Endovascular treatment of 170 consecutive cranial dural arteriovenous fistulae: results and complications.
This study aims to evaluate a single-center experience with endovascular treatment of cranial dural arterievenous fistulae (CDAVF). The clinical and radiological records of 170 consecutive patients harboring a CDAVF and treated endovascularly in a 16-year period were reviewed. A variety of data related to demographics, features of the lesion, treatment, outcome, and follow-up were analyzed with emphasis to the results and complications. Half of the lesions had cortical venous drainage (CVD) in the initial angiographic investigation, whereas 26 % had exclusively CVD. Sixty-seven percent of our patients presented with benign symptoms and 33 % with aggressive symptoms. In 60.5 % of the patients with benign lesion (without CVD), an anatomic cure in the immediate postinterventional angiogram without complication or permanent morbidity was achieved, whereas 69 % of the patients with aggressive lesions (with CVD) had an anatomic cure in the postinterventional final angiogram with all permanent-morbidity cases belonging to this group. The average of endovascular operation sessions per patient was 1.2. In a mean follow-up period of 2.8 years, the overall complete occlusion rate was 85.5 % (78 % for the benign group and 89.5 % for the aggressive group) and clinical cure and/or improvement rate of 93 %. The operative mortality was zero, and permanent neurologic morbidity was 2.3 %. In 73 % of our cases, N-butyl cyanoacrylate (NBCA) was used as the only or main embolic material. Endovascular embolization is the treatment of choice for CDAVF. High rates of good anatomical and clinical results, associated with very low operative complication rate can be achieved with few embolization sessions. Although mastering of a permanent embolic material is important, the therapeutic strategy should be individulized and not material based.


A population genomic scan in Chorthippus grasshoppers unveils previously unknown phenotypic divergence.
Understanding the genetics of speciation and the processes that drive it is a central goal of evolutionary biology. Grasshoppers of the Chorthippus species group differ strongly in calling song (and corresponding female preferences) but are exceedingly similar in other characteristics such as morphology. Here, we performed a population genomic scan on three Chorthippus species (Chorthippus biguttulus, C. mollis and C. brunneus) to gain insight into the genes and processes involved in divergence and speciation in this group. Using an RNA-seq approach, we examined functional variation between the species by calling SNPs for each of the three species pairs and using FST -based approaches to identify outliers. We found approximately 1% of SNPs in each comparison to be outliers. Between 37% and 40% of these outliers were nonsynonymous SNPs (as opposed to a global level of 17%) indicating that we recovered loci under selection. Among the outliers were several genes that may be involved in song production and hearing as well as genes involved in other traits such as food preferences and metabolism. Differences in food preferences between species were confirmed with a behavioural experiment. This indicates that multiple phenotypic differences implicating multiple evolutionary processes (sexual selection and natural selection) are present between the species.


Insurance Status and Continuity for Young Adults With First-Episode Psychosis.
Insurance status and continuity may affect access to and quality of care. The authors characterized patterns of and changes in insurance status over 1 year among people with first-episode psychosis (FEP), comparing insurance patterns with adults of similar age in the general population. Longitudinal data on insurance status and predictors of insurance status among adults with FEP were obtained from RAISE-ETP (Recovery After an Initial Schizophrenia Episode-Early Treatment Program) study participants with complete 1-year data (N=288). The frequencies of insurance status and transitions are presented. Bivariate comparisons were used to assess the impact of the comprehensive coordinated care intervention in RAISE-ETP on insurance changes. These data were compared with contemporaneous longitudinal data in the 2011 Medical Expenditures Panel Study. The RAISE-ETP experimental intervention did not significantly change insurance status. At baseline, levels of uninsurance (47%) and public insurance (31%) were higher among RAISE-ETP participants than among a similar age group in the general public (29% and 13%, respectively). Insurance transitions were common among people with FEP, although 79% of those with public insurance at baseline also had public insurance at 1 year. Of studied RAISE-ETP participants, 60% had a period of uninsurance during the year studied. Compared with a national sample, people with FEP were more likely to use public insurance but still had high persistence of 12-month uninsurance. That over half of the RAISE-ETP participants had a period of uninsurance suggests that more research is needed on whether these periods affect treatment continuity and medication adherence.


Developmental problems in patients with oesophageal atresia: a longitudinal follow-up study.
To longitudinally evaluate motor development and predictive factors in school-age children with oesophageal atresia. Cohort study with prospective longitudinal follow-up. Outpatient clinic of a tertiary university paediatric hospital. Children with oesophageal atresia born between January 1999 and May 2006 were assessed at 5 and 8 years of age. None. Motor performance was evaluated at 5 and 8 years using the Movement Assessment Battery for Children (M-ABC). Additionally, we evaluated perinatal characteristics, duration of anaesthesia within the first 24 months, socioeconomic status, sports participation and school performance at time of follow-up and intelligence and sustained attention at the age of 8 years. In 5-year-olds (n=54), the mean (SD) z-score M-ABC was slightly, but significantly lower than age-predicted normative values (-0.75 (0.83), p<0.001). In 8-year-olds (n=49), the z-score M-ABC was -0.53 (0.91) (p<0.001), intelligence was normal, but sustained attention was impaired: z-score speed (-1.50 (1.73)) and raw score attentional fluctuation (3.99 (1.90)) (both p<0.001). Motor problems mainly concerned gross motor performance. Duration of anaesthesia and sustained attention were negatively associated with motor development; sports participation was positively associated. Longer duration of anaesthesia and sustained attention problems were associated with gross motor problems in school-age patients with oesophageal atresia. Parental awareness of risks for motor problems may provide the opportunity to offer timely intervention.


Short-term vitamin E treatment impairs reactive oxygen species signaling required for adipose tissue expansion, resulting in fatty liver and insulin resistance in obese mice.
The use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity. C57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group) or without (O group) vitamin E supplementation. O mice developed a mild degree of obesity, which was not enough to induce metabolic alterations or oxidative stress. These animals exhibited a healthy expansion of retroperitoneal white adipose tissue (rpWAT) and the liver showed no signs of lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice were insulin resistant. In the rpWAT they presented a reduced generation of ROS, even below physiological levels (C: 1651.0 ± 212.0; O: 3113 ± 284.7; OE: 917.6 ±104.4 RFU/mg protein. C vs OE p< 0.01). ROS decay may impair their action as second messengers, which could account for the reduced adipocyte differentiation, lipid transport and adipogenesis compared to the O group. Together, these processes limited the expansion of this fat pad and as a consequence, lipid flux shifted towards the liver, causing steatosis and hepatomegaly, which may contribute to the marked insulin resistance. This study provides in vivo evidence for the role of ROS as second messengers in adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation below physiological levels when the oxidative process has not yet been established may be the cause of the controversial results obtained by antioxidant therapy.


Regulation of brain gene expression in honey bees by brood pheromone.
Pheromones are very important in animal communication. To learn more about the molecular basis of pheromone action, we studied the effects of a potent honey bee pheromone on brain gene expression. Brood pheromone (BP) caused changes in the expression of hundreds of genes in the bee brain in a manner consistent with its known effects on behavioral maturation. Brood pheromone exposure in young bees causes a delay in the transition from working in the hive to foraging, and we found that BP treatment tended to upregulate genes in the brain that are upregulated in bees specialized on brood care but downregulate genes that are upregulated in foragers. However, the effects of BP were age dependent; this pattern was reversed when older bees were tested, consistent with the stimulation of foraging by BP in older bees already competent to forage. These results support the idea that one way that pheromones influence behavior is by orchestrating large-scale changes in brain gene expression. We also found evidence for a relationship between cis and BP regulation of brain gene expression, with several cis-regulatory motifs statistically overrepresented in the promoter regions of genes regulated by BP. Transcription factors that target a few of these motifs have already been implicated in the regulation of bee behavior. Together these results demonstrate strong connections between pheromone effects, behavior, and regulation of brain gene expression.


Determination of the dynamics of the odour release from a pig house, using an electronic odour sensor.
The widely fluctuating operating conditions in pig husbandry, due to climatic and biological changes (changes in temperature and air flowrate between day and night, as well as between summer and winter, increasing animal mass during the fattening process, etc.) exert a significant influence on the amount of actual odour emission. The project presented here comprised the measurement of seasonal (fattening course), daytime-related, and short-term (feeding) dynamic effects of odour release, as well as the identification of potential factors which influence the amount of odour emitted. In parallel with "classic" olfactometry, an electronic odour sensor with a chemosensor array of ten metal oxide sensors was employed. The highest odour emissions are measured on hot summer days, while the lowest emissions were determined on cold winter days. On the one hand, the sensor signals of the electronic odour sensor exhibited considerable differences on days with large volume flow alterations. On the other hand, continuous measurement with the electronic odour sensor allowed changes in the gas- and odorant composition of the exhaust air during feeding times to be shown. From the measurement results, recommendations for odour sampling, the consideration of seasonal odour emission fluctuations, and the use of electronic odour sensors for the evaluation of odour emissions have been derived.


