Efficacy of Adjunctive Hyperbaric Oxygen Therapy in Osteoradionecrosis.
Osteoradionecrosis (ORN) is a common consequence resulting from radiation in patients with cancer. Presently, hyperbaric oxygen therapy (HBOT) is proposed to have a role in improving wound healing in ORN patients. There is no strong scientific evidence to confirm the benefits of HBOT for treatment of ORN as an adjunctive treatment. This study aimed to determine the benefits of adjunctive treatment of HBOT in ORN. A retrospective study was conducted at the Srinagarind Hospital, the Faculty of Medicine, Khon Kaen University, Thailand, between 2011 and 2017. The patients diagnosed with ORN, who received adjunctive HBOT before the operation, were enrolled. Complete healing of wounds was the primary outcome. There were 84 ORN patients with a mean age of 58.78 years; 54.76% were male and 45.24% were female. HBOT had a role significant in improving wound healing of ORN patients with stages 1 and 2. Poisson regression analysis showed that stage 3 of ORN negatively correlated with the number of HBOT dives (p = 0.001, incidence rates ratio = 0.85). In conclusion, HBOT improved wound healing of ORN patients with stages 1 and 2. In addition, stage 2 of ORN patients significantly required the highest number of HBOT dives compared to other types of ORN to promote wound healing, whereas stage 3 patients, who underwent bone debridement combined with HBOT, initiated to success of treatment process and required a smaller number of dives.


Comparison of efficacy of kinesiological taping and subacromial injection therapy in subacromial impingement syndrome.
The aim of the study was to compare the efficacy of kinesiological taping and subacromial injection therapy in patients with subacromial impingement syndrome (SIS). Seventy patients diagnosed with SIS were randomly assigned to group 1 (n = 35, injection group) or group 2 (n = 35, kinesiological taping group). Betamethasone plus prilocaine was injected to subacromial space in the patients in group 1. In group 2, tape was applied three times for a period of five consecutive days with a 2-day recovery interval. A 3-month exercise program was prescribed for both groups including stretching and strengthening exercises. All patients were assessed at baseline and at 1 and 3 months post-intervention. Assessments were made by visual analog scale (VAS) for pain, range of motion (ROM) measurements, specific tests, and Shoulder Pain and Disability Index (SPADI). Significant differences were detected in VAS and SPADI scores as well as ROM measurements in both groups when compared to baseline (p > 0.05). No significant differences were detected between the groups except for active flexion degree in favor of group 1 (p = 0.004). Both kinesiological taping and steroid injection in conjunction with an exercise program were found to be effective in the treatment of SIS. Kinesio taping may be an alternative treatment option in the rehabilitation of SIS especially when a non-invasive technique is needed.


VEGF as a Survival Factor in Ex Vivo Models of Early Diabetic Retinopathy.
Growing evidence indicates neuroprotection as a therapeutic target in diabetic retinopathy (DR). We tested the hypothesis that VEGF is released and acts as a survival factor in the retina in early DR. Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing DR, that is, high glucose (HG), oxidative stress (OS), or advanced glycation end-products (AGE). Neuroprotection was provided using octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well-documented neuroprotectants. Data were obtained with real-time RT-PCR, Western blot, ELISA, and immunohistochemistry. Apoptosis was induced in the retinal explants by HG, OS, or AGE treatments. At the same time, explants also showed increased VEGF expression and release. The data revealed that VEGF is released shortly after exposure of the explants to stressors and before the level of cell death reaches its maximum. Retinal cell apoptosis was inhibited by OCT and PACAP. At the same time, OCT and PACAP also reduced VEGF expression and release. Vascular endothelial growth factor turned out to be a protective factor for the stressed retinal explants, because inhibiting VEGF with a VEGF trap further increased cell death. These data show that protecting retinal neurons from diabetic stress also reduces VEGF expression and release, while inhibiting VEGF leads to exacerbation of apoptosis. These observations suggest that the retina in early DR releases VEGF as a prosurvival factor. Neuroprotective agents may decrease the need of VEGF production by the retina, therefore limiting the risk, in the long term, of pathologic angiogenesis.


Super-atmospheric pressure ionization mass spectrometry and its application to ultrafast online protein digestion analysis.
Pressure is a key parameter for an ionization source. In this Special Feature article, Lee Chuin Chen and colleagues review super-atmospheric pressure ionization MS with electrospray, corona-discharge-based chemical ionization, and field desorption. They routinely run their mass spectrometer with ion source pressures ranging from several to several tens of atmospheres. A number of strategies have been used to preserve the high vacuum of the instrument while working with a high-pressure (HP) ion source. A recent prototype uses a booster pump with variable pumping speed added to the first pumping stage of the mass spectrometer to regulate a constant vacuum pressure. Further, a new HP-ESI source allowing rapid (a few seconds) online protein digestion MS is also reported. Dr. Lee Chuin Chen is Associate Professor in the Department of Interdisciplinary Research at the University of Yamanashi (Yamanashi, Japan). His main research interest is the development of novel mass spectrometric methods for in-situ medical diagnosis.


Stability of psychological test results in newly admitted alcoholics.
Previous research has demonstrated that psychological test results of newly admitted alcoholics are not stable due to lingering alcohol toxicity. The present study (N = 40) demonstrated that a 10-day delay in testing is sufficient to obtain stable results on some psychological tests.


Comparative Activity of Ciprofloxacin, Levofloxacin and Moxifloxacin against Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia Assessed by Minimum Inhibitory Concentrations and Time-Kill Studies.
The aim of this study was to compare the in vitro susceptibility of Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia to three fluoroquinolones. The minimum inhibitory concentrations (MICs) to ciprofloxacin, levofloxacin and moxifloxacin were examined by E-test® for a total of 40 K. pneumoniae strains, 40 S. maltophilia strains and 40 P. aeruginosa strains. Then, the bactericidal activity of these fluoroquinolones was investigated on five strains of each bacterial species by means of time-kill curves. For K. pneumoniae and P. aeruginosa, the distance of the measured MIC from the clinical break-point is a good indicator of the bactericidal activity for ciprofloxacin and levofloxacin as obtained in our experiments. The lower the MIC, the better the bactericidal activity in term of CFU Log decreases. If MIC of ciprofloxacin and levofloxacin against the considered bacteria are far from clinical breakpoint, these two antibiotics are equivalent. According to our MIC50 and modal MIC, the breakpoints of both ciprofloxacin and levofloxacin seem to be somewhat high and data suggest reducing them. On S. maltophilia, none of the tested antibiotics showed a satisfactory activity.


Disparities in Health Care Coverage Among U.S. Born and Mexican/Central American Born Labor Workers in the U.S.
We examined health insurance coverage among U.S. and Mexican/Central American (M/CA) born labor workers living in the U.S. Using data from the 2010-2015 National Health Interview Survey, we employed logistic regression models to examine health insurance coverage and covariates among U.S. and M/CA born labor workers. Prevalence ratios between U.S. and M/CA born workers were also obtained. U.S. born workers had double the prevalence of insurance coverage. Regarding private insurance coverage, U.S. born workers had a higher prevalence of coverage compared to their M/CA born counterparts. Among foreign born workers with U.S. citizenship, the odds of having insurance coverage was greater than that of noncitizens. Additionally, those who had lived in the U.S. for 10 or more years had higher odds of having health insurance coverage. Disparities in health care coverage exist between U.S. born and foreign born labor workers.


A Simple Chiral Cu(II) Complex as an Effective Phase-Transfer Catalyst for the Enantioselective Alkylation of Dissymmetric Glycinate Ketimines.
Catalytic asymmetric benzylation of a dissymmetric tert-butylglycinate ketimine, incorporating 1-naphthyl and phenyl groups as the Schiff base substituents, under phase-transfer conditions was investigated. It was interesting to note that the sense of asymmetric induction of the alkylation of Z-imine stereoisomer is opposite to that of the corresponding E stereoisomer with a similar degree of enantioselectivity. More interestingly, the chiral Cu(II) complex of the Schiff base derived from (R)-2-phenylglycinol and 2-hydroxy-1-naphthaldehyde was found to catalyze the same reaction under solid-liquid conditions with comparable enantioselectivity (up to 60% ee) with respect to known cinchona alkaloid catalysts. The solvent/base-system parameter was shown to control the optimal catalytic activity.


Burr Hole Drainage : Could Be Another Treatment Option for Cerebrospinal Fluid Leakage after Unidentified Dural Tear during Spinal Surgery?
Authors report a rare case of acute intracranial subdural and intraventricular hemorrhage that were caused by intracranial hypotension resulted from cerebrospinal fluid leakage through an unidentified dural tear site during spinal surgery. The initial brain computed tomography image showed acute hemorrhages combined with preexisting asymptomatic chronic subdural hemorrhage. One burr hole was made over the right parietal skull to drain intracranial hemorrhages and subsequent drainage of cerebrospinal fluid induced by closure of the durotomy site. Among various methods to treat cerebrospinal fluid leakage through unidentified dural injury site, primary repair and spinal subarachnoid drainage are well known treatment options. The brain imaging study to diagnose intracranial hemorrhage should be taken before selecting the treatment method, especially for spinal subarachnoid drainage. Similar mechanism to its spinal counterpart, cranial cerebrospinal fluid drainage has not been mentioned in previous article and could be another treatment option to seal off an unidentified dural tear in particular case of drainage of intracranial hemorrhage is needed.


Experimental studies on human health effects of air pollutants. III. Two-hour exposure to ozone alone and in combination with other pollutant gases.
Adult male volunteers were exposed to ozone (O3) at 0.25, 0.37, or 0.50 ppm, and to O3 in combination with nitrogen dioxide (NO2) and carbon monoxide (CO), with secondary stresses of heat, intermittent light exercise, and repeated exposure. Few important physiological changes, and only mild symptoms, were found with 0.25 ppm O3, with 0.25 ppm 03 plus 0.30 ppm NO2, or when 30 ppm CO was added to the latter mixture. With 0.37 ppm O3, more symptoms were present and some subjects developed definite decreases in pulmonary function. With 0.50 ppm O3, most subjects had symptoms and about half showed substantial pulmonary function decrement. In reactive subjects exposed on two successive days, changes were usually greater the second day, indicating that effects of successive exposures were cumulative.


