. Scalds were the most common type of burn overall and in women, but flame-related burns resulted in the highest average percent body surface area burned and were more common in men; tar-related, flame-related, chemical, and electrical burns affected men almost exclusively. Electrical burns were disproportionately severe, as measured by time lost from work, fatalities, and permanent disability, in relation to their frequency and amount of body surface area involved. Contact burns were more frequent in younger persons. Hispanics were overrepresented compared with their representation in the general population. Occupational associations included scalds due to hot grease among restaurant workers, tar burns among roofing workers, electrical burns among farm workers, and injuries reflecting hazards to firefighters and electricians. The number of days off work after hospitalization correlated closely with the number of days hospitalized, which in turn correlated significantly with percentage of body surface area burned.(ABSTRACT TRUNCATED AT 250 WORDS)


Stereotactic arrhythmia radioablation: A novel therapy for cardiac arrhythmia.
Cardiac arrhythmia is a global health problem, and catheter ablation has been one of its main treatments for decades. However, catheter ablation is an invasive method that cannot reach the deep myocardium, and it carries a considerable risk of side effects and recurrence. Therefore, it is necessary to explore a novel approach. Stereotactic body radiotherapy, which has been widely used in the field of radiation oncology, has recently expanded in the treatment of cardiac arrhythmia; when used in this context, it is known as stereotactic arrhythmia radioablation (STAR). As a noninvasive, effective, and well-tolerated treatment, STAR may be a suitable alternative method for patients with cardiac arrhythmia who are resistant or intolerant to catheter ablation. The main particles used to deliver energy in STAR are photons, protons, and carbon ions. Most studies have shown the short-term effectiveness of STAR, but problems such as a high long-term recurrence rate with a cumulative ventricular tachycardia-free survival rate from the published literature of 38.6% and related complications have also emerged. Therefore, in this article, we review the application of stereotactic body radiotherapy in cardiac arrhythmia, analyze its potential problems, and explore methods for improvement.


Loss of control over eating is associated with eating disorder psychopathology in a community sample of Latinas.
This study examined the association between loss of control and eating disorder psychopathology in a community sample of women of Hispanic origin. Seventy-seven monolingual Spanish-speaking Latinas recruited from the community were administered the Spanish language version of the Eating Disorders Examination (S-EDE). Latinas who reported regular (at least once weekly) loss of control-through objective bulimic episodes (OBEs) and/or subjective bulimic episodes (SBEs)-were compared with Latinas who did not report regular loss of control. Latinas who reported LOC did not differ significantly from Latinas who denied LOC in age, current body mass index, or highest adult weight. Latinas who reported LOC had significantly more frequent weight cycling and significantly higher scores on all S-EDE subscales. The findings suggest that regular loss of control over eating-regardless of the amount of food consumed-may be a marker for the presence of eating disorder psychopathology.


In vitro metabolism of cyclosporin A with rabbit renal or hepatic microsomes: analysis by HPLC-FPIA and HPLC-MS.
Cyclosporin A (CsA) is in vivo mainly metabolized by hepatic cytochrome P450 IIIA to more than 21 metabolites, the major ones known as: M1, M17 and M21. The aim of this work is to explore the in vitro metabolism of CsA after incubation, in the presence of NADPH, with renal or hepatic microsomes obtained from rabbits pretreated with rifampycin (enzyme inducer) or erythromycin (enzyme inhibitor). The presumed metabolites were separated by semi-preparative high-performance liquid chromatography (HPLC) and identified in each collected fraction by fluorescence polarization immunoassay (FPIA) (HPLC-FPIA) using a non-specific polyclonal antibody. They were also analyzed by HPLC-mass spectrometry (MS) using fast atom bombardment (HPLC-MS-FAB). Five collected fractions gave positive results with FPIA. The major metabolites found were M1, M17 and M21 after identification by HPLC-MS-FAB and comparison with three corresponding standard metabolites. The CsA biotransformation rates were calculated by the amount of unmetabolized CsA and were linear with time. These mean rates (Vm) for 12-min incubation by renal microsomes of rabbits treated with rifampicin or erythromycin or untreated (control) were 0.11, 0.02 and 0.04 nmol/min x mg microsomal protein, respectively. These rates were 15-, 37-, and 30-fold lower than those obtained with hepatic microsomes of rabbits treated identically. As CsA metabolites are less cytotoxic than the parent drug, this weak renal biotransformation of CsA after in vitro incubation should be one of the mechanisms of its in vivo nephrotoxicity.