MDCT in ischaemic colitis: how to define the aetiology and acute, subacute and chronic phase of damage in the emergency setting.
Ischemic colitis (IC) is the most common vascular disorder of the gastrointestinal tract with a reported incidence of 6.1-44 cases/100,000 person years with confirmatory histopathology. However, the true incidence of IC poses some difficulty, and even vigilant clinicians with patients at high risk often miss the diagnosis, since clinical presentation is non-specific or could have a mild transient nature. Detection of IC results is crucial to plan the correct therapeutic approach and reduce the reported mortality rate (4-12%). Diagnosis of IC is based on a combination of clinical suspicion, radiological, endoscopic and histological findings. Some consider colonoscopy as a diagnostic test of choice; however, preparation is required and it is not without risk, above all in patients who are severely ill. There are two manifestations of vascular colonic insult: ischaemic and reperfusive. The first one occurs above all during ischaemic/non-occlusive mesenteric ischaemia; in this case, the colonic wall appears thinned with dilated lumen and fluid appears in the paracolic space. When reperfusion occurs, the large bowel wall appears thickened and stratified, because of subepithelial oedema and/or haemorrhage, with consequent lumen calibre reduction. Shaggy contour of the involved intestine and misty mesentery are associated with the pericolic fluid. The pericolic fluid results are a crucial finding for IC diagnosis since its evidence suggests the presence of an ongoing damage thus focusing the attention on other pathological aspects which could be otherwise misdiagnosed, such as thinned or thickened colonic wall. Moreover, the pericolic fluid may increase or decrease, depending on the evolution of the ischaemic damage, suggesting the decision of medical or surgical treatment. Radiologists should not forget the hypothesis of IC, being aware that multidetector CT could be sufficient to suggest the diagnosis of IC, allowing for early identification and grading definition, and in a short-term follow-up, discriminating patients who need urgent surgery from patients in whom medical treatment and follow-up can be proposed.


The influence of types of character on processing background information in narrative discourse.
The background sentence The air was cold and clammy depicts setting information which may or may not be of significance to a given character in a narrative. We tested the hypothesis that such information is processed with respect to the main character in a narrative rather than with respect to a secondary character. In Experiment 1, subjects making attributions of awareness of such background states were more likely to attribute such awareness to main than to secondary characters. In Experiment 2, using self-paced reading, we showed that such information is more important for main than for secondary characters during reading. Thus, unattached background information is processed with respect to main characters. This bias provides a source of control over the processing necessary to establish a coherent representation during the reading of narratives. Experiment 3 eliminated the possibility that the effects were due to generally shallower processing of sentences centered on secondary characters.


[Transformation of the synaptic apparatus of the rabbit sensorimotor cortex following creation of a polarization dominant].
Ultrastructural transformations of axo-somatic and axo-dendritic synapses of the rabbit sensorimotor cortex were studied during: 1) polarization of the cortical surface with a DC anode and 2) the setting up of a polarization motor dominant. A comparison between the structural characteristics of the examined region of the cerebral cortex of the two groups of animals revealed transformations in the synaptic apparatus, which may be regarded as a result of the formation of a temporary connection: an increase in the number of axo-dendritic synapses with considerably thickened postsynaptic membranes; an increase in the number of axonic terminals with a concentration of synaptic vesicles and mitochondria content. The indicated changes were more pronounced in the deep layers of the sensorimotor cortex.


Intensiometric biosensors visualize the activity of multiple small GTPases in vivo.
Ras and Rho small GTPases are critical for numerous cellular processes including cell division, migration, and intercellular communication. Despite extensive efforts to visualize the spatiotemporal activity of these proteins, achieving the sensitivity and dynamic range necessary for in vivo application has been challenging. Here, we present highly sensitive intensiometric small GTPase biosensors visualizing the activity of multiple small GTPases in single cells in vivo. Red-shifted sensors combined with blue light-controllable optogenetic modules achieved simultaneous monitoring and manipulation of protein activities in a highly spatiotemporal manner. Our biosensors revealed spatial dynamics of Cdc42 and Ras activities upon structural plasticity of single dendritic spines, as well as a broad range of subcellular Ras activities in the brains of freely behaving mice. Thus, these intensiometric small GTPase sensors enable the spatiotemporal dissection of complex protein signaling networks in live animals.


Assembly of Six Types of Heteroleptic Pd2L4 Cages under Kinetic Control.
Heteroleptic assemblies composed of several kinds of building blocks have been seen in nature. It is still unclear how natural systems design and create such complicated assemblies selectively. Past efforts on multicomponent self-assembly of artificial metal-organic cages have mainly focused on finding a suitable combination of building blocks to lead to a single multicomponent self-assembly as the thermodynamically most stable product. Here, we present another approach to selectively produce multicomponent Pd(II)-based self-assemblies under kinetic control based on the selective ligand exchanges of weak Pd-L coordination bonds retaining the original orientation of the metal centers in a kinetically stabilized cyclic structure and on local reversibility given in certain areas of the energy landscape in the presence of the assist molecule that facilitates error correction of coordination bonds. The kinetic approach enabled us to build all six types of Pd2L4 cages and heteroleptic tetranuclear cages composed of three kinds of ditopic ligands. Although the cage complexes thus obtained are metastable, they are stable for 1 month or more at room temperature.


The beginnings of crop phosphoproteomics: exploring early warning systems of stress.
This review examines why a knowledge of plant protein phosphorylation events is important in devising strategies to protect crops from both biotic and abiotic stresses, and why proteomics should be included when studying stress pathways. Most of the achievements in elucidating phospho-signaling pathways in biotic and abiotic stress are reported from model systems: while these are discussed, this review attempts mainly to focus on work done with crops, with examples of achievements reported from rice, maize, wheat, grape, Brassica, tomato, and soy bean after cold acclimation, hormonal and oxidative hydrogen peroxide treatment, salt stress, mechanical wounding, or pathogen challenge. The challenges that remain to transfer this information into a format that can be used to protect crops against biotic and abiotic stresses are enormous. The tremendous increase in the speed and ease of DNA sequencing is poised to reveal the whole genomes of many crop species in the near future, which will facilitate phosphoproteomics and phosphogenomics research.


Satiation in cutaneous saltation.
The extent of cutaneous saltation (the illusory displacement of a tap presented to one skin locus by another tap occurring close in time at another locus) was modified by a "preconditioning" stimulus presented prior to and at a site distant from the saltatory test pattern. The 10-sec vibratory preconditioning (PC) stimulus appears to be analogous to inspection figures that "satiate" the perceptual field in experiments on figural aftereffects, producing changes in the perceived size, position, or shape of subsequent stimuli. The direction of displacement of the saltatory phantom was always away from the locus of the prior PC stimulus, consistent with results observed in studies of visual and kinesthetic aftereffects. Th- amount of repulsion and the rate at which the saltatory phantom returned to its initial position depend on the intensity, locus, and number of PC stimuli. As with figural aftereffects, these results resist explanation by peripheral mechanisms such as adaptation.


Photoacoustic imaging for guidance of interventions in cardiovascular medicine.
Imaging guidance is paramount to procedural success in minimally invasive interventions. Catheter-based therapies are the standard of care in the treatment of many cardiac disorders, including coronary artery disease, structural heart disease and electrophysiological conditions. Many of these diseases are caused by, or effect, a change in vasculature or cardiac tissue composition, which can potentially be detected by photoacoustic imaging. This review summarizes the state of the art in photoacoustic imaging approaches that have been proposed for intervention guidance in cardiovascular care. All of these techniques are currently in the preclinical phase. We will conclude with an outlook towards clinical applications.


Efficient Syntheses of Biobased Terephthalic Acid, p-Toluic Acid, and p-Methylacetophenone via One-Pot Catalytic Aerobic Oxidation of Monoterpene Derived Bio-p-cymene.
An efficient elevated-pressure catalytic oxidative process (2.5 mol % Co(NO3)2, 2.5 mol % MnBr2, air (30 bar), 125 °C, acetic acid, 6 h) has been developed to oxidize p-cymene into crystalline white terephthalic acid (TA) in ∼70% yield. Use of this mixed Co2+/Mn2+ catalytic system is key to obtaining high 70% yields of TA at relatively low reaction temperatures (125 °C) in short reaction times (6 h), which is likely to be due to the synergistic action of bromine and nitrate radicals in the oxidative process. Recycling studies have demonstrated that the mixed metal catalysts present in recovered mother liquors could be recycled three times in successive p-cymene oxidation reactions with no loss in catalytic activity or TA yield. Partial oxidation of p-cymene to give p-methylacetophenone (p-MA) in 55-60% yield can be achieved using a mixed CoBr2/Mn(OAc)2 catalytic system under 1 atm air for 24 h, while use of Co(NO3)2/MnBr2 under 1 atm O2 for 24 h gave p-toluic acid in 55-60% yield. Therefore, access to these simple catalytic aerobic conditions enables multiple biorenewable bulk terpene feedstocks (e.g., crude sulfate turpentine, turpentine, cineole, and limonene) to be converted into synthetically useful bio-p-MA, bio-p-toluic acid, and bio-TA (and hence bio-polyethylene terephthalate) as part of a terpene based biorefinery.


ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling.
Caenorhabditis elegans is a powerful model to study the molecular basis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is caused by mutations in the polycystic kidney disease (PKD)1 or PKD2 gene, encoding polycystin (PC)-1 or PC-2, respectively. The C. elegans polycystins LOV-1 and PKD-2 are required for male mating behaviors and are localized to sensory cilia. The function of the evolutionarily conserved polycystin/lipoxygenase/alpha-toxin (PLAT) domain found in all PC-1 family members remains an enigma. Here, we report that ATP-2, the beta subunit of the ATP synthase, physically associates with the LOV-1 PLAT domain and that this interaction is evolutionarily conserved. In addition to the expected mitochondria localization, ATP-2 and other ATP synthase components colocalize with LOV-1 and PKD-2 in cilia. Disrupting the function of the ATP synthase or overexpression of atp-2 results in a male mating behavior defect. We further show that atp-2, lov-1, and pkd-2 act in the same molecular pathway. We propose that the ciliary localized ATP synthase may play a previously unsuspected role in polycystin signaling.


Novel long-acting bronchodilators for COPD and asthma.
An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once-daily beta2-agonists or ultra long-acting beta2-agonists (LABAs) such as carmoterol, indacaterol, GSK-159797, GSK-597901, GSK-159802, GSK-642444 and GSK-678007 are under development for the treatment of asthma and COPD. Also some new long-acting antimuscarinic agents (LAMAs) such as aclidinium, LAS-35201, GSK656398, GSK233705, NVA-237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once-daily dual-action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M3 antagonist-beta2 agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products.


Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ.
Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110γ participates in these processes by sustaining β-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity via an unknown kinase-independent mechanism. We have discovered that p110γ anchors protein kinase A (PKA) through a site in its N-terminal region. Anchored PKA activates PDE3B to enhance cAMP degradation and phosphorylates p110γ to inhibit PIP(3) production. This provides local feedback control of PIP(3) and cAMP signaling events. In congestive heart failure, p110γ is upregulated and escapes PKA-mediated inhibition, contributing to a reduction in β-adrenergic receptor density. Pharmacological inhibition of p110γ normalizes β-adrenergic receptor density and improves contractility in failing hearts.


Glioblastoma Circulating Cells: Reality, Trap or Illusion?
Metastases are the hallmark of cancer. This event is in direct relationship with the ability of cancer cells to leave the tumor mass and travel long distances within the bloodstream and/or lymphatic vessels. Glioblastoma multiforme (GBM), the most frequent primary brain neoplasm, is mainly characterized by a dismal prognosis. The usual fatal issue for GBM patients is a consequence of local recurrence that is observed most of the time without any distant metastases. However, it has recently been documented that GBM cells could be isolated from the bloodstream in several studies. This observation raises the question of the possible involvement of glioblastoma-circulating cells in GBM deadly recurrence by a "homing metastasis" process. Therefore, we think it is important to review the already known molecular mechanisms underlying circulating tumor cells (CTC) specific properties, emphasizing their epithelial to mesenchymal transition (EMT) abilities and their possible involvement in tumor initiation. The idea is here to review these mechanisms and speculate on how relevant they could be applied in the forthcoming battles against GBM.


Continuous ST-segment monitoring associated with infarct size and left ventricular function in the GUSTO-I trial.
The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of alpha-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST-trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy.


An enzyme-linked immunosorbent assay for the detection of esfenvalerate metabolites in human urine.
The pyrethroids are one of the most heavily used insecticide classes in the world. Sensitive and rapid analytical techniques are needed for assessments of human exposure to these compounds. Highly sensitive and selective ELISAs for glycine conjugates of esfenvalerate key metabolites phenoxybenzoic acid (PBA) and s-fenvalerate acid (sFA) were developed. Rabbits were immunized with either N-(3-phenoxybenzoyl)-4-amino-L-phenylalanine-fetuin or N-[(S)-4-chloro-2-(methylethyl)benzeneacetyl]-4-amino-L-phenyla lan ine -fetuin, and all sera were screened against numerous coating antigens. The antibodies with the least interference and best sensitivity were optimized and characterized. The I(50)s for sFA-glycine and PBA-glycine in buffer were found to be 0.40 +/- 0.12 microg/L (1.47 +/- 0.44 nmol/L) and 0.42 +/- 0.18 microg/L (1.56 +/- 0.67 nmol/L), respectively. Both assays exhibited high selectivity. Little or no cross reactivity to the parent compound and other metabolites was measured. The matrix effects of urine were investigated. Solid-phase extraction (SPE) strategies were used in an attempt to decrease the matrix effects and increase the sensitivity of the overall method. The limit of quantitation (LOQ) for both sFA-glycine and PBA-glycine in urine with SPE is 1.0 microg/L (3.70 nmol/L). These assays could be used as markers of exposure for monitoring biological samples.


X-ray-visible microcapsules containing mesenchymal stem cells improve hind limb perfusion in a rabbit model of peripheral arterial disease.
The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow-derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC-Xcaps). In vitro MSC-Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x-ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC-Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast-to-noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC-Xcap-treated animals versus empty Xcaps. Post-mortem immunohistopathology of vessel density by anti-CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap-MSC-treated animals versus empty Xcaps. MSC-Xcaps represent the first x-ray-visible cellular therapeutic with enhanced efficacy for PAD treatment.


Galectin-1 expression is associated with tumour immunity and prognosis in gingival squamous cell carcinoma.
Galectin-1 (Gal-1) is a β-galactoside-binding protein that overexpresses in cancer and plays pivotal roles in tumour progression. Gal-1 regulates angiogenesis and invasiveness, and suppresses tumour immunity by inducing T cell apoptosis. Several studies have examined the relationship between Gal-1 and tumour immunosuppression in vivo, but they have not examined the clinicopathological relationship between Gal-1 expression and apoptotic T cell number in human tissue. In this study, we investigated the association between Gal-1 expression and apoptotic T cells of gingival squamous cell carcinoma (GSCC), as well as other clinicopathological factors. Immunohistochemical investigation of 80 GSCC specimens using anti-Gal-1, anti-CD3, anti-CD4, anti-CD8, anti-CD34, antipodoplanin and anticleaved caspase-3 (CC-3) antibodies was performed. Relative expression levels of CD3 and CC-3, as well as CD8 and CC-3 were assessed simultaneously by double immunostaining. Gal-1 expression and T cell apoptosis were evaluated in 6 high-power fields (3 in the tumour and 3 in the stroma). Gal-1 expression in GSCC was significantly correlated with T cell infiltration (p=0.036), and apoptosis of CD3+ and CD8+ T cells (p<0.001). Moreover, Gal-1 expression was significantly correlated with lymph node metastasis (p=0.021), histological differentiation (p<0.001) and overall survival rate (p=0.021). These findings suggest that Gal-1 plays an important role in immune escape of GSCC cells, and Gal-1 expression level may be a useful clinicopathological prognostic marker for GSCC.


Positional metabolism of benzo(a)pyrene in rat placenta and maternal liver. Comparison of induction effects.
The biotransformation of [14C]benzo(a)pyrene (BP) was studied in vitro in the presence of microsomes prepared from isolated labyrinth and basal zone tissues of the rat placenta, as well as from maternal liver. Pregnant rats, day 14 of gestation, received beta-naphthoflavone (beta NF; 15 mg/kg, ip) or 3-methyl-cholanthrene (3MC; 30 mg/kg, ip). On day 15, placentae were dissected and microsomes were incubated with 17 microM [14C]BP and 2 mM NADPH. Metabolites formed in the incubation flasks were extracted and separated by HPLC utilizing a reverse phase column. Only trace BP metabolism occurred in basal zone microsomes from control, beta NF-, or 3MC-pretreated animals, as well as in labyrinth microsomes from control animals. In contrast, the preadministration of beta NF and 3MC increased labyrinth microsomal BP metabolism by 10- to 15-fold. Labyrinth and maternal liver microsomes from beta NF- and 3MC-treated animals actively converted BP to eight separate metabolites which co-chromatographed primarily with quinones and phenols. The overall formation of BP diol and phenolic metabolites by labyrinth microsomes was appreciably less than was observed for liver preparations. The very low activity of BP-4,5-oxide hydrolase in labyrinth microsomes compared to liver may in part explain the low level of formation of BP diols in placental microsomes. Labyrinth microsomes catalyzed the covalent binding of [3H]BP to calf thymus DNA, and this activity increased 5-fold following beta NF pretreatment. A comparison of induced tissues indicates that the amount of DNA binding in labyrinth microsomes is more extensive than would be expected by the level of total BP metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)


Exploring social ecological pathways from resilience to quality of life among women living with HIV in Canada.
Resilience, positive growth in contexts of stress and adversity, is shaped by social ecological factors. Among people living with HIV, resilience is associated with myriad positive health benefits and improved health-related quality of life (HR-QoL). Identifying contextual factors associated with resilience among women living with HIV (WLWH) is particularly important as this population experiences many stressors and inequalities. We examined social-ecological factors associated with resilience and its relationship with HR-QoL among WLWH. We utilized baseline survey data from a national cohort of WLWH (n = 1424) in Canada. We conducted structural equation modelling using maximum likelihood estimation methods to test the direct effects of social support and women-centred HIV care (WCHC) on resilience, and the direct effects of resilience on mental and physical HR-QoL. We also tested the indirect effects of resilience on HR-QoL via HIV disclosure concerns and economic insecurity. Participant median age was 43 years (IQR = 35-50); most participants were women of colour (29% Black; 22% Indigenous; 7% other ethnicities; 41% Caucasian). Social support and WCHC were associated with increased resilience. The direct path from resilience to mental HR-QoL was significant, accounting for the mediation effects of economic insecurity and social support. The direct path from resilience to physical HR-QoL was significant, accounting for the mediation effects of economic insecurity. Economic insecurity partially mediated the relationship between resilience and mental HR-QoL and physical HR-QoL. HIV disclosure concerns partially mediated the relationship between resilience and mental-HR-QoL. Model fit indices suggested that the model fit the data well (χ2[14] = 160.378, P < 0.001; CFI = 0.987; RMSE = 0.048 [90% CI:0.042-0.080]; SRMR = 0.036). Findings suggest social (social support) and structural (WCHC) factors increase resilience. While resilience is associated with improved HR-QoL, social (HIV disclosure concerns) and structural (economic insecurity) factors partially mediate these associations and threaten HR-QoL. Multi-level interventions can address social ecological contexts to advance resilience and HR-QoL among WLWH.