[Morphological studies of hydroxyapatite crystals exposed to disodium pamidronate].
"In vitro" effects of disodium pamidronate on hydroxyapatite crystals morphology, and some "in vivo" data from bone powder of tibia and vertebrae from treated young and mature rabbits are here reported. Hydroxyapatite, synthesized following Rigoli et al method, and bone powder from rabbits were studied with X-ray, infrared and raman emission techniques for crystallographic analysis. Adsorption studies were also performed with a balanced solution of hydroxyapatite exposed to different times, 48, 120 and 168 hours and concentrations 1 x 10(-5) M, 3 x 10(-5) M, 8 x 10(-5) M y 1 x 10(-4) M of pamidronate. Infrared and raman spectrometry were not conclusive due to technical bias, but X-ray difractograms showed pure hydroxyapatite crystals in an hexagonal system. At constant time, pamidronate concentrations were varied, showing after 48 hours of exposition, a slight growth in the 002 plane, an aleatoric behavior in 213 and a marked increase in 004. After 120 hours, 002 plane is steady with a net growth in 004 and 213. After 168 hours, the 3 mentioned planes grow in proportion to pamidronate concentrations, tending to enlarge the crystal shape. Plane 13 markedly grow with pamidronate 8 x 10(-5) M a 1 x 10(-4) M, which are biologically high concentrations. Potentiometric assessments, in the 1 x 10(-5) to 1 x 10(-4) M range of concentrations show that bisphosphonate was completely adsorbed to the crystals. Additional "in vivo" observations showed changes in bone powder crystals isolated from pamidronate treated young animals, involving a growing of planes 002 and 211, in samples from both epiphysis and diaphysis, regarding untreated samples. Changes were more evident at epiphysis. In mature rabbits, it was shown a decrease in basal plane 002 and growing at 210, 211 and 310 with a trend to enlarge the crystal shape in diaphysis and to shorten it in vertebrate spongiosa. The "in vivo" doses are equivalent to those used by Ferretti et al. in intact rats with pamidronate low dose groups, showing an improvement of bone material properties and stiffness. Thus, it may rather be lower than the "in vitro" used concentrations. In concordance with above experimental conditions it can be concluded that bisphosphonates exert morphological changes in hydroxyapatite crystals, in a dose dependent manner, at least when high concentrations are used. In addition, it is postulated that changes observed on "in vivo" samples may be the result with other adaptative factors as for example the local mechanical usage. The latter data were limited, and should be studied with more details if an extrapolation to the bisphosphonate treated osteoporotic women is intended. Finally, it is suggested that any agent that changes BMU activity (all known anti-osteoporotic drugs) may potentially modify the quality of hydroxyapatite crystals, affecting in turn the bone resistance to fracture, independently from the quantity of bone mass gained. Thus, to help predicting the consequences on skeletal fragility, there is a need to know the direct or indirect effect of drugs on bone crystals.


Exogenous neutrophil elastase enters bronchial epithelial cells and suppresses cigarette smoke extract-induced heme oxygenase-1 by cleaving sirtuin 1.
An imbalance between oxidative stress and antioxidant activity plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke, a major risk factor of COPD, induces cellular oxidative stress, but levels of antioxidants such as heme oxygenase-1 (HO-1) are reduced in individuals with severe COPD. In this study, we evaluated the molecular mechanism of reduced HO-1 expression in human bronchial epithelial cells. We found that cigarette smoke extract (CSE) increases HO-1 levels via activation of NFE2-related factor 2 (Nrf2). However, pretreating cells with the protease neutrophil elastase (NE) suppressed the CSE-induced expression of HO-1 mRNA and protein. NE also decreased the sirtuin 1 (SIRT1) level, but did not inhibit CSE-induced nuclear translocation and DNA-binding activity of Nrf2. Transfection of cells with a Myc/His-tagged SIRT1 expression vector completely blocked the NE-mediated suppression of HO-1 expression. We further noted that the NE-induced down-regulation of SIRT1 was not due to decreased transcription or proteasomal/lysosomal degradation or loss of solubility. Immunofluorescence staining revealed that NE enters the cell cytoplasm, and we observed that NE directly cleaved SIRT1 in vitro, indicating that SIRT1 levels are decreased via direct degradation by internalized NE. Of note, we observed decreased SIRT1 levels in NE-treated primary human bronchial epithelial cells and in lung homogenates from both smokers and patients with COPD. In conclusion, NE suppresses CSE-induced HO-1 expression by cleaving SIRT1. This finding indicates the importance of cross-talk between oxidative stress and protease responses in the pathogenesis of COPD.


Integrating two epistemological goals: why shouldn't we give it another chance?
As Beller, Bender, and Medin (in press) pointed out in their target article, in the contemporary study of culture in psychology, anthropology is virtually invisible. In this commentary, I traced this invisibility to a root conflict in epistemological goals of the two disciplines: Whereas anthropologists value rich description of specific cultures, psychologists aspire to achieve theoretical simplicity. To anthropologists, then, to understand culture is to articulate symbolic systems that are at work in a given location at a given time. In contrast, to psychologists, to understand culture amounts to identifying socio-cultural variables that moderate psychological effects. These divergent epistemological goals dictate both theoretical perspectives and empirical approaches in both disciplines. Yet, the two goals are both valid and in fact complementary. A renewed effort toward integration of the two goals may enrich both disciplines.


Infantile NTRK-associated Mesenchymal Tumors.
Pediatric fibroblastic/myofibroblastic lesions are a relatively common group of tumors with varying morphologies, for which the molecular mechanisms are becoming increasingly well characterized. Congenital infantile fibrosarcoma (CIFS), perhaps the most well studied of these lesions is characterized by a recurrent ETV6-NTRK3 gene fusion. However, a notable subset of locally aggressive congenital/infantile soft tissue lesions with similar morphologic features to CIFS, have not to-date, shown evidence of any canonical molecular aberration. We describe 6 patients with mesenchymal tumors composed of infiltrative fibroblastic/myofibroblastic tumor cells and showing a morphologic spectrum of features much analogous to that previously described in CIFS but without ETV6 fusion transcripts. These tumors lacked a uniform immunoprofile, but showed variable expression of CD34, S100, smooth muscle actin, and CD30. All patients first developed a mass in infancy (≤2 months of age). Using next-generation DNA sequencing, TMP3-NTRK1 fusions were identified in 4 cases, an LMNA-NTRK1 fusion in one case, and a variant EML4-NTRK3 fusion in one case. Similar to infantile fibrosarcoma, these tumors were locally aggressive (with local recurrences if incompletely excised) and rarely metastasized (lung metastases in one patient). Proper identification of these tumors including investigation for NTRK family gene rearrangements is essential for diagnostic accuracy, as well as for clinical management decisions. Given the morbidity associated with radical resection of large soft tissue tumors, children with unresectable, recurrent, and/or metastatic disease may benefit from treatment with NTRK targeted therapies.


Cardiac troponin T release and inflammation demonstrated in marathon runners.
As shown on the basis of highly sensitive assays, cardiac troponin release is now observed after physiological heart stress and in mild heart pathologies: both are [corrected] considered unrelated to the irreversible cardiac alteration that is typically the source of release. Transitory cardiac membrane leakage was suggested as the basis. In our view, mild inflammation may drive this type of cardiac troponin release. To verify this hypothesis, marathon runners who demonstrated post-run inflammation were used as a model to correlate cTnT release and inflammation intensity. In 78 male marathon runners who participated in the BERLIN-MARATHON 2006, cardiac troponin T (cTnT) was monitored [corrected] at three time points (pre-race, post-race, and after two weeks of rest). [corrected] Measurements were done with the highly sensitive assay (hs cTnT assay) and the conventional fourth-generation cTnT assay for comparison. Concurrently, [corrected] the inflammation markers (leukocyte and neutrophil counts, CRP, IL-6) were measured. Pre-race, the fourth-generation assay failed to demonstrate cTnT positivity (> test specific LLD). In contrast, with the [corrected] use of the highly sensitive assay, 28% of the participants were positive for cTnT (> LLD of hs cTnT assay). Post-race, cTnT as measured with the fourth-generation assay was observed to be detectable in 43% of the runners (> LLD = 99(th) percentile cut off), but all runners had detectable cTnT values (> LLD) when measured with the highly sensitive assay. Even in 94% of these cTnT-positive runners, the value exceeded the 99(th) percentile cut off determined for the highly sensitive assay (13 ng/L). cTnT release correlated significantly with inflammation intensity. Faster runners demonstrated significantly stronger cTnT releases and inflammation signs. As demonstrated after physiological heart stress such as marathon running, transitory inflammation is evidently one of the events contributing to the cardiac troponin release under conditions suggested as unrelated to irreversible cardiac alteration.


Principles of receptor-based inhibition of erbB family receptor kinases: prospects for new therapies for human cancers.
The erbB family of receptor tyrosine kinases is composed of growth factor receptors that are overexpressed or mutated in a large variety of human cancers. The study of erbB-mediated signal transduction will lead to an understanding of the role played by this family of receptors in normal and transformed cells. In this article, we discuss the contemporary understanding of the structure and function of these receptors and how these features might be exploited in receptor-based strategies of growth inhibition. The first part of our study details the structure of erbB receptors as it relates to the process of transformation of cells and the malignant phenotype in humans. In the second part, we discuss two rational approaches to therapy for cancers in which erbB receptors are overexpressed or mutated: first, the potential for antireceptor immunity and the evolution of small molecules for receptor-based immunotherapy; second, a strategy of ectodomain association that leads to the formation of defective kinase assemblies. These studies provide a basis for the application of receptor-based strategies of growth inhibition in erbB-expressing human cancers.