Calcaneal osteotomies.
The current trend is to preserve the hindfoot joints to allow for more normal biomechanics and avoid arthritic changes in adjacent joints. Calcaneal osteotomies are effective in the treatment of hindfoot and foot malalignment with an acceptable rate of complications at medium-term follow-up. An important prerequisite should be flexibility and the absence of joint arthritis.


Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage.
Proteases, such as tissue plasminogen activator, thrombin, metalloproteinases, and cathepsins, have complex functions in the mammalian brain under both normal and pathological conditions. Some of these proteases are expressed by neuronal cells, whereas others are made by the immunocompetent, macrophage-like cells of the brain: the microglia. This article reviews the physiological and pathological functions of these proteinases in the brain as well as recent findings linking extracellular proteases with neuronal cell death in ischemic or hemorrhagic stroke. Better understanding of protease expression and signaling, microglial activation, and their relationship with neuronal cell death during stroke injury could contribute to the development of relevant inhibitors as novel neuroprotective agents for treating ischemic stroke and intracerebral hemorrhage.


Vigilance, awareness and a phone line: 20 years of expediting CPR for enhancing survival after out-of-hospital cardiac arrest. The 'SHL'-Telemedicine experience in Israel.
The only large-scale report (1988) by the Israeli national ambulance service Magen David Adom (MDA) on the outcome of cardiac arrest victims who underwent cardiopulmonary resuscitation (CPR) by paramedics called for more frequent and more promptly initiated CPR and shorter time to arrival of paramedic care to improve survival. We report the 1987-2007 experience of resuscitation of out-of-hospital cardiac arrest victims who were 'SHL'-Telemedicine subscribers and who underwent CPR by SHL-Telemedicine mobile intensive care units (MICUs) personnel or under their instructions. 'SHL's records of MICU reports and specifics of CPR maneuvers and outcome of resuscitated patients, as recorded by its MICU physicians, were analyzed to determine whether the system enhanced survival. A total of 1810 'SHL'-Telemedicine subscribers (mean age 76+/-12 years [16-104], 67% males) were resuscitated after cardiac arrest, 597 (33%) were hospitalized and 279 (15.4%) were discharged alive. Factors associated with successful resuscitation included witnessed collapse and documented ventricular fibrillation upon MICU arrival. A history of diabetes, hyperlipidemia, stroke or advanced age adversely affected the outcome. Time from collapse to CPR initiation and duration of CPR correlated significantly with survival. Laymen instructed telephonically by the 'SHL'-Telemedicine center performed CPR on 121 patients: 13 (10%) survived to hospital discharge. 'SHL'-Telemedicine's policy of bi-monthly contact with its subscribers led to heightened awareness of warning signs and need for rapid summoning of medical assistance in the setting of out-of-hospital sudden cardiac arrest.


[Hormone-dependent characteristics of the myocyte cell surface in the human myoma and myometrium cultured in diffusion chambers].
The normal and the pathologically changed human myometrium was cultured in the diffusion chamber implanted in the subcutaneous cellular tissue of the rat. In the absence of hormonal influence the growth of myometrium culture is only insignificant, while no myoma cell growth was found at all. Estradiol stimulates the growth and development of the myometrium culture and the myoma. A combined action of estradiol and progesterone stimulates the collagen formation.


AAV-Anti-miR-214 Prevents Collapse of the Femoral Head in Osteonecrosis by Regulating Osteoblast and Osteoclast Activities.
Osteonecrosis of the femoral head, an intractable but common disease that eventually triggers collapse of the femoral head, is characterized by increased osteoclast activity and markedly decreased osteoblast activity in the necrotic region of the femoral head. MicroRNA (miRNA)-214 (miR-214) may play important roles in vertebrate skeletal development by inhibiting osteoblast function by targeting activating transcription factor 4 (ATF4) and promoting osteoclast function via phosphatase and tensin homolog (PTEN). This study revealed significantly increased levels of miR-214 in necrotic regions, with commensurate changes in the numbers of its target cells (both osteoblasts and osteoclasts). To investigate whether targeting miR-214 could prevent femoral head collapse, we constructed an adeno-associated virus (AAV)-associated anti-miR-214 (AAV-anti-miR-214) and evaluated its function in vivo. AAV-anti-miR-214 promoted osteoblast activity and diminished osteoclast activity, effectively preventing collapse of the femoral head in a rat model of osteonecrosis.