The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the β-Catenin Coactivator BCL9-2 in Breast Cancer Cells.
The WW domain containing oxidoreductase (WWOX) has recently been shown to inhibit of the Wnt/β-catenin pathway by preventing the nuclear import of disheveled 2 (DVL2) in human breast cancer cells. Here, it is revealed that WWOX also interacts with the BCL9-2, a cofactor of the Wnt/β-catenin pathway, to enhance the activity of the β-catenin-TCF/LEF (T-cell factor/lymphoid enhancer factors family) transcription factor complexes. By using both a luciferase assay in MCF-7 cells and a Xenopus secondary axis induction assay, it was demonstrated that WWOX inhibits the BCL9-2 function in Wnt/β-catenin signaling. WWOX does not affect the BCL9-2-β-catenin association and colocalizes with BCL9-2 and β-catenin in the nucleus of the MCF-7 cells. Moreover, WWOX inhibits the β-catenin-TCF1 interaction. Further examination found that HDAC3 associates with BCL9-2, enhances the inhibitory effect of WWOX on BCL9-2 transcriptional activity, and promotes the WWOX-BCL9-2 interaction, independent of its deacetylase activity. However, WWOX does not influence the HDAC3-BCL9-2 interaction. Altogether, these results strongly indicate that nuclear WWOX interacts with BCL9-2 associated with β-catenin only when BCL9-2 is in complex with HDAC3 and inhibits its transcriptional activity, in part, by inhibiting the β-catenin-TCF1 interaction. The promotion of the WWOX-BCL9-2 interaction by HDAC3, independent of its deacetylase activity, represents a new mechanism by which this HDAC inhibits transcription. The inhibition of the transcriptional activity of BCL9-2 by WWOX and HDAC3 constitutes a new molecular mechanism and provides new insight for a broad range of cancers.


The pathogenic role of autoantibodies in recurrent pregnancy loss.
In the present manuscript, we review the recent research investigating the pathogenic association between most studied autoantibodies and recurrent pregnancy loss. Pregnancy loss represents a common obstetric complication occurring in about 15%-25% of all clinically recognized pregnancies. The recurrence of pregnancy loss identifies a distinct clinical entity, that is recurrent pregnancy loss (RPL), affecting about 2%-4% of couples. Several factors, including age, chromosomal abnormalities, uterine anomalies, thrombophilic disorders, endocrinopathies, hormonal and metabolic disorders, infections, sperm quality, and lifestyle issues, are involved in RPL. The role of autoantibodies in RPL is only partially determined. In some cases (antiphospholipid antibodies [aPL]), their involvement is well established. In other cases (anti-thyroid autoantibodies, antinuclear, anti-transglutaminase, and anti-endomysial antibodies), it is still debated, despite multiple, although not fully conclusive, evidences strongly suggest a possible involvement in RPL. Further extensive research is needed to definitively confirm or exclude their actual role.


Acute normovolemic hemodilution, intraoperative cell salvage and PulseCO hemodynamic monitoring in a Jehovah's Witness with placenta percreta.
A Jehovah's Witness who had had four previous cesarean deliveries was referred to our institution for management of a complete placenta previa at 34 weeks of gestation. A subsequent ultrasound scan was suggestive of placenta percreta with bladder involvement. After erythropoietin and iron supplementation, cesarean hysterectomy was performed. Using PulseCO technology for continuous hemodynamic monitoring, preoperative acute normovolemic hemodilution and intraoperative cell salvage were used resulting in a successful cesarean hysterectomy with a 5500-mL estimated blood loss. The PulseCO system provides continuous, real-time hemodynamic data by applying pulse power analysis to the arterial pressure waveform. A bolus of oxytocin given after delivery produced profound hypotension, the hemodynamics of which were elucidated with the PulseCO system. To our knowledge, the combined use of acute normovolemic hemodilution, intraoperative cell salvage and PulseCO hemodynamic monitoring for cesarean hysterectomy has not been reported previously. These techniques may be particularly useful in managing patients who refuse blood products and/or in whom the baseline hemoglobin is suboptimal.


Giant cell reparative granuloma of the nasal cavity.
We report an unusual case of giant cell reparative granuloma (GCRG) arising in the nasal cavity of a 7-year-old girl. GCRG is an uncommon benign lesion that is most commonly found in the mandible and maxilla. The MR imaging and CT findings of this lesion, as well as GCRGs in other craniofacial bones and extragnathic sites, will be reviewed. Although rare, the imaging characteristics of GCRGs should be recognized, and this entity should be suggested when the clinical information, CT, and MR features suggest a fibrous-osseous lesion in the nasal cavity.


HIV-1 Nef dimers short-circuit immune receptor signaling by activating Tec-family kinases at the host cell membrane.
The HIV-1 virulence factor Nef promotes high-titer viral replication, immune escape, and pathogenicity. Nef interacts with interleukin-2-inducible T-cell kinase (Itk) and Bruton's tyrosine kinase (Btk), two Tec-family kinases expressed in HIV-1 target cells (CD4 T cells and macrophages, respectively). Using a cell-based bimolecular fluorescence complementation assay, here we demonstrate that Nef recruits both Itk and Btk to the cell membrane and induces constitutive kinase activation in transfected 293T cells. Nef homodimerization-defective mutants retained their interaction with both kinases but failed to induce activation, supporting a role for Nef homodimer formation in the activation mechanism. HIV-1 infection up-regulates endogenous Itk activity in SupT1 T cells and donor-derived peripheral blood mononuclear cells. However, HIV-1 strains expressing Nef variants with mutations in the dimerization interface replicated poorly and were significantly attenuated in Itk activation. We conclude that direct activation of Itk and Btk by Nef at the membrane in HIV-infected cells may override normal immune receptor control of Tec-family kinase activity to enhance the viral life cycle.


Field response of wheat to arbuscular mycorrhizal fungi and drought stress.
Mycorrhizal plants often have greater tolerance to drought than nonmycorrhizal plants. This study was conducted to determine the effects of arbuscular mycorrhizal (AM) fungi inoculation on growth, grain yield and mineral acquisition of two winter wheat (Triticum aestivum L.) cultivars grown in the field under well-watered and water-stressed conditions. Wheat seeds were planted in furrows after treatment with or without the AM fungi Glomus mosseae or G. etunicatum. Roots were sampled at four growth stages (leaf, tillering, heading and grain-filling) to quantify AM fungi. There was negligible AM fungi colonization during winter months following seeding (leaf sampling in February), when soil temperature was low. During the spring, AM fungi colonization increased gradually. Mycorrhizal colonization was higher in well-watered plants colonized with AM fungi isolates than water-stressed plants. Plants inoculated with G. etunicatum generally had higher colonization than plants colonized with G. mosseae under both soil moisture conditions. Biomass and grain yields were higher in mycorrhizal than nonmycorrhizal plots irrespective of soil moisture, and G. etunicatum inoculated plants generally had higher biomass and grain yields than those colonized by G. mosseae under either soil moisture condition. The mycorrhizal plants had higher shoot P and Fe concentrations than nonmycorrhizal plants at all samplings regardless of soil moisture conditions. The improved growth, yield and nutrient uptake in wheat plants reported here demonstrate the potential of mycorrhizal inoculation to reduce the effects of drought stress on wheat grown under field conditions in semiarid areas of the world.


Research Progress in Liver-Regenerating Microenvironment and DNA Methylation in Hepatocellular Carcinoma: The Role of Traditional Chinese Medicine.
The development, progression, recurrence, and metastasis of hepatocellular carcinoma (HCC) are closely associated with an abnormal liver-regenerating microenvironment (LRM). Therefore, preventing and reversing an abnormal LRM is a potential therapeutic strategy against HCC. Studies are increasingly focusing on the impact of regeneration, fibrosis, angiogenesis, inflammation, immunomodulation, and hepatic stem cells on HCC development and progression. As a key epigenetic mechanism, DNA methylation is extensively involved in regulating physiological and pathological pathways. In this review, we summarize recent findings on the role of DNA methylation in the fibrotic, angiogenic, inflammatory/immune, and stem cell microenvironments of HCC, and discuss new advances in Traditional Chinese Medicine (TCM) on influencing the abnormal LRM, so as to gain new insights into alleviating the abnormal LRM via regulating DNA methylation by TCM.