Ptf1a triggers GABAergic neuronal cell fates in the retina.
In recent years, considerable knowledge has been gained on the molecular mechanisms underlying retinal cell fate specification. However, hitherto studies focused primarily on the six major retinal cell classes (five types of neurons of one type of glial cell), and paid little attention to the specification of different neuronal subtypes within the same cell class. In particular, the molecular machinery governing the specification of the two most abundant neurotransmitter phenotypes in the retina, GABAergic and glutamatergic, is largely unknown. In the spinal cord and cerebellum, the transcription factor Ptf1a is essential for GABAergic neuron production. In the mouse retina, Ptf1a has been shown to be involved in horizontal and most amacrine neurons differentiation. In this study, we examined the distribution of neurotransmitter subtypes following Ptf1a gain and loss of function in the Xenopus retina. We found cell-autonomous dramatic switches between GABAergic and glutamatergic neuron production, concomitant with profound defects in the genesis of amacrine and horizontal cells, which are mainly GABAergic. Therefore, we investigated whether Ptf1a promotes the fate of these two cell types or acts directly as a GABAergic subtype determination factor. In ectodermal explant assays, Ptf1a was found to be a potent inducer of the GABAergic subtype. Moreover, clonal analysis in the retina revealed that Ptf1a overexpression leads to an increased ratio of GABAergic subtypes among the whole amacrine and horizontal cell population, highlighting its instructive capacity to promote this specific subtype of inhibitory neurons. Finally, we also found that within bipolar cells, which are typically glutamatergic interneurons, Ptf1a is able to trigger a GABAergic fate. Altogether, our results reveal for the first time in the retina a major player in the GABAergic versus glutamatergic cell specification genetic pathway.


[Efficacy and safety of the TAIS coronary stent implantation: nine month multicenter study].
Assessment of clinical and angiographic results of a balloon-expandable steel matrix stent TAIS in patients with atherosclerosis of the coronary arteries with no history of previous interventions in the course of an open non-randomized multicenter trial. The TAIS stent was implanted in 187 patients into 199 stenoses. 47% patients had clinical manifestations of unstable angina pectoris. 29% cases were complicated. The length of the stenoses reached 11.3 +/- 5.4 mm, 22% stenoses were prolonged. This coronary stenting was effective in 100% cases, neither acute nor subacute thromboses were seen. Myocardial infarction without occlusion of the stent developed in 3 patients. The incidence of cardial complications (death, angina, restenosis, repeated revascularization) in 6 month follow-up was 11.8%. An angiographic control in 6 months was made in 184 patients (194 stenoses). The vascular diameter loss index was 0.40 +/- 0.21, a restenosis level--10.7%. A logistic regression analysis has revealed significant correlations between the length of the stent and a target vascular diameter with subsequent restenosis. Repeated revascularization was performed in all the patients with stent restenosis. After control angiography cardiac complications developed in 13.9% patients. Nine month follow-up registered cardiac complications in 17.6% cases. The TAIS stent was found effective in prevention of thrombosis and restenosis in patients with a relatively high risk of intervention.


Geographic coincidence of increased malaria transmission hazard and vulnerability occurring at the periphery of two Tanzanian villages.
The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection.


Does Abeta 42 have a function related to blood homeostasis?
In this review, I discuss the possibility that Abeta42 has a physiologic function in blood vessel homeostasis and the consequences that this might have for theories concerning the pathogenesis of Alzheimer's disease and for treatment.


12-Oxophytodienoate Reductase Overexpression Compromises Tolerance to Botrytis cinerea in Hexaploid and Tetraploid Wheat.
12-Oxophytodienoate reductase is the enzyme involved in the biosynthesis of phytohormone jasmonates, which are considered to be the major regulators of plant tolerance to biotic challenges, especially necrotrophic pathogens. However, we observe compromised tolerance to the necrotrophic fungal pathogen Botrytis cinerea in transgenic hexaploid bread wheat and tetraploid emmer wheat plants overexpressing 12-OXOPHYTODIENOATE REDUCTASE-3 gene from Arabidopsis thaliana, while in Arabidopsis plants themselves, endogenously produced and exogenously applied jasmonates exert a strong protective effect against B. cinerea. Exogenous application of methyl jasmonate on hexaploid and tetraploid wheat leaves suppresses tolerance to B. cinerea and induces the formation of chlorotic damages. Exogenous treatment with methyl jasmonate in concentrations of 100 µM and higher causes leaf yellowing even in the absence of the pathogen, in agreement with findings on the role of jasmonates in the regulation of leaf senescence. Thereby, the present study demonstrates the negative role of the jasmonate system in hexaploid and tetraploid wheat tolerance to B. cinerea and reveals previously unknown jasmonate-mediated responses.


The first 60 years: Honoring Teratology's past, a new perspective on the future.
This paper updates the history of the Teratology Society, now known as the Society for Birth Defects Research and Prevention (BDRP), for its first 60 years and describes the current strategy to position the Society to continue to advance its multidisciplinary science in the future. Common threads across our history include the positive impact of the Society's approach to sharing multidisciplinary, cutting-edge science and the collegial nature of the annual meetings. In recent years, we have tackled challenging issues through periodic strategic planning sessions to improve the impact of the Society and its value to our members. Archived and current resources were reviewed for this historical perspective. In 2019, the Society took steps to rebrand itself to clarify our mission to the broader scientific and governmental communities. Although our name has changed, the mission remains to understand and prevent birth defects and disorders of developmental and reproductive origin. As BDRP, we continue to promote the exchange of research and ideas, provide educational opportunities, influence policy through advocacy, and evolve our communications to better serve our members and to have a greater impact on the health of future generations.


Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine.
The serotonin receptor type 3 is a pentameric ligand-gated ion channel regulating intestinal motility, nausea, and vomiting in humans. The HTR3B gene codes for the subunit B of this receptor. The HTR3B transcription start site is not unequivocally identified. In the present study we used transcription start site analyses, transcript-specific RT-PCR, and functional promoter analyses to identify the 5' structure of the HTR3B gene. According to these experiments, two alternative promoters control the expression of different HTR3B transcripts in the peripheral and central nervous system. The transcription start sites observed in the intestine corresponded to the current human genome annotation (NCBI Build 36.1, March 2006). The transcription start sites in the brain, however, were localized in a region about 4000 bp downstream. The brain transcripts lacked the coding first exon of the HTR3B structure published earlier but had an upstream-extended exon 2 containing a new potential translational start site. Reporter gene analyses showed significant promoter activity of the genomic region located 1560 bp upstream to 93 bp downstream of the brain-specific transcription start sites. This data suggests a different transcriptional regulation of the HTR3B gene in the peripheral and the central nervous system that leads to the expression of transcripts with variations in the 5' coding sequence. Further studies on the expression, structure and function of therefore expected tissue-specific 5-HT(3B) isoforms are required.


Clinical characteristics, microbiology and outcomes of external ventricular drainage-associated infections: The importance of active treatment.
Data concerning clinical characteristics, microbiology, treatment and outcomes of external ventricular drainage-associated infections (EVDAI) are limited. All hospitalized patients with EVDAI in a University Hospital between January 2009 and December 2015 were retrospective recorded. Only the first episode per patient was included. An antibiotic was considered "active" when its pharmacokinetic properties were appropriate for EVDAI and the implicated microorganism was in vitro susceptible. During the 7-year study period, 36 EVDAI were identified. Median patient age was 53years and 23 (63.9%) were male. Catheter types were intraventricular (70.6%) and lumbar (29.4%). Median catheterization duration before infection was 14days. Gram-negative bacteria (GNB) predominated (57.9%), followed by gram-positives (36.8%) and fungi (5.3%). Administered antibiotics were considered "active" in 69.4% of empirical and in 86.1% of definitive treatment regimens. In 10 infections, intraventricular/intrathecal (IVT) antibiotics were administered. Eleven patients died (30.6%) during hospitalization. Patients who died had higher rates of EVDAI by GNB (p=0.011) and higher rates of treatment with intravenous colistin (p=0.019 for empirical and p=0.006 for definitive colistin). Compared to EVDAI by other pathogens, patients with EVDAI by GNB had longer catheter-days before infection (p<0.001) and higher mortality (p=0.011). In our study, GNB were a frequent cause of EVDAI, and were related with high rates of inactive treatment and mortality. Intravenous colistin alone is not effective and treatment should include IVT antibiotics and intravenous antibiotics that achieve adequate CSF levels.


Integrated morphologic and molecular analysis of Trichomonas vaginalis, Mycoplasma hominis, and human papillomavirus using cytologic smear preparations.
Pathogenic microbes may colonize the female genital tract via sexual transmission and cause health issues like inflammation or malignancy, summarized as sexually transmitted disease (STD). A major representative of such pathogens is Trichomonas vaginalis (T.v.), whose role in the etiology of cervical cancer remains elusive. Traditional morphologic screening of cervical smears is able to detect T.v., although its identification may be complicated by look-alikes such as degenerated granulocytes and basal cells. In addition, the parasite's endosymbiont Mycoplasma hominis (M.h.) cannot be detected in the Pap test. This investigation was aimed at designing a PCR-based method to detect specific pathogenic germs by using cervical cytology slides to overcome morphologic uncertainty and increase diagnostic accuracy. To test our molecular screening method on T.v., M.h., and HPV in archival smears, we elaborated a multiplex PCR approach based on microdissection. This assay was applied to a minute quantity of starting material which harbored or was suspected to harbor T.v.; the resulting isolated DNA was used for subsequent molecular analyses of T.v., M.h., and HPV. We clarified the diagnosis of genital T.v. infection in 88 and 1.8% of morphologically suspicious and T.v.-negative cases, respectively. We also revealed a tendency of M.h. co-infection in high-risk HPV cases. In conclusion, a microdissection-based approach to detect pathogenic microbes such as T.v., HPV, and M.h. is a molecular tool easy to implement and may help to better understand the interactivity of these germs with respect to pathogenesis.


[Alpha amylase and dehydrogenase activity in suboptimal Ni intake].
Supplementary to studies on the activity of various enzymes during Ni deficiency, the present work was done to determine their response to suboptimal Ni supply. Live weight gain of rats was not affected by 60 versus 150 ppb Ni in the diet. The activity of alpha-amylase, however, was reduced by 43% in the case of 60 ppb dietary Ni and in relation to the change in this enzyme the activity of glucose-6-phosphate dehydrogenase by 56% and of the lactate dehydrogenase by 27%. These dehydrogenases responded with increased activities to the slight raise in Ni supply with the diet containing 150 ppb Ni as compared to the group given 60 ppb dietary Ni. Overall, it may be inferred that growth is not affected unless dietary Ni supply is below 50 ppb and that dietary Ni contents of 60 and 150 ppb must be regarded as suboptimal supply levels because of the diminished activity of various enzymes.


Measurement of apoptosis by SCAN©, a system for counting and analysis of fluorescently labelled nuclei.
Apoptosis-like programmed cell death (A-PCD) is a universal process common to all types of eukaryotic organisms. Because A-PCD-associated processes are conserved, it is possible to define A-PCD by a standard set of markers. Many of the popular methods to measure A-PCD make use of fluorescent ligands that change in intensity or cellular localization during A-PCD. In single cell organisms, it is possible to quantify levels of A-PCD by scoring the number of apoptotic cells using flow cytometry instruments. In a multicellular organism, quantification of A-PCD is more problematic due to the complex nature of the tissue. The situation is further complicated in filamentous fungi, in which nuclei are divided between compartments, each containing a number of nuclei, which can also migrate between the compartments. We developed SCAN©, a System for Counting and Analysis of Nuclei, and used it to measure A-PCD according to two markers - chromatin condensation and DNA strand breaks. The package includes three modules designed for counting the number of nuclei in multi-nucleated domains, scoring the relative number of nuclei with condensed chromatin, and calculating the relative number of nuclei with DNA strand breaks. The method provides equal or better results compared with manual counting, the analysis is fast and can be applied on large data sets. While we demonstrated the utility of the software for measurement of A-PCD in fungi, the method is readily adopted for measurement of A-PCD in other types of multicellular specimens.


Traumatic injuries of children and adolescents--are they associated with psychiatric contacts?
Our aim was to investigate whether a large number of hospital visits by children and adolescents because of injuries are associated with psychiatric treatments and subsequent suicides. We examined the case records of 250 randomly chosen patients, 156 (62%) boys and 94 (38%) girls, out of 2306 outpatients who were 0-16 years old and had been treated because of traumatic injuries in Oulu University Hospital in 1984 and were alive in 1997. Boys with seven or more accidents had had psychiatric treatments more commonly than did boys with fewer accidents (39% vs. 8%). In addition, the case records of the patients who had died before the end of 1997 out of the 2306 patients were examined. Twenty-one (0.9%) patients (20 males and one female) had died, and seven (0.3%) of them had committed suicide. The traumatically injured male patients had a twofold suicide rate compared to the national average. The researchers also re-coded the causes of death from the death certificates. There seems to be a tendency to interpret adolescent suicides as accidental, as one of the seven registered suicides (14%), but six of the seven re-coded suicides (86%) had occurred before the age of 20.


Ultrastructural changes in neonatal liver tissue: effects of maternal drinking.
There is already sufficient evidence in the literature that alcohol abuse during pregnancy has a toxic effect upon the developing fetus; however, previous studies have not revealed any morphological changes in fetal or newborn liver specimens from animals exposed to alcohol in utero. As it is known that alcohol freely crosses the placental barrier, this investigation was an attempt to demonstrate that structural abnormalities can indeed be identified in neonatal mouse liver specimens from pups exposed to alcohol in utero. Chosen as a model for this study was the C57BL/KsJ mouse strain as this particular animal demonstrates an alcohol preference paralleling that of the human alcoholic. Findings appear to indicate the presence of abnormal changes on the morphological level in these study animals.


A confocal and conventional epifluorescence microscope study of the intermediate filaments in chorionic villi.
An immuno-epifluorescence microscopic study of first trimester human chorionic villi has revealed different patterns of distribution for intermediate filament proteins. Keratin staining was restricted to the trophoblastic epithelium. The protein was shown to be concentrated into desmosome-containing apical and basal cytoplasm. Strands of keratin-rich cytoplasm extended across the interior of the syncytium, integrating basal and apical layers. This arrangement integrates the epithelial cytoskeleton in a manner well adapted to resisting shearing forces. Vimentin was found in the cells of the villous core and was most strongly expressed in endothelial cells. Desmin was also restricted in distribution of spindle-shaped cells of the villous core. It was excluded from terminal villi.


Tyrosine 70 fine-tunes the catalytic efficiency of aspartate aminotransferase.
The aspartate aminotransferase mutant Y70F exhibits kcat = 8% and kcat/KM = 2% of the wild type values for the transamination of aspartate and alpha-ketoglutarate. The affinity of the enzyme for the noncovalently bound inhibitor maleate is reduced 17-fold by the mutation, while only a 2.5-fold reduction is observed for alpha-methylaspartate, which forms a stable, covalent external aldimine. The high population of the quinonoid intermediate formed in the reaction of the wild type with beta-hydroxyaspartate is more than 75% diminished by the mutation. The values of the Y70F C alpha-H kinetic isotope effects for the aspartate reaction are larger than those of wild type (DV = 2.4 vs 1.52; D(V/K) = 2.5 vs 1.7). Conversely, the Y70F value of D(V/K) for the glutamate reaction is decreased compared to wild type (1.75 vs 2.5). These results, combined with previous studies of Lys258 mutants, eliminate Tyr70 as an essential component of the catalytic apparatus, with the caveat that the functionally of the deleted hydroxyl group is possibly replaced by a water molecule.


Effects of acute, angiotensin-induced hypertension on intrarenal arteries in the rat.
A perfusion-fixation and vascular casting technique was used to assess the effects of acute, angiotensin-induced hypertension on the intrarenal arteries and, for comparison, the small arteries of the intestine. The first objective was to establish that the technique accurately preserves postmortem the vascular changes induced by acute hypertension. To do this, the easily accessible intestinal arteries were examined and photographed both in vivo and after fixation and injection of Batson's no. 17 casting resin in a group of angiotensin-treated rats and controls. The second objective was to apply the technique to observe and compare acute hypertensive changes in the intrarenal and intestinal arteries; studies included scanning electron microscopy of vascular casts and transmission electron microscopy of vessel walls using ferritin as a tracer to assess permeability. In the angiotensin-treated rats, casts of both intrarenal and intestinal arteries showed many well-defined zones of constriction and nonconstriction. Transmission electron microscopy of both the smaller intrarenal (interlobular) arteries and intestinal vessels revealed focal smooth muscle rarefaction and abnormal permeability to ferritin, found only in the nonconstricted zones. This study provides new evidence that in the kidney, as in the intestine, acute hypertension produces a characteristic pattern of arterial constriction and nonconstriction, and that hypertensive vascular lesions with accompanying increased permeability occur exclusively in the nonconstricted zones.


Occurrence of Clostridium difficile in seasoned hamburgers and seven processing plants in Iran.
The recent increment of the incidence of Community Associated Clostridium difficile Infection (CA)-CDI has led to speculation that this disease is associated to foodborne transmission. Therefore it is critical to establish the community sources of CDI in order to implement the appropriate interventions. The present study was conducted to evaluate the prevalence of C. difficile in seasoned hamburger and examine the sources of C. difficile dispersal in hamburger processing plants. A total of 211 samples including hamburger ingredients, the final product, processing equipment and food contact surfaces were collected from seven hamburger processing plants to evaluate the routes of dispersal of C. difficile. The samples were assessed for the occurrence of C. difficile using culture and polymerase chain reaction (PCR) methods. All isolates were screened for the existence of toxin A, B and binary toxin genes. In addition, isolates were subjected to PCR ribotyping. Overall, 9/211 (4.2%) samples were positive. Toxigenic C. difficile were detected from 2/7 (28.5%) hamburger processing plants, in (3/54) 5.6% of beef meat samples, (2/56) 3.5% of swabs taken from the environment and (4/56) 7.1% of hamburger samples after both molding and freezing. C. difficile was not found in 45 non-meat ingredients including 14 defrosted onions, 14 textured soy proteins and 17 seasonings. All isolates contained tcdB gene while 7 strains were positive for tcdA and two remaining strains were negative for tcdA. None of the isolates harbored binary toxin gene (cdtB). PCR ribotyping of 9 isolates categorized into four ribotypes (IR21, IR 22, IR 23 and IR24). Ribotype IR 22 was the most common type 6/9 (66.6%) found. This genotype was isolated from raw meat, environmental samples and hamburger after both forming and freezing in one processing plant, suggesting raw beef meat as a possible major source of contamination. Hyper-virulent strains of ribotype were not found in this study however, occurrence of other toxicgenic strains indicate the public health significance of contamination of this product.


Genetic organization and evolution of the cryptic plasmid of Neisseria gonorrhoeae.
Three promoters have been identified on the phenotypically cryptic plasmid of Neisseria gonorrhoeae that can direct transcription in Escherichia coli. These promoters do not seem to function at a detectable level when N. gonorrhoeae is grown in vitro under normal growth conditions. The T7 RNA polymerase expression system has been used to identify the proteins encoded by this plasmid, and a series of subclones were constructed and used to localize the gene encoding each protein. In a search of the sequence databases, we have discovered that the derived amino acid sequence of a 1.2-kb segment of the plasmid shows a high degree of sequence similarity to the Mob proteins encoded by the colicinogenic plasmids ColA, ColE1, and ColK of E. coli. The 1.2-kb segment contains part of a Col mobilization region that has subsequently been inactivated by a small duplication. During the recombination event that formed the cryptic plasmid one of the mobilization genes was fused to a cryptic plasmid open reading frame to form the cppB gene. Despite the manner in which it was formed, we have shown that the cppB gene can be expressed when N. gonorrhoeae is grown under the appropriate environmental conditions.