Identifying high school students' health behaviors: development of a survey.
A health survey developed to profile high school students for the purpose of assisting in program planning emphasized everyday health behaviors instead of focusing on high-risk behaviors (e.g., drinking, drugs, safety, or sexuality). The questionnaire was a voluntary 20-item survey that could be completed during a 15-minute homeroom period. A total of 1,401 students completed the questionnaire. Findings were shared with students, teachers, staff, and parents. Teachers and staff members were given a prepared response sheet that addressed each of the concerns identified. They were encouraged to have discussions about these behaviors with students during the homeroom period, as time and interest allowed. Response to the survey has been very positive, and a number of changes have been incorporated into the school health program as a result of the findings. One of these changes is a teen clinic that opened in April 1999. The findings also proved very useful in facilitating awareness of student behaviors and assisted in identifying ways the school nurse could assist students in improving their health and well-being.


Factors affecting the preoperative and postoperative extracellular fluid in the arm on the side of breast cancer: a cohort study.
To explore what factors affect volume of extracellular fluid (ECF) in the arm on the side of surgery pre- and postoperatively and to determine the value of knowing preoperative ECF volume for diagnosis of lymphedema postoperatively. Women (N=516) with early breast cancer were assessed preoperatively and within 4 weeks postoperatively. Baseline measures included inter-arm ECF ratio, side of cancer, number of nodes involved, and other individual characteristics. Postoperative assessment included inter-limb ECF ratio and details from surgery. The postoperative ECF ratio was categorized as to whether it exceeded previously established thresholds, and the change in ECF was categorized as to whether it exceeded 0.1. Linear regression identified which factors explained the variance for preoperative ECF ratio and the change in ratio. Chi square analysis compared whether women categorized using thresholds were the same as those whose ratio increased >0.1 postoperatively. Postoperative ECF ratio was significantly higher than the preoperative ratio (p<0.001). Women whose ECF ratio exceeded previously established thresholds were not the same as those whose ratio increased >0.1 postoperatively (p<0.001). Only the side of surgery explained the preoperative ECF measure; extent of surgery and actual weight explained the change in ECF ratio. The ECF ratio preoperatively is not affected by nodal involvement. The change in ECF ratio is affected by the extent of surgery and body mass. Change from preoperative ECF ratio did identify more women at risk for lymphedema than reliance postoperatively on thresholds, supporting preoperative measures.


Bacteria Inspired Internal Standard SERS Substrate for Quantitative Detection.
Metal-respiring bacteria are frequently used to recycle metal resources by biosynthesizing nanoparticles on its surface in environment treatment. However, further utilization of biogenetic nanoparticles through combining the advantages of both bacteria and nanoparticles is still limited. Herein, biogenetic Au@Ag nanoislands are utilized as the surface-enhanced Raman spectroscopy (SERS) substrate for quantitative detection. Specifically, Au@Ag nanoislands enhance the Raman signal via surface plasmon resonance, while biomolecules (phospholipid, tyrosine, and phenylalanine, etc.) on bacterium serve as an internal standard to eliminate the discrepancy of the target SERS intensity in different hot spots. Gene-controlled biomolecules in bacteria guarantee the reproducibility of this SERS substrate. The generality of this analytical method is demonstrated by determining rhodamine 6G, malachite green, and uric acid. This discovery solves a pervasive problem in SERS analysis through a simple biogenetic nanosystem, which opens up an avenue to address scientific challenges by using versatile organisms from nature.


Non-A to E hepatitis.
The list of possible hepatotropic viruses continues to grow with the discovery of the GB virus-C, the TT virus and the SEN virus. There is emerging data on the biology of these newly discovered :In spite of continuing research into the pathogenicity of the GB virus-C and the TT virus, definite evidence linking them to acute or chronic liver disease is lacking. The SEN virus was reported in 2000, and although there seems to be an association between virus and transfusion-related hepatitis, more data are awaited before definite conclusions can be drawn. The effect of GB virus-C, the TT virus and the SEN virus co-infection on other viral and non-viral hepatitides has also been studied in some detail. Again, there is no definite evidence so far that these viruses modify other liver diseases. At the present time, diagnostic testing for these viruses does not seem to be warranted outside of clinical studies. The discovery of these viruses, however, paves the way for further research into novel viral agents that infect humans, other among hosts.


Causal relationship between asthma and inflammatory bowel disease : A two-sample bidirectional mendelian randomization analysis.
Based on the findings of current observational studies, asthma and inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are associated; however, their causal association cannot be established due to methodological limitations. we use two-sample bidirectional mendelian randomization (MR) to overcome the confounding factors and explore the causal link between asthma and inflammatory bowel disease. After selecting asthma and IBD-related genome-wide association studies (GWAS) data and screening single nucleotide polymorphisms (SNPs), MR analysis was performed by four methods: inverse variance weighted (IVW), MR-Egger, maximum likelihood, and weighted median (WM), while Cochran's Q test was used to detect heterogeneity and MR-Egger intercept to detect horizontal pleiotropy. Finally, we used the leave-one-out method and funnel plot to perform sensitivity analysis. We screened 57, 59, and 60 SNPs in the association analysis of asthma and IBD, CD, and UC, respectively. The results of MR analysis showed that asthma only increased the risk of CD (IVW: OR = 1.1712, 95% CI = 1.0418-1.3167, P value = 0.0082; maximum likelihood: OR = 1.1739, 95% CI = 1.0428-1.3215, P value = 0.0080). Neither forward nor reverse MR analysis revealed heterogeneity or horizontal pleiotropy. Similarly, we did not find potential directional pleiotropy by funnel plot, and the leave-one-out method did not suggest a significant effect of a single SNP on the overall results. we found a negative correlation between asthma and Crohn's disease, but more research is needed to confirm this.


Low-Cost Sensors for Urban Noise Monitoring Networks-A Literature Review.
Noise pollution reduction in the environment is a major challenge from a societal and health point of view. To implement strategies to improve sound environments, experts need information on existing noise. The first source of information is based on the elaboration of noise maps using software, but with limitations on the realism of the maps obtained, due to numerous calculation assumptions. The second is based on the use of measured data, in particular through professional measurement observatories, but in limited numbers for practical and financial reasons. More recently, numerous technical developments, such as the miniaturization of electronic components, the accessibility of low-cost computing processors and the improved performance of electric batteries, have opened up new prospects for the deployment of low-cost sensor networks for the assessment of sound environments. Over the past fifteen years, the literature has presented numerous experiments in this field, ranging from proof of concept to operational implementation. The purpose of this article is firstly to review the literature, and secondly, to identify the expected technical characteristics of the sensors to address the problem of noise pollution assessment. Lastly, the article will also put forward the challenges that are needed to respond to a massive deployment of low-cost noise sensors.


Overexpression of miR-199a-5p decreases esophageal cancer cell proliferation through repression of mitogen-activated protein kinase kinase kinase-11 (MAP3K11).
Studies examining the oncogenic or tumor suppressive functions of dysregulated microRNAs (miRs) in cancer cells may also identify novel miR targets, which can themselves serve as therapeutic targets. Using array analysis, we have previously determined that miR-199a-5p was the most downregulated miR in two esophageal cancer cell lines compared to esophageal epithelial cells. MiR-199a-5p is predicted to bind mitogen-activated protein kinase kinase kinase 11 (MAP3K11) mRNA with high affinity. In this study, we observed that MAP3K11 is markedly overexpressed in esophageal cancer cell lines. Forced expression of miR-199a-5p in these cells leads to a decrease in the mRNA and protein levels of MAP3K11, due to decreased MAP3K11 mRNA stability. A direct binding interaction between miR-199a-5p and MAP3K11 mRNA is demonstrated using biotin pull-down assays and heterologous luciferase reporter constructs and confirmed by mutational analysis. Finally, forced expression of miR-199a-5p decreases proliferation of esophageal cancer cells by inducing G2/M arrest. This effect is mediated, in part, by decreased transcription of cyclin D1, due to reduced MAP3K11-mediated phosphorylation of c-Jun. These findings suggest that miR-199a-5p acts as a tumor suppressor in esophageal cancer cells and that its downregulation contributes to enhanced cellular proliferation by targeting MAP3K11.