Prognostic Value of Lymph Node Ratio in Breast Cancer Patients with Adequate Pathologic Evidence After Neoadjuvant Chemotherapy.
BACKGROUND The prognostic role of axillary lymph node ratio (LNR) after neoadjuvant chemotherapy (NAC) in breast cancer has not been illuminated. This study was designed to investigate the prognostic role of LNR in breast cancer compared with traditional ypN stage. MATERIAL AND METHODS A total of 306 breast cancer patients diagnosed with positive axillary lymph nodes from January 2007 to December 2014 were eligible for this retrospective analysis. All enrolled patients were treated with a median of 4 cycles of NAC followed by mastectomy and level I, II, and III axillary lymph node dissection (ALND). RESULTS The median duration of follow-up was 78 months (range, 7-147 months). Univariate analysis indicated that both the LNR category (P<0.001) and ypN stage (P<0.001) were significant associated with event-free survival (EFS) and overall survival (OS). However, multivariate analysis indicated that the LNR category was independently associated with EFS (P<0.001) and OS (P<0.001), while the ypN stage showed no statistical effect on EFS (P=0.391) or OS (P=0.081). On additional analyses stratified by molecular subtypes, we found that the prognosis of triple negative breast cancer could be better discriminated when the cutoff value of LNR was set at 0.15. CONCLUSIONS LNR showed a superior predictive value in evaluating prognosis of breast cancer patients after NAC. In addition, the LNR cutoff point 0.15 can accurately discriminate survival outcomes for different triple negative breast cancer subtypes.


In vitro interaction of opioid peptides with phospholipids. Formation and characterization of complexes.
Interaction of Leu- and Met-enkephalin with phosphatidylserine has been studied by chromatographic and spectrophotometric techniques. The main results of our investigation may be summarized as follows: i) Both enkephalins bind to phosphatidylserine; ii) no difference between the two enkephalins is noticeable; and iii) with both peptides the binding phenomenon leads to the formation of two complexes with a definite stoichiometry which are sterically much smaller than the original vesicles. On the basis of the submitted data, a tentative model of the newly formed complexes is provided.


Usability study on two handheld computers to retrieve drug information.
Objective :Performing a usability study on two handheld computers (personal digital assistant and tablet PC), as tools for retrieving drug information. A randomised crossover study was performed: 34 students in pharmacy and medicine used the two handheld tools in a randomised order, to answer a questionnaire containing 12 questions covering all the aspects of a drug database and a qualitative analysis on six different items to measure access to drug information. The availability of the drug information database Vidal on PDA and on tablet PC implied our choice of the database. Three main criteria for evaluation were chosen: success rates, time-on-task, and number of clicks. There were no significant differences between the two groups neither on age, sex, medical discipline, study years nor previous computer practice. The success rate is significantly higher with the PDA for only one question. The PDA is significantly faster than the tablet PC on 7 of the 12 questions and generates fewer clicks for 3 questions. Compared to the tablet PC, it appears that the PDA is better in terms of clearness, navigability and usefulness for professional practice and it is the only tool which is significantly preferred to all other supports. In this study with students, the PDA is significantly more effective quantitatively and qualitatively than the tablet PC to retrieve drug information.


Maintaining mucosal immunity during parenteral feeding with surrogates to enteral nutrition.
Pneumonia and intra-abdominal abscesses are significantly lower in trauma patients receiving enteral feeding compared with those receiving parenteral feeding. Extensive experimental evidence suggests that this is related to maintenance of the mucosal-associated lymphoid tissue, which provides immunologic protection for both the gastrointestinal and respiratory tracts against microbial flora and infectious pathogens. This system is exquisitely sensitive to the route and type of nutrition delivery that affects its functional effectiveness. Although parenteral nutrition decreases the effectiveness of this extraintestinal mucosal immunity, specialty nutrients like glutamine and neuropeptides such as gastrin-releasing peptide and cholecystokinin are capable of preventing some of the immune defects associated with parenteral nutrition. This review examines the mechanisms associated with the mucosal immunity and role of both glutamine and neuropeptides in normalizing defects induced by parenteral feeding. Based upon evolving data, specific nutrients and products of the enteric nervous system show promise as adjuncts to parenteral feeding that are capable of maintaining immune function in patients unable to be fed via the gastrointestinal tract.


Combining field experiments and predictive models to assess potential for increased plant diversity to climate-proof intensive agriculture.
Agricultural production systems face increasing threats from more frequent and extreme weather fluctuations associated with global climate change. While there is mounting evidence that increased plant community diversity can reduce the variability of ecosystem functions (such as primary productivity) in the face of environmental fluctuation, there has been little work testing whether this is true for intensively managed agricultural systems. Using statistical modeling techniques to fit environment-productivity relationships offers an efficient means of leveraging hard-won experimental data to compare the potential variability of different mixtures across a wide range of environmental contexts. We used data from two multiyear field experiments to fit climate-soil-productivity models for two pasture mixtures under intensive grazing-one composed of two drought-sensitive species (standard), and an eight-species mixture including several drought-resistant species (complex). We then used these models to undertake a scoping study estimating the mean and coefficient of variation (CV) of annual productivity for long-term climate data covering all New Zealand on soils with low, medium, or high water-holding capacity. Our results suggest that the complex mixture is likely to have consistently lower CV in productivity, irrespective of soil type or climate regime. Predicted differences in mean annual productivity between mixtures were strongly influenced by soil type and were closely linked to mean annual soil water availability across all soil types. Differences in the CV of productivity were only strongly related to interannual variance in water availability for the lowest water-holding capacity soil. Our results show that there is considerable scope for mixtures including drought-tolerant species to enhance certainty in intensive pastoral systems. This provides justification for investing resources in a large-scale distributed experiment involving many sites under different environmental contexts to confirm these findings.


Preoperative intra-aortic balloon pumping in high-risk cardiac surgery patients.
Intra-aortic balloon pumping increases myocardial oxygen supply and decreases myocardial oxygen demand by inflation and deflation of the balloon. This leads to increased perfusion of the coronary arteries during diastole. This technology has been used for critically ill cardiac patients for more than 30 years. The literature suggests that preoperative use of an intra-aortic balloon pump can be effective in high-risk coronary artery bypass grafting patients. Preoperative benefits of this technology may yield positive outcomes in terms of hemodynamic effect, decreased length of stay in both the intensive care unit and the hospital, and the reduction of complications. However, the intra-aortic balloon pump must be used with a profound understanding of proper mechanism and function, monitoring, and observation for potential complications. This requires excellent critical care nursing management.


C. L. Oakley Lecture (1993). Cellular and molecular aspects of hepatic fibrosis.
Hepatic fibrosis, a consequence of most forms of chronic liver disease, is a dynamic process involving complex interactions between several cell types, the net result of which is accumulation of several distinct extracellular matrix (ECM) proteins. The resultant disruption of intrahepatic blood flow contributes to the development of portal hypertension. The effects, however, are not merely a space-occupying phenomenon; by changing the composition of the ECM, fibrosis may also alter hepatocyte function via cellular integrins. The principal source of ECM proteins in normal and fibrotic liver is the perisinusoidal cells which lie in the space of Disse. The response of this cell population to acute and chronic liver injury has been studied in detail. Perisinusoidal cells proliferate and become activated following hepatocyte necrosis. This phenomenon is transient in acute injuries, but in chronic liver disease, continued activation is associated with phenotypic modulation of perisinusoidal cells to myofibroblasts. This process is mediated by various cytokines including TGF-beta and PDGF. Some of the growth factors involved are derived from activated Kupffer cells and there is evidence of a complex interplay between mediators; injured sinusoidal endothelial cells and platelets are possible additional sources. Accumulation of ECM proteins in fibrosis can be explained not only by increased synthesis, but also by decreased degradation. There is growing evidence that in fibrotic liver there is decreased interstitial collagenase activity. This is, at least in part, due to expression of a tissue inhibitor of metalloproteinase, TIMP-1, by activated perisinusoidal cells.


Inhibitory effect of lipopolysaccharide on immune response after DNA immunization is route dependent.
The DNA prepared from E. coli contained high levels of lipopolysaccharide (LPS). When antigen-encoding DNA was injected into mice, toxicity and increased IgM responses were observed. A method for purifying high yields of DNA (up to 12 mg/L of broth culture) with very low levels of LPS (0.05 ng/mg) was developed. When this purified DNA was used for immunization studies, the toxicity and increased IgM responses were abrogated. Thus, LPS was added to DNA in order to examine its influence on the IgG and cytotoxic T lymphocyte (CTL) response after intramuscular (i.m.) or intradermal (i.d.) DNA immunization. The IgG response to DNA-encoded antigen was inhibited in a dose-dependent manner by the i.d., but not the i.m., route of immunization. Surprisingly, no effect on the CTL response was observed. Therefore, the ability to produce high yields of plasmid DNA with very low levels of endotoxin contamination is advantageous for DNA immunization studies, not only for toxicologic but also for immunologic considerations. Furthermore, these results provide further evidence that immune induction occurs via different mechanisms after i.m. and i.d. DNA immunization.


Functional Vision Disorder.
Functional vision disorder (FVD) is a common problem seen in many neurologic and ophthalmologic practitioners' offices and may occur in isolation or in the presence of medical illness. This disorder presents with visual or oculomotor symptoms and manifests as vision loss in one or both eyes, visual field loss, double vision, oscillopsia, anisocoria, blepharospasm, or ptosis. Manual perimetry is the most effective method for determining functional visual loss, and the presence of a central scotoma in a functional visual field signifies that a neuropathophysiologic process is almost certainly present. The exact neuropathophysiologic mechanism of this disorder is unknown; however, information can be drawn from the small studies of FVD samples and studies examining neuropsychiatric factors in other conversion disorder semiologies. Psychological and psychiatric interventions can be useful in treating these patients.


Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis.
The nuclear factor-kappaB (NF-kappaB) pathway is a critical mediator of RANTES (regulated on activation, normal T cell expressed and secreted) gene regulation and therefore represents a potential target for therapy of endometriosis-associated symptoms. The objective of this study was to investigate the effects of the antiinflammatory drug sulindac on NF-kappaB activation, NF-kappaB-mediated gene expression, RANTES gene and protein expression in endometrial stromal cells isolated from women with endometriosis, and unaffected controls. This was a clinical experimental study. The study was conducted at a university hospital. The inflammatory response in endometriosis is augmented by a 5-fold increased TNFalpha-induced RANTES secretion from ectopic endometriotic stromal cells, compared with normal endometrial stromal cells (P < 0.05). Western blot analysis revealed basal activation of NF-kappaB in endometriotic cells, which could be suppressed by sulindac. EMSAs showed that sulindac dramatically decreased NF-kappaB activation and diminished TNFalpha and IL-1beta-induced NF-kappaB DNA binding activity. Sulindac pretreatment resulted in a significant decrease in TNFalpha-induced luciferase activity of NF-kappaB response element and -477 bp RANTES promoter constructs in normal and endometriotic stromal cells. The addition of sulindac to IL-1beta- and TNFalpha-treated endometriotic stromal cells also resulted in a 4-fold inhibition of RANTES protein secretion (P < 0.05). We have demonstrated that sulindac exerts strong antiinflammatory effects by suppression of NF-kappaB translocation, inhibition of NF-kappaB-mediated gene transcription, RANTES gene expression, and protein secretion in normal and endometriotic stromal cells. These results suggest that drugs targeting the NF-kappaB pathway may be beneficial in the treatment of endometriosis-associated symptoms.


Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress.
Carbon monoxide (CO), a reaction product of the cytoprotective heme oxygenase (HO)-1, is antiapoptotic in a variety of models of cellular injury, but the precise mechanisms remain to be established. In human umbilical vein endothelial cells, exogenous CO activated Nrf2 through the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK), resulting in HO-1 expression. CO-induced activation of PERK was followed by the phosphorylation of eukaryotic translation initiation factor 2alpha and the expression of activating transcription factor 4. However, CO fails to induce X-box binding protein-1 expression and activating transcription factor 6 cleavage. CO had no significant effect on synthesis of endoplasmic reticulum (ER) chaperone proteins such as the 78-kDa glucose-regulated proteins 78 and 94. Instead, CO prevented X-box binding protein 1 expression and activating transcription factor 6 cleavage induced by ER-stress inducers such as thapsigargin, tunicamycin and homocysteine. CO also prevented endothelial apoptosis triggered by these ER inducers through suppression of C/EBP homologous protein expression, which was associated with its activation of p38 mitogen-activated protein kinase. Similarly, endogenous CO produced from endothelial HO-1 induced by either exogenous CO or a pharmacological inducer was also cytoprotective against ER stress through C/EBP homologous protein suppression. Our findings suggest that CO renders endothelial cells resistant to ER stress not only by downregulating C/EBP homologous protein expression via p38 mitogen-activated protein kinase activation but also by upregulating Nrf2-dependent HO-1 expression via PERK activation. Thus, the HO-1/CO system might be potential therapeutics in vascular diseases associated with ER stress.


Network synchronizability analysis: a graph-theoretic approach.
This paper addresses the fundamental problem of complex network synchronizability from a graph-theoretic approach. First, the existing results are briefly reviewed. Then, the relationships between the network synchronizability and network structural parameters (e.g., average distance, degree distribution, and node betweenness centrality) are discussed. The effects of the complementary graph of a given network and some graph operations on the network synchronizability are discussed. A basic theory based on subgraphs and complementary graphs for estimating the network synchronizability is established. Several examples are given to show that adding new edges to a network can either increase or decrease the network synchronizability. To that end, some new results on the estimations of the synchronizability of coalescences are reported. Moreover, a necessary and sufficient condition for a network and its complementary network to have the same synchronizability is derived. Finally, some examples on Chua circuit networks are presented for illustration.


Using Social Marketing to Reduce Salt Intake in Iran.
Objectives: WHO has recommended that the average salt intake must be <5 grams per day. However, people consume salt much more in many countries. In this study, we design and implement an intervention based on social marketing model to reduce salt consumption in Yasuj, Iran. Materials and Methods: This study employed a quasi-experimental pretest-posttest with control group design which consisted of a formative research (qualitative-quantitative) and an interventional phase. To collect the qualitative data, six focus group discussions by participating of 66 people were established. The qualitative data were analyzed manually using directed content analysis. In quantitative study, 166 people aged 25-50 years completed a KAP questionnaire, and their average salt intake was determined through measuring sodium in their urine sample. By analyzing the data, marketing mix components were determined for designing an intervention. An educational package (including posters for installing in the kitchen, pamphlets, phone counseling, four educational classes, and brief interventions done by physicians and other health personnel) focused on reducing salt intake and using alternatives was developed. For one month, program was implemented for intervention group. Two months later, KAP survey and measuring the urine sodium were repeated for intervention and control groups. The data was compared for two groups, before and after the intervention by using independent t-test, paired t-tests and repeated measures ANOVA. Results: The qualitative findings showed that most participants agreed that the salt intake was high in Iran. Most of them recommended home-based and family-driven strategies to reduce salt intake, offered using healthier alternatives for salt, and recognized physicians and health care providers in healthcare facilities as the most important to encourage people to reduce salt intake. After the intervention, the mean and standard deviation of KAP were improved significantly in intervention group. The mean salt intake decreased significantly by 3.01 ± 2.38 in the intervention group and repeated measures ANOVA showed significant change over time (P < 0.001) and a significant difference between two groups (P = 0.04). Also, the interaction between time and group was significant (P = 0.001). Conclusion: The mean salt intake among the study population was approximately three times more than the level recommended by the WHO. The social marketing-based intervention succeeded in reducing the salt intake of the study subjects by ~3 grams on average.


Detonation nanodiamond: an organic platform for the suzuki coupling of organic molecules.
Detonation nanodiamond possesses facile surface functional groups and can be chemically processed for many engineering applications. In this work, we demonstrate the functionalization of nanoscale diamond particles with aryl organics using Suzuki coupling reactions. In route one, hydrogenated nanodiamond is derivatized with aryl diazonium to form the bromophenyl-nanodiamond complex, this is subsequently reacted with phenyl boronic acid to generate the biphenyl adduct. In route two, the nanodiamond is first derivatized with boronic acid groups to form the boronic acid-nanodiamond complex, this is followed by Suzuki cross coupling with arenediazonium tetrafluroborate salts to generate the biphenyl product. Good chemoselectivity can be obtained in both routes. The efficiencies of the Suzuki coupling reaction can be further improved by performing the chemistry in a microreactor where electro-osmotic flow accelerates the mixing of reactants. Using the Suzuki coupling reactions, we can functionalize nanodiamond with trifluoroaryls and increase the solubilities of nanodiamond in ethanol and hexane. Fluorescent nanodiamond can be generated by the Suzuki coupling of pyrene to nanodiamond.


Molecular memory with downstream logic processing exemplified by switchable and self-indicating guest capture and release.
Molecular-logic based computation (MLBC) has grown by accumulating many examples of combinational logic gates and a few sequential variants. In spite of many inspirations being available in biology, there are virtually no examples of MLBC in chemistry where sequential and combinational operations are integrated. Here we report a simple alcohol-ketone redox interconversion which switches a macrocycle between a large or small cavity, with erect aromatic walls which create a deep hydrophobic space or with collapsed walls respectively. Small aromatic guests can be captured or released in an all or none manner upon chemical command. During capture, the fluorescence of the alcohol macrocycle is quenched via fluorescent photoinduced electron transfer switching, meaning that its occupancy state is self-indicated. This represents a chemically-driven RS Flip-Flop, one of whose outputs is fed into an INHIBIT gate. Processing of outputs from memory stores is seen in the injection of packaged neurotransmitters into synaptic clefts for onward neural signalling. Overall, capture-release phenomena from discrete supermolecules now have a Boolean basis.


Co-expression of protein complexes in prokaryotic and eukaryotic hosts: experimental procedures, database tracking and case studies.
Structure determination and functional characterization of macromolecular complexes requires the purification of the different subunits in large quantities and their assembly into a functional entity. Although isolation and structure determination of endogenous complexes has been reported, much progress has to be made to make this technology easily accessible. Co-expression of subunits within hosts such as Escherichia coli and insect cells has become more and more amenable, even at the level of high-throughput projects. As part of SPINE (Structural Proteomics In Europe), several laboratories have investigated the use co-expression techniques for their projects, trying to extend from the common binary expression to the more complicated multi-expression systems. A new system for multi-expression in E. coli and a database system dedicated to handle co-expression data are described. Results are also reported from various case studies investigating different methods for performing co-expression in E. coli and insect cells.


Paliperidone Induced Hypoglycemia by Increasing Insulin Secretion.
We report the case of a 41-year-old woman with schizophrenia who developed persistent hypoglycemia following paliperidone administration. After discontinuing paliperidone, the hypoglycemia resolved, but symptoms of diabetes emerged. Therefore, it appears that the hypoglycemia induced by paliperidone may mask symptoms of diabetes. Paliperidone may induce hypoglycemia by increasing insulin secretion. This report could help elucidate the relationship between atypical antipsychotics and glucose metabolism.


Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating Oxidative Stress and Inflammation.
In clinic, excessive acetaminophen (APAP) can cause kidney damage with uncertain mechanisms. Recently, accumulating evidence demonstrated a pathogenic role of mitochondrial dysfunction in the kidney injury. Thus, in this study, rotenone, a mitochondrial complex I inhibitor, was applied to the mice with APAP-induced acute kidney injury to evaluate the effect of mitochondrial complex I inhibition on APAP nephrotoxicity. After 3 days of rotenone pretreatment, mice were administered with APAP (300mg/kg) by intraperitoneal injection for 24 h. Then the kidney injury, inflammation, and oxidative stress were evaluated. APAP significantly enhanced the BUN, serum creatine, and cystatin C levels in line with a moderate alteration of renal morphology. Strikingly, rotenone treatment normalized BUN, serum creatinine, and cystatin C levels, as well as the kidney morphology. Meanwhile, APAP enhanced tubular injury markers of NGAL and KIM-1 by 347- and 5-fold at mRNA levels, respectively. By Western blotting, we confirmed a 15-fold increment of NGAL in APAP-exposed kidneys. Importantly, rotenone treatment largely normalized NGAL and KIM-1 levels and attenuated inflammatory response in APAP-treated mice. Similarly, rotenone treatment enhanced the expressions of SOD1-3 compared with APAP group in line with a significant suppression of kidney MDA content. Finally, we observed that inhibition of mitochondrial complex III failed to protect against APAP-induced nephrotoxicity. Mitochondrial complex I inhibitor rotenone protected kidneys against APAP-induced injury possibly via the inhibition of mitochondrial oxidative stress and inflammation.