Assessment of the variation associated with repeated measurement of gastrointestinal transit times and assessment of the effect of oral ranitidine on gastrointestinal transit times using a wireless motility capsule system in dogs.
This study aimed to evaluate the variation associated with repeated measurement of gastrointestinal (GI) transit times and the effect of oral ranitidine on GI transit times in healthy dogs using a wireless motility capsule (WMC) system. Eight privately owned healthy adult dogs were enrolled, and one developed diarrhea and was removed from the study. For the first 3 repetitions, each dog was fed a standard meal followed by oral administration of a WMC. For the 4th repetition, each dog was given ranitidine hydrochloride (75 mg PO every 12 hours) prior to and during assessment of GI transit times. Mean between-subject coefficients of variation for gastric emptying time (GET), small and large bowel transit time (SLBTT), and total transit time (TTT) were 26.9%, 32.3%, and 19.6%, respectively. Mean within-subject coefficients of variation for GET, SLBTT, and TTT were 9.3%, 19.6%, and 15.9%, respectively. Median GET, SLBTT, and TTT without ranitidine were 719, 1,636, and 2,735 minutes, respectively. Median GET, SLBTT, and TTT with ranitidine were 757, 1,227, and 2,083 minutes, respectively. No significant differences in GI transit times were found between any of the 4 repetitions. Under these experimental conditions, no significant effects of oral ranitidine on GI transit times were observed.


Strict coupling between CFTR's catalytic cycle and gating of its Cl- ion pore revealed by distributions of open channel burst durations.
CFTR, the ABC protein defective in cystic fibrosis, functions as an anion channel. Once phosphorylated by protein kinase A, a CFTR channel is opened and closed by events at its two cytosolic nucleotide binding domains (NBDs). Formation of a head-to-tail NBD1/NBD2 heterodimer, by ATP binding in two interfacial composite sites between conserved Walker A and B motifs of one NBD and the ABC-specific signature sequence of the other, has been proposed to trigger channel opening. ATP hydrolysis at the only catalytically competent interfacial site is suggested to then destabilize the NBD dimer and prompt channel closure. But this gating mechanism, and how tightly CFTR channel opening and closing are coupled to its catalytic cycle, remains controversial. Here we determine the distributions of open burst durations of individual CFTR channels, and use maximum likelihood to evaluate fits to equilibrium and nonequilibrium mechanisms and estimate the rate constants that govern channel closure. We examine partially and fully phosphorylated wild-type CFTR channels, and two mutant CFTR channels, each bearing a deleterious mutation in one or other composite ATP binding site. We show that the wild-type CFTR channel gating cycle is essentially irreversible and tightly coupled to the ATPase cycle, and that this coupling is completely destroyed by the NBD2 Walker B mutation D1370N but only partially disrupted by the NBD1 Walker A mutation K464A.


Effects of a systemic antibiotic on nasal bacterial ecology in man.
The nasal flora of coagulase-positive staphylococcus carriers and noncarriers was studied in aerobic conditions in 17 individuals. Five hundred milligrams of cephalexin was given orally four times daily for 12 days, and its effects on the nasal bacteria were determined quantitatively before, during, and after treatment. The total count obtained before the drug treatment was 5.4 x 10(6) in carriers and 3.9 x 10(6) in noncarriers. The lowest total count observed was 3 days after the cessation of the drug. The increase in gram-negative rods was seen 9 days after antibiotic therapy, not during the greatest reduction of gram-positive bacteria. Coagulase-positive cocci and diphtheroids were most sensitive to drug treatment. After 36 days, the total count was restored to pretreatment level. Diphtheroids did not return to the original number and were replaced by a corresponding increase of resistant coagulase-negative cocci. An inverse relationship between coagulase-negative cocci and lipophilic diphtheroids was seen in the anterior nares of many individuals. No gross difference in nasal ecology to differentiate carriers from noncarriers was seen.


The deubiquitinating enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase.
Rationale: Resistance to pemetrexed (PEM)-based chemotherapy is a major cause of progression in non-small cell lung cancer (NSCLC) patients. The deubiquitinating enzyme UCHL1 was recently found to play important roles in chemoresistance and tumor progression. However, the potential roles and mechanisms of UCHL1 in PEM resistance remain unclear. Methods: Bioinformatics analyses and immunohistochemistry were used to evaluate UCHL1 expression in NSCLC specimens. Kaplan-Meier analysis with the log-rank test was used for survival analyses. We established PEM-resistant NSCLC cell lines by exposing them to step-wise increases in PEM concentrations, and in vitro and in vivo assays were used to explore the roles and mechanisms of UCHL1 in PEM resistance using the NSCLC cells. Results: In chemoresistant tumors from NSCLC patients, UCHL1 was highly expressed and elevated UCHL1 expression was strongly associated with poor outcomes. Furthermore, UCHL1 expression was significantly upregulated in PEM-resistant NSCLC cells, while genetic silencing or inhibiting UCHL1 suppressed resistance to PEM and other drugs in NSCLC cells. Mechanistically, UCHL1 promoted PEM resistance in NSCLC by upregulating the expression of thymidylate synthase (TS), based on reduced TS expression after UCHL1 inhibition and re-emergence of PEM resistance upon TS restoration. Furthermore, UCHL1 upregulated TS expression, which mitigated PEM-induced DNA damage and cell cycle arrest in NSCLC cells, and also conferred resistance to PEM and other drugs. Conclusions: It appears that UCHL1 promotes PEM resistance by upregulating TS in NSCLC cells, which mitigated DNA damage and cell cycle arrest. Thus, UCHL1 may be a therapeutic target for overcoming PEM resistance in NSCLC patients.


Toward a laboratory model for psychotherapeutic treatment screening: Implementation intentions and incentives for abstinence in an analog of smoking relapse.
Despite reductions in cigarette smoking in the United States, approximately 40 million Americans are smokers. Innovative interventions are needed to help remaining smokers quit. To develop innovative interventions, precise and effective tools are needed. Here, a laboratory model of smoking relapse is assessed for its ability to detect increased resistance to smoking across 2 interventions and for its sensitivity to differing degrees of effectiveness. Nicotine-deprived participants (N = 36) completed, in randomized order, 4 smoking resistance sessions with and without implementation intentions and monetary incentives. A Cox proportional hazard mixed-effects model indicated significant differences between condition, χ²(3) = 64.87, p < .001, and the Questionnaire on Smoking Urges, χ²(1) = 4.86, p = .03. Comparisons between conditions were used to estimate the effect size of each condition on delay to smoking reinitiation. The implementation intentions intervention had a small effect (d = 0.32), the monetary incentives had a large effect (d = 0.89) and the combination of both interventions had a large effect size (d = 1.20). This initial investigation of the smoking resistance paradigm showed sensitivity to smoking reinitiation across intervention conditions. Individuals resisted smoking significantly more in the presence of monetary incentives and implementation intentions than without these interventions. These results provide support for further examination of these interventions in more translational settings and the use of this laboratory analog to screen future interventions and treatment packages. (PsycINFO Database Record


Cumulative influence of parity-related genomic changes in multiple sclerosis.
Pregnancy reduces the frequency of relapses in Multiple Sclerosis (MS) and parity also has a beneficial long term effect on disease outcome. We aimed to uncover the biological mechanisms underlying the beneficial long-term effects of parity in MS. Genome-wide gene expression revealed 574 genes associated with parity; 38.3% showed significant DNA methylation changes (enrichment p = 0.029). These genes overlapped with previous MS genes in humans and a rat MS model and were overrepresented within axon guidance (P = 1.6e-05), developmental biology (P = 0.0094) and cell-cell communication (P = 0.019) pathways. This gene regulation could provide a basis for a protective effect of parity on the long-term outcome of MS.


Comparison of clinical features among youth with tic disorders, obsessive-compulsive disorder (OCD), and both conditions.
The comorbidity of tic disorders (TD) and obsessive-compulsive disorder (OCD) has long been recognized in the clinical literature and appears to be bidirectional, affecting 20-60% of individuals with each disorder. Coffey et al. (1998) found that adults with TD+OCD had a more severe comorbidity profile than adults with OCD or TD alone. This exploratory study in children attempts to evaluate whether heightened diagnostic severity, increased comorbidity load, and lower functioning is more commonplace in youth with TD+OCD in comparison to either syndrome alone. Participants were 306 children (seeking clinical evaluation) with TD, OCD, or TD+OCD. Assessment consisted of a diagnostic battery (including structured diagnostic interviews and standardized parent-report inventories) to evaluate diagnostic severity, comorbid psychopathology, behavioral and emotional correlates, and general psychosocial functioning. Data from this study sample were not supportive of the premise that youth with both a tic disorder and OCD present with elevated diagnostic severity, higher risk-for or intensity-of comorbidity, increased likelihood of externalizing/internalizing symptomatology, or lower broad-based adaptive functioning. The OCD group had elevated rates of comorbid anxiety disorders and attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) were more prevalent among youth in the TD group. The three groups also differed on key demographic variables. Our findings suggest that, in contrast to adults, TD+OCD in children and adolescents does not represent a more severe condition than either disorder alone on the basis of diagnostic comorbidity, symptom severity, or functional impairment.