DTI-based upper limit of voxel free water fraction.
Free water (FW) in neuroimaging is non-flowing extracellular water in the cranium and brain tissue, and includes both cerebral spinal fluid (CSF) and fluid in intercellular space or edema. For a region such as a voxel (spatial unit of measurement in neuroimaging), the FW fraction is defined as the volume fraction of FW within that volume. Quantifying the FW fraction allows estimating contamination by fluid of neuroimaging or magnetic resonance spectroscopy measurements within a voxel. An upper limit to the fraction of FW within a voxel, based on any diffusion tensor imaging (DTI) sequence including a standard single shell at one b-value, can be derived from the standard diffusion tensor by scaling the third eigenvalue of the diffusion tensor. Assuming a two-compartment model, the diffusivity of a voxel is a combination of tissue and FW diffusivity. FW fraction is FW volume divided by voxel volume. Assuming FW diffuses equally in all directions, the diffusivity component is representable by a single, non-tensor diffusivity value. Since the diffusivity of water is known for a given temperature, and brain temperature is relatively constant, the FW diffusivity value can be assumed constant. The third eigenvector of the voxel diffusion tensor is the direction of least diffusivity and since the FW component of diffusivity is equal in all directions, we show that FW diffusivity cannot be lower than the third eigenvalue. Assuming FW contributes proportionally to voxel diffusivity, we show that the third eigenvalue divided by water diffusivity (as a constant based on known water diffusivity at 36.7 °C) forms an upper limit on the FW-fraction (fUL ). We calculated fUL for 384 subjects from the IXI dataset. Values mostly ranged from 0.1 to 0.6, and were closely related to radial diffusivity.Comparison with Existing Methods:fUL is easily calculated from any DTI data, but is not a true estimate of FW-fraction. The fUL measure offers a starting point in calculating the true FW-fraction of a voxel, or an easy-to-calculate voxel characteristic.


CD14(+) macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide.
Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman's correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn's post-test and the Mann-Whitney U tests. None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-α and IL-1β with CD68(+) cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14(+) macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14(+) cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS. Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.


Arterial blood carbonic Acid inversely determines lactic and organic acids.
To establish that arterial blood carbonic acid varies inversely with lactic acid in accordance with bicarbonate exchanging for lactate across cell membranes through the anion exchange mechanism to maintain the Gibbs-Donnan equilibrium. Over 5 years, lactate was measured on all blood gases taken from neonatal admissions, as well as organic acid whenever electrolytes were required. Arterial blood gases from 63 infants given high calcium TPN were analyzed. Twenty two needed continuous positive airways pressure (CPAP) only and 31 intermittent positive pressure ventilation (IPPV) and surfactant followed by CPAP to treat respiratory distress syndrome in 51 and meconium aspiration syndrome in 2. All survived and were free of infection. Excluded gases were those with high and falling lactate soon after delivery representing perinatal asphyxia, and those on dexamethasone. Strong inverse relations between carbonic and lactic acids were found at all gestational ages and, independent of glomerular filtration, between carbonic and organic acids. Lactate (mmol/L) = 62.53 X PCO2 (-0.96)(mmHg) r(2) 0.315, n 1232, p <0.001. Sixty divided by PCO2 is a convenient measure of physiological lactate at any given PCO2. In the first week, 9.13 ± 2.57% of arterial gases from infants on IPPV had lactates above 120/PCO2, significantly more than 4.74 ± 2.73% on CPAP (p<0.05) and 2.47 ± 2.39% on no support. Changes in arterial blood carbonic acid cause immediate inverse changes in lactic acid, because their anions interchange across cell membranes according to the Gibbs -Donnan equilibrium. Increasing PCO2 from 40 to 120 mmHg decreased lactate from 1.5 mmol/L to 0.5 mmol/L, so that the sum of carbonic and lactic acids increased from 2.72 mmol/L to only 4.17 mmol/L. This helps explain the neuroprotective effect of hypercapnoea and highlights the importance of avoiding any degree of hypocapnoea in infants on IPPV.


THE DILATABLE RING CANALS OF THE OVARIAN CYSTOCYTES OF HABROBRACON JUGLANDIS.
The canals connecting the ovarian cystocytes of Habrobracon juglandis are enclosed by a ring made up of eight leaves. Each leaf is composed of a monolayer of between and 70 short parallel microtubules which may be derived from the mid-body. The sliding of certain leaves past one another allows the ring to dilate as the cystocyte grows.


Identification of regions within the F domain of the human estrogen receptor alpha that are important for modulating transactivation and protein-protein interactions.
The estrogen receptor (ER)alpha is a biologically and clinically important ligand-modulated transcription factor. The F domain of the ERalpha modulates its functions in a ligand-, promoter-, and cell-specific manner. To identify the region(s) responsible for these functions, we characterized the effects of serial truncations within the F domain. We found that truncating the last 16 residues of the F domain altered the activity of the human ERalpha (hERalpha) on an estrogen response element-driven promoter in response to estradiol or 4-hydroxytamoxifen (4-OHT), its sensitivity to overexpression of the coactivator steroid receptor coactivator-1 in mammalian cells, and its interaction with a receptor-interacting domain of the coactivator steroid receptor coactivator-1 or engineered proteins ("monobodies") that specifically bind to ERalpha/ligand complexes in a yeast two-hybrid system. Most importantly, the ability of the ER to induce pS2 was reduced in MDA-MB-231 cells stably expressing this truncated ER vs. the wild-type ER. The region includes a distinctive segment (residues 579-584; LQKYYIT) having a high content of bulky and/or hydrophobic amino acids that was previously predicted to adopt a beta-strand-like structure. As previously reported, removal of the entire F domain was necessary to eliminate the agonist activity of 4-OHT. In addition, mutation of the vicinal glycine residues between the ligand-binding domain and F domains specifically reduced the 4-OHT-dependent interactions of the hERalpha ligand-binding domain and F domains with monobodies. These results show that regions within the F domain of the hERalpha selectively modulate its activity and its interactions with other proteins.


Particle size and aggregation effects on magnetite reactivity toward carbon tetrachloride.
Nanoparticulate magnetite is found in many natural and engineered environments. This study characterized the reactivity of this material toward carbon tetrachloride (CCl4). Particle diameter plays an important role, with nominal (9 nm) magnetite suspensions exhibiting greater reactivity on both mass (k(m)) and surface area normalized (k(SA)) bases than (80 nm) magnetite suspensions. For the (9 nm) suspension, the aggregation state of the particles affects the measured km values. At 0.001 M ionic strength and pH 7, k(m) (=0.052-0.139 L g(-1) h(-1)) was as much as seven times larger than at 1 M (k(m) = 0.025-0.030 L g(-1) h(-1)). This decrease in reactivity with an increase in ionic strength is related to the measured diameter of the aggregates present in solution, thus implicating aggregate size as an important variable. This work is the first to indicate that both particle size and aggregation state must be considered when evaluating the reactivity of nanoparticle suspensions with groundwater contaminants.


Pay for performance promoted in California.
The California-based Integrative Healthcare Association (IHA), a collaborative group made up of health plans, physician groups, employers, consumers, and health care systems, last month unveiled a new initiative--called Pay for Performance--that would base physician payments on providing quality care each year and would give consumers comparative data on physician groups.


Long-term effect of catheter ablation on tachycardia-bradycardia syndrome: evidenced by 10 years follow up.
Background: Catheter ablation has been used for the treatment of tachycardia-bradycardia syndrome (TBS). However, data on its long-term effect of rhythm control and stroke are limited.Method and results: Patients with TBS admitted in the First Affiliated Hospital of Dalian Medical University from 2002 to 2013 were reviewed in the present study. A total of 150 patients were enrolled. Seventy-nine patients underwent catheter ablation (CA group) and 71 patients chose implantation of pacemaker (PM group). The two groups were followed up for 123.01 ± 29.68 and 120.67 ± 31.05 months respectively. The CA group underwent 1.2 ± 0.5 procedure. Of the CA group, 70.9% patients exhibited sinus rhythm without long pauses or the need of anti-arrhythmia drugs (AADs). In contrast, no patient in the PM group was free of atrial fibrillation (AF). A higher proportion in the PM group progressed to persistent AF than in that in the CA group (9.9% vs. 1.3%, p < .05). The incidence of new-onset stroke in the PM group was significantly higher than that in the CA group (15.4% vs. 5.1%, p < .05).Conclusions: Even for long-term following up, catheter ablation is effective for preventing both the tachycardia and bradycardia components for the majority of patients with TBS without the need for further pacemaker implantation. Furthermore, ablation can reduce the stroke incidence of TBS through eliminating AF and reducing the progression to persistent AF.


Mortality after orthotopic liver transplantation. An analysis of the causes of death in the first 50 liver transplantations in Groningen, The Netherlands.
An analysis was made of the causes of death in 22 of 50 patients receiving consecutive orthotopic liver transplants. A close look at the fatal course of these patients revealed three major patterns: surgical complications (27%), pathology of the hepatic artery anastomosis (23%), and cholestasis (32%). Technical factors were the major reasons for excessive peroperative blood loss, and not the coagulopathy accompanying the liver disease. The etiology of hepatic artery thrombosis is not known. It leads to irreversible damage of the graft, causing death due to acute hepatic failure or to cholangitis and sepsis. The only way to treat patients with this complication is retransplantation. Several factors can induce cholestasis. Retrospectively, it appears that this was mostly due to inappropriate immunosuppression, often a result of the difficult differential diagnosis between rejection and viral infection. Recognition of these three basic patterns should enable us to anticipate their subsequent complications. This may lead to a reduction in morbidity and mortality after liver transplantation.