Public Health Interventions for the COVID-19 Pandemic Reduce Respiratory Tract Infection-Related Visits at Pediatric Emergency Departments in Taiwan.
Background and objective: Public health interventions such as social distancing, wearing surgical or N95 masks, and handwashing are effective in significantly reducing the risk of infection. The purpose of this article is to analyze the effect of public health interventions on respiratory tract infection-related visits to pediatric emergency departments during the COVID-19 pandemic in Taiwan. Method: Pediatric emergency department visits between January 1 2020 and April 30 2020 were included for trend analysis and compared to the same period during the past 3 years. The datasets were retrieved from Taiwan National Infectious Disease Statistics System and Kaohsiung Chang Gung Memorial Hospital. Respiratory tract infections with other diagnoses categories, including fever, asthma, and urinary tract infections, were included for subgroup analysis. Result: A significant decrease of more than 50% in respiratory tract infection-related visits was found from February to April 2020 in the national database. With regard to diagnosis category, the proportion of respiratory tract infections in Kaohsiung Chang Gung Hospital also became significantly lower in 2020 during the months of March (43.4 vs. 37.4%, p = 0.024) and April (40.1 vs. 32.2%, p < 0.001). On the other hand, the proportion of urinary tract infections was significantly higher in 2020 during March (3.7 vs. 5.2%, p = 0.033) and April (3.9 vs. 6.5%, p < 0.001), and that of asthma was also higher in April (1.6 vs. 2.6%, p = 0.025). Furthermore, the intensive care unit admission rate was relatively higher in 2020 from February, with significant differences noted in March (1.3 vs. 2.8%, p < 0.001). Conclusion: Due to public health interventions for the COVID-19 pandemic, the transmission of not only COVID-19 but also other air droplet transmitted diseases in children may have been effectively prevented.


Synergistic induction of cyclooxygenase-2 by transforming growth factor-beta1 and epidermal growth factor inhibits apoptosis in epithelial cells.
Increased expression of cyclooxygenase-2 (COX-2) expression has been observed in several human tumor types and in selected animal and cell culture models of carcinogenesis, including lung cancer. Increased expression of COX-2 and production of prostaglandins appear to provide a survival advantage to transformed cells through the inhibition of apoptosis, increased attachment to extracellular matrix, increased invasiveness, and the stimulation of angiogenesis. In the present studies, we found that transforming growth factor beta1 (TGF-beta1) and epidermal growth factor (EGF) synergistically induced the expression of COX-2 and prostaglandin E2 (PGE2) production in mink lung epithelial (Mv1Lu) cells. EGF, but not PDGF or IGF-1, was able to inhibit TGF-beta1-induced apoptosis in Mv1Lu cells and this effect was blocked by NS-398, a selective inhibitor of COX-2 activity, suggesting a possible role for COX-2 in the anti-apoptotic effect of EGF receptor ligands. The combination of TGF-beta1 and EGF also significantly induced COX-2 expression in rat intestinal epithelial (RIE-1) cells and completely prevented sodium butyrate (NaBu)-induced apoptosis. The synergistic induction of COX-2 by TGF-beta1 and EGF was not observed in R1B-L17 cells, a line derived from Mv1Lu cells that lacks the TGF-beta type-I receptor. AG1478, a selective inhibitor of EGF receptor tyrosine kinase activity, completely suppressed the induction of COX-2 expression by either EGF or TGF-beta1+EGF. Also, PD98059, a specific inhibitor of MEK/ERK pathway, and SB203580, a specific inhibitor of p38 MAPK activity, significantly inhibited the induction of COX-2 in response to combined EGF and TGF-beta1. These results suggest an important collaborative interaction of TGF-beta1 and EGF signaling in the induction of COX-2 and prostaglandin production in Mv1Lu cells.


Prevalence of familial hypercholesterolemia phenotype and ten-year risk of cardiovascular events in a working population in primary prevention: The ICARIA study.
We aimed to assess the prevalence of familial hypercholesterolaemia (FH) and to determine the incidence of cardiovascular events during a 10-year follow up in individuals with FH, compared to unaffected individuals in a working, middle-aged/young population. 576,724 active workers (36 ± 10 years-old, 70% men) without cardiovascular disease were given regular health check-ups and followed for a median of 8.5 years (i.e., 4,123,927 person-years). The FH phenotype was defined according to validated low-density lipoprotein-cholesterol thresholds, adjusted for age and sex. The primary outcome was a first cardiovascular event, whether fatal or non-fatal. We found that 707 workers (0.12% or 1 in 816 individuals) met the criteria for a heterozygous FH phenotype. During the follow-up, cardiovascular events occurred in 23 of 707 (3.25%) subjects with the FH phenotype and in 3297 of 576,017 (0.57%) subjects without the FH phenotype (p<0.001). The hazard ratio (HR, assessed with a Cox regression model) for the primary outcome was 5.7 (99% CI 3.33-9.78), before adjustments, and 4.7 (99% CI 2.62-8.58) after adjusting for sex, age, smoking, blood pressure, and diabetes. The HRs were significant for both men and women, but the magnitude of the effect was greater for men than for women. Our findings confirmed the high incidence of cardiovascular disease in individuals with untreated FH. We showed that regular health check-ups in an active, and mostly young, working population could contribute to the early identification of FH. Therefore, this approach may provide an opportunity for early treatment.


doepipeline: a systematic approach to optimizing multi-level and multi-step data processing workflows.
Selecting the proper parameter settings for bioinformatic software tools is challenging. Not only will each parameter have an individual effect on the outcome, but there are also potential interaction effects between parameters. Both of these effects may be difficult to predict. To make the situation even more complex, multiple tools may be run in a sequential pipeline where the final output depends on the parameter configuration for each tool in the pipeline. Because of the complexity and difficulty of predicting outcomes, in practice parameters are often left at default settings or set based on personal or peer experience obtained in a trial and error fashion. To allow for the reliable and efficient selection of parameters for bioinformatic pipelines, a systematic approach is needed. We present doepipeline, a novel approach to optimizing bioinformatic software parameters, based on core concepts of the Design of Experiments methodology and recent advances in subset designs. Optimal parameter settings are first approximated in a screening phase using a subset design that efficiently spans the entire search space, then optimized in the subsequent phase using response surface designs and OLS modeling. Doepipeline was used to optimize parameters in four use cases; 1) de-novo assembly, 2) scaffolding of a fragmented genome assembly, 3) k-mer taxonomic classification of Oxford Nanopore Technologies MinION reads, and 4) genetic variant calling. In all four cases, doepipeline found parameter settings that produced a better outcome with respect to the characteristic measured when compared to using default values. Our approach is implemented and available in the Python package doepipeline. Our proposed methodology provides a systematic and robust framework for optimizing software parameter settings, in contrast to labor- and time-intensive manual parameter tweaking. Implementation in doepipeline makes our methodology accessible and user-friendly, and allows for automatic optimization of tools in a wide range of cases. The source code of doepipeline is available at https://github.com/clicumu/doepipeline and it can be installed through conda-forge.


Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents.
To examine objectively measured physical activity level, organized sports participation and active commuting to school in relation to mathematic performance and inhibitory control in adolescents. The design was cross-sectional. A convenient sample of 869 sixth and seventh grade students (12-14 years) was invited to participate in the study. A total of 568 students fulfilled the inclusion criteria and comprised the final sample for this study. Mathematic performance was assessed by a customized test and inhibitory control was assessed by a modified Eriksen flanker task. Physical activity was assessed with GT3X and GT3X+ accelerometers presented in sex-specific quartiles of mean counts per minute and mean minutes per day in moderate-to-vigorous physical activity. Active commuting and sports participation was self-reported. Mixed model regression was applied. Total physical activity level was stratified by bicycling status in order to bypass measurement error subject to the accelerometer. Non-cyclists in the 2nd quartile of counts per minute displayed a higher mathematic score, so did cyclists in the 2nd and 3rd quartile of moderate-to-vigorous physical activity relative to the least active quartile. Non-cyclists in the 3rd quartile of counts per minute had an improved reaction time and cyclists in the 2nd quartile of counts per minute and moderate-to-vigorous physical activity displayed an improved accuracy, whereas non-cyclists in the 2nd quartile of counts per minute showed an inferior accuracy relative to the least active quartile. Bicycling to school and organized sports participation were positively associated with mathematic performance. Sports participation and bicycling were positively associated with mathematic performance. Results regarding objectively measured physical activity were mixed. Although, no linear nor dose-response relationship was observed there was no indication of a higher activity level impairing the scholastic or cognitive performance.


Dark lumen magnetic resonance colonography: comparison with conventional colonoscopy for the detection of colorectal pathology.
The purpose of this study was to assess the feasibility and usefulness of a new magnetic resonance (MR) colonography technique for the detection of colorectal pathology in comparison with conventional colonoscopy as the standard of reference. A total of 122 subjects with suspected colorectal disease underwent "dark lumen" MR colonography. A contrast enhanced T1w three dimensional VIBE sequence was collected after rectal administration of water. The presence of colorectal masses and inflammatory lesions were documented. Results were compared with those of a subsequently performed colonoscopy. MR colonography was found to be accurate regarding detection of clinically relevant colonic lesions exceeding 5 mm in size, with sensitivity and specificity values of 93%/100%. Dark lumen MR colonography can be considered as a promising alternative method for the detection of colorectal disease. In addition, it allows assessment of extraluminal organs.