Cross-modal phonetic encoding facilitates the McGurk illusion and phonemic restoration.
In spoken language, audiovisual (AV) perception occurs when the visual modality influences encoding of acoustic features (e.g., phonetic representations) at the auditory cortex. We examined how visual speech (mouth movements) transforms phonetic representations, indexed by changes to the N1 auditory evoked potential (AEP). EEG was acquired while human subjects watched and listened to videos of a speaker uttering consonant vowel (CV) syllables, /ba/ and /wa/, presented in auditory-only or AV congruent or incongruent contexts or in a context in which the consonants were replaced by white noise (noise replaced). Subjects reported whether they heard "ba" or "wa." We hypothesized that the auditory N1 amplitude during illusory perception (caused by incongruent AV input, as in the McGurk illusion, or white noise-replaced consonants in CV utterances) should shift to reflect the auditory N1 characteristics of the phonemes conveyed visually (by mouth movements) as opposed to acoustically. Indeed, the N1 AEP became larger and occurred earlier when listeners experienced illusory "ba" (video /ba/, audio /wa/, heard as "ba") and vice versa when they experienced illusory "wa" (video /wa/, audio /ba/, heard as "wa"), mirroring the N1 AEP characteristics for /ba/ and /wa/ observed in natural acoustic situations (e.g., auditory-only setting). This visually mediated N1 behavior was also observed for noise-replaced CVs. Taken together, the findings suggest that information relayed by the visual modality modifies phonetic representations at the auditory cortex and that similar neural mechanisms support the McGurk illusion and visually mediated phonemic restoration. NEW & NOTEWORTHY Using a variant of the McGurk illusion experimental design (using the syllables /ba/ and /wa/), we demonstrate that lipreading influences phonetic encoding at the auditory cortex. We show that the N1 auditory evoked potential morphology shifts to resemble the N1 morphology of the syllable conveyed visually. We also show similar N1 shifts when the consonants are replaced by white noise, suggesting that the McGurk illusion and the visually mediated phonemic restoration rely on common mechanisms.


[Therapy of chronic hepatitis B].
The aim of chronic hepatitis B therapy is to suppress hepatitis B virus replication, to control disease activity and progression towards cirrhosis. The first-line drug is the pegylated interferon a, which suppresses HBV replication in 40% of cases, albeit burdened with several contraindications and side effects. Lamivudine, a nucleoside analog inhibiting HBV reverse transcriptase, is indicated in case of failure or contraindication to interferon, may however lead to the selection of resistant mutant HBV strains (20% yearly). In that case, adefovir is indicated and has a lower risk of selection of resistant strains (5% yearly). More effective drugs (telbivudine and entecavir) will soon be available in Switzerland. Two inhibitors of HIV (tenofovir and emtricitabine) may also be used to treat hepatitis B in selected cases. Drug combinations, although supported by theoretical considerations, bring no known clinical benefit and are not reimbursed.


[A survey of drug utilization in psychiatric hospitals in Japan: the basic analysis of the current status of prescription patterns].
Although concern about the prescription pattern of psychotropics is growing, there have been very few surveys in Japan. In this survey conducted in 1993, prescription data, patient characteristics, etc. were collected for 2,395 inpatients from 18 psychiatric hospitals. Their mean age was 48.4 (S.D. = 13.6). Of these patients, 1,818 (75.9%) were diagnosed with schizophrenia, 115 (4.8%) with mood disorder, and 102 (4.3%) with mental retardation. The results were as follows. 1) They were prescribed an average of 10.1 different drugs: of these, 5.6 were various psychotropics (2.6 neuroleptics, 1.2 antiparkinsonian drugs, 1.0 hypnotics). 2) The mean daily dose of antipsychotics was 1,082 mg of chlorpromazine equivalent. 3) The most commonly prescribed neuroleptic was haloperidol (53.2% of the total patients) followed by levomepromazine (48.7%), chlorpromazine (24.8%), bromperidol (18.7%), and zotepine (18.3%).


Intraoperative fluoroscopic safety assessment of femoral head implants with 3-dimensional risk parameters to minimize cut-out.
This study aimed to introduce a method to extract the 3-dimensional spatial position of the femoral head implant from 2-dimensional fluoroscopic projections, allowing surgeons to assess fixation much more accurately and prevent cut-out complications in proximal femoral nailing. To define a safety region for the tip in the femoral head, a novel 3-dimensional distance-based risk parameter called TSD3D was introduced. An intersection algorithm was developed that solely takes the fluoroscopic anteroposterior and lateral distances to reveal the 3-dimensional location of the screw or Kirschner wire tip, enabling the utilization of the 3-dimensional parameter. Orthogonal per- spectives of 6 femur proximal bone substitutes with randomly inserted Kirschner wires were imaged under fluoroscopy. The developed algorithm was used to calculate the implant tip location in 3-dimensional from 2-dimensional images for each case. Algorithm accuracy was validated with the computed tomography-obtained 3-dimensional models of the same femur substitutes. The newly introduced risk parameter successfully visualizes 3-dimensional safety regions. Utilizing the 2-dimensional fluoro- scopic distances as inputs to the algorithm, the 3-dimensional position of the implanted Kirschner wire tip is calculated with a maximum of 9.8% error for a single Cartesian-coordinate measurement comparison. By incorporating the newly introduced 3-dimensional risk parameter, surgeons can more precisely evaluate the position of the implant and avoid cut-out complications, instead of relying solely on misleading 2-dimensional fluoroscopic projections of the femoral head.


Xenon Tetrafluoride: Fluorine-19 High-Resolution Magnetic Resonance Spectrum.
The F(19) spectrum of XeF(4) dissolved in anhydrous hydrogen fluoride has been observed at two frequencies, yielding a F(19) chemical shift of 175 parts per million to lower field than the solvent and a Xe(129)-F(19) spin-spin coupling constant, confirmed by double irradiation, of 3860 cycles per second. Absence of fast F(19) chemical exchange and collapse of the Xe(131)-F(19) coupling by quadrupole relaxation may be inferred from the spectrum.


Development of Fc-Fused Cocaine Hydrolase for Cocaine Addiction Treatment: Catalytic and Pharmacokinetic Properties.
Cocaine abuse is a worldwide public health and social problem without a US Food and Drug Administration (FDA)-approved medication. Accelerating cocaine metabolism that produces biologically inactive metabolites by administration of an efficient cocaine hydrolase (CocH) has been recognized as a promising strategy for cocaine abuse treatment. However, the therapeutic effects of CocH are limited by its short biological half-life (e.g., 8 h or shorter in rats). In this study, we designed and prepared a set of Fc-fusion proteins constructed by fusing Fc(M3) with CocH3 at the N-terminus of CocH3. A linker between the two protein domains was optimized to improve both the biological half-life and catalytic activity against cocaine. It has been concluded that Fc(M3)-G6S-CocH3 not only has fully retained the catalytic efficiency of CocH3 against cocaine but also has the longest biological half-life (e.g., ∼ 136 h in rats) among all of the long-acting CocHs identified so far. A single dose (0.2 mg/kg, IV) of Fc(M3)-G6S-CocH3 was able to significantly attenuate 15 mg/kg cocaine-induced hyperactivity for at least 11 days (268 h) after the Fc(M3)-G6S-CocH3 administration.


Myxoid dermatofibrosarcoma protuberans: clinicopathologic, immunohistochemical, and molecular analysis of eight cases.
Dermatofibrosarcoma protuberans (DFSP) represents a locally aggressive mesenchymal neoplasm of skin and subcutis with characteristic clinicopathologic, immunohistochemical, and molecular findings. In addition to typical cases, morphologic variants such as pigmented, fibrosarcomatous, myofibroblastic, and granular cell DFSP have been described. Purely or predominantly myxoid DFSP is extremely rare, and may cause considerable diagnostic problems. Eight cases of predominantly myxoid DFSP were studied. Paraffin-embedded blocks and slides were retrieved from the files of the authors. Clinical data were obtained from the referring pathologists and dermatologists. Immunohistochemistry was performed using the ABC method, and three cases were studied by polymerase chain reaction technique. There were six male and two female patients (age range: 29 to 74 years). Locations included the inguinal area (three cases), thigh, upper arm, shoulder, abdominal wall, and back (one each). The patients were treated by wide excision as well as reexcision. Tumor size ranged from 1.5 to 12 cm. Histologically, a nodular growth with peripheral diffuse infiltration, as well as a diffusely infiltrating growth of relatively uniform spindled and stellated tumor cells containing slightly enlarged nuclei, was noted. Three cases were entirely myxoid, and in five cases more than 80% of the tumor area showed myxoid stromal changes. In two cases each, focal fibrosarcomatous and focal giant cell fibroblastoma-like changes were present. At least focally, hypocellular areas were evident in one case. Scattered enlarged tumor cells were seen in two cases. The mitotic rate ranged from 1 to 10 mitoses in 10 high-power fields. Numerous blood vessels with slightly fibrosed vessel walls were seen in seven cases. Immunohistochemically, tumor cells in all cases stained positively for CD34, and in one case each a focal expression of alpha-smooth muscle actin and epithelial membrane antigen (EMA) was noted. The remaining antibodies (CD99, CD31, S-100, Factor XIIIa) were all negative. Polymerase chain reaction technique showed in one case the characteristic COL1A1-PDGFB fusion gene. Follow-up information in seven cases (range: 2 months to 10 years; mean: 62 months; median: 48 months) revealed a local recurrence at 5 years. In conclusion, myxoid DFSP represents a very rare morphologic variant with characteristic changes that has to be distinguished from benign and malignant myxoid mesenchymal neoplasms as superficial angiomyxoma, superficial acral fibromyxoma, myxoid solitary fibrous tumor, myxoid perineurioma, low-grade myxofibrosarcoma, low-grade fibromyxoid sarcoma, myxoid liposarcoma, and myxoid synovial sarcoma.