Influence of nephrectomy on the glucoregulatory response to insulin administration in the rat.
Insulin sensitivity and resistance were examined in vivo in uremic rats by using tracer methods which permit the assessment of "non-steady-state" glucose kinetics. By relating the changes in the rates of glucose output by the liver (Ra), uptake by tissues (Rd), and metabolic clearance (MCR) to immunoreactive glucagon and insulin, it was possible to assess the tissue sensitivity to physiologic and supraphysiologic levels of these two hormones and the site of insulin resistance. The effect of an intravenous injection of insulin (100 mU) on glucose turnover was studied in acutely uremic rats 15 h after bilateral nephrectomy and in sham-operated controls, in the postabsorptive state. Glucose output by the liver and uptake by tissues were determined by the primed constant infusion technique using [3H]glucose. Under basal conditions, no significant difference in Ra and Rd between the two groups were observed, while a significant hyperglycemia and a reduced glucose metabolic clearance rate in the face of hyperglucagonemia and normal plasma insulin levels were observed in nephrectomized rats. After insulin injection, the glycemic curves were similar in the two groups, while Ra, Rd, and MCR displayed significantly lower values in nephrectomized rats in the face of higher plasma concentrations of insulin and glucagon. It was concluded that acute uremia in the rat is characterized by a loss of the normal ability of insulin to promote peripheral glucose uptake with retention of hepatic sensitivity to insulin.


Usefulness of mid-infrared spectroscopy as a tool to estimate body condition score change from milk samples in intensively-fed dairy cows.
Directly measuring individual cow energy balance is not trivial. Other traits, like body condition score (BCS) and BCS change (ΔBCS) can, however, be used as an indicator of cow energy status. Body condition score is a metric used world-wide to estimate cow body reserves and the estimation of ΔBCS was, until now, conditional on the availability of multiple BCS assessments. The aim of the present study was to estimate ΔBCS from milk mid-infrared (MIR) spectra and days in milk (DIM) in intensively-fed dairy cows using statistical prediction methods. Daily BCS was interpolated from cubic splines fitted through the BCS records and daily ΔBCS was calculated from these splines. Body condition score change records were merged with milk MIR spectra recorded on the same week. The data set comprised 37,077 ΔBCS phenotypes across 9,403 lactations from 6,988 cows in 151 herds based in Quebec (Canada). Partial least squares regression (PLSR) and a neural network (NN) were then used to estimate ΔBCS from 1) MIR spectra only, 2) DIM only, or 3) MIR spectra and DIM together. ΔBCS data in both the first 120 DIM and 305 DIM of lactation were used to develop the estimates. Daily ΔBCS had a standard deviation of 4.40*10-3 BCS units in the 120-d data set and of 3.63*10-3 BCS units in the 305-d data set. 4-fold cross-validation was used to calibrate and test the prediction equations. External validation was also conducted using more recent years of data. Irrespective of whether based on the first 120 or 305 DIM, or when MIR spectra only, DIM only or MIR spectra and DIM were jointly used as prediction variables, NN produced the lowest root mean square error (RMSE) of cross-validation (1.81*10-3 BCS units and 1.51*10-3 BCS units, respectively, using the 120-d and 305-d data set). Relative to predictions for the entire 305 DIM, the RMSE of cross-validation was 15.4% and 1.5% lower in the first 120 DIM when using PLSR and NN, respectively. Predictions from DIM only were more accurate than those using just MIR spectra data but, irrespective of the data set and of the prediction model used, the combining DIM information with MIR spectral data as prediction variables reduced the RMSE compared with inclusion of DIM alone, albeit the benefit was small (the RMSE from cross-validation was reduced up to 5.5% when DIM and spectral data were jointly used as model features instead of DIM only). However, when predicting extreme ΔBCS records, the MIR spectral data was more informative than DIM. Model performance when predicting ΔBCS records in future years was similar to that from cross-validation demonstrating the ability of MIR spectra of milk and DIM combined to estimate ΔBCS, particularly in early lactation. This can be used to routinely generate estimates of ΔBCS to aid in day-to-day individual cow management.


Comparative study of the glycosylation of platelet glycoprotein GPIIb/IIIa and the vitronectin receptor. Differential processing of their beta-subunit.
The platelet glycoprotein GPIIb/IIIa and the vitronectin receptor (VNR) are alpha beta-heterodimeric proteins and share the same beta-subunit. By performing swainsonine treatment and digestion with endoglycosidase H (Endo H), we showed that the heavy chains of GPIIb and VNR alpha are glycosylated by complex-type oligosaccharide chains, and provided the first evidence for the presence of one complex carbohydrate residue on their light chains. The proteolytic cleavage of pro-GPIIb and the acquisition of Endo H-resistance are independent events occurring in the same Golgi compartment. We demonstrated the Endo H-sensitivity of GPIIIa and VNR beta in all cellular systems tested. In addition, this beta-subunit is differently glycosylated according to whether it is associated with GPIIb or VNR alpha, one carbohydrate chain being processed to the complex type on GPIIIa, but not on VNR beta.


National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness- Alzheimer's Disease (CATIE-AD): baseline characteristics.
CATIE-AD was a multicenter effectiveness trial of atypical antipsychotics in patients with agitation and psychosis associated with AD who resided in the community. The study enrolled 421 participants. In this paper we present and discuss baseline characteristics of participants (demographics, cognitive, behavioral, and functional assessments), caregivers (demographics and caregiver burden) and settings at randomization. Those enrolled suffered from a wide range of cognitive impairment, were medically complex and experienced acute psychopathology requiring intervention with atypical antipsychotics. Family members providing the equivalent of institutional care experienced significant depression and caregiver burden. With the increasing prevalence of AD, clinicians and health care planners should look into future needs of those AD sufferers who are residing in community.


Exploiting Locality in Full Configuration Interaction Quantum Monte Carlo for Fast Excitation Generation.
In this paper, we propose an improved excitation generation algorithm for the full configuration interaction quantum Monte Carlo method, which is particularly effective in systems described by localized orbitals. The method is an extension of the precomputed heat-bath strategy of Holmes et al., with more effective sampling of double excitations and a novel approach for nonuniform sampling of single excitations. We demonstrate the effectiveness of the algorithm for a chain of 30 hydrogen atoms with atom-localized orbitals, a stack of benzene molecules, and an Fe(II)-porphyrin model complex, whereby we show an overall efficiency gain by a factor of two to four, as measured by variance reduction per wall-clock time.


Involuntary eyelid closure after STN-DBS: evidence for different pathophysiological entities.
Involuntary eyelid closure (IEC) may occur after deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) and is often categorised as apraxia of lid opening (ALO), albeit the appropriateness of this term is under debate. To gain insight into the hitherto undefined pathophysiology of IEC after STN-DBS, we performed a comprehensive clinical and electrophysiological characterisation of lid function in a total of six PD patients. The study was carried out in six PD patients who developed IEC after STN-DBS. They underwent neurological examination and electromyography recording of activity in the orbicularis oculi muscle (OO) upon varying stimulation patterns. Intraoperative studies were performed in one patient. Increasing STN-DBS intensity induced IEC in four patients, whereas it improved the condition in two. Needle EMG showed tonic hyperactivity of the OO in STN-DBS induced IEC, while variable patterns of OO activity (irregular and tonic) were seen in patients with STN-DBS-relieved IEC. Intraoperative analysis in one patient showed evidence for IEC being induced by activation of corticobulbar fibres. We identified two groups of IEC after STN-DBS based on clinical and EMG patterns: (1) STN-DBS induced IEC associated with tonic OO overactivity and (2) STN-DBS relieved IEC presenting with variable EMG patterns. Our findings provide relevant information on pathophysiology of STN-DBS related IEC and implications for its therapeutic management.


Using erbium-doped yttrium aluminum garnet laser irradiation in different energy output levels versus ultrasonic in removal of root canal filling materials in endodontic retreatment.
The objective of this study was to evaluate the efficacy of erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation in different energy outputs versus ultrasonic in gutta-percha removal during the endodontic retreatment. A total of 21 extracted human lower premolars were divided into three groups (n = 7). Following the standardized preparation of the root canals with Wave One Rotary system and obturation with gutta-percha: Group I was treated with ultrasonic, Group II by Er:YAG laser with 40 mJ/Pulse, and Group III by Er:YAG laser with 50 mJ/Pulse for the removal of gutta-percha from the canals. Two extra teeth were treated by Er:YAG laser with 135 mJ/Pulse as control group. For all groups, time for gutta-percha removal was recorded. Samples were then splited into two halves and tested by scanning electron microscope and stereomicroscopic evaluation under different magnification power to observe the efficacy of each method used in the removal of gutta-percha. Statistical analysis of Kruskal-Wallis suggested that there are significant difference between the groups in relation to removal time (P < 0.05) and 2 × 2 Mann-Whitney U-test among the groups revealed that there is no significant difference between 40 and 50 mJ laser outputs (P > 0.05), but ultrasonic versus 40 and/or 50 mJ laser outputs were significantly different (P < 0.05). Er:YAG laser beam was not so efficient when compared to ultrasonic to reach the deeper parts of the canals as it was asserted, thermal side effects and burning damages were observed on the root canal dentinal walls. Moreover, the delivery system was not flexible enough to compensate the curvature of the canal system even though we used more straight canals as the sample ones as well as more time-consuming than the ultrasonic and more clinical time, rendering it to be less efficient in the removal of the obturation material during endodontic retreatment procedures.


An individual-based model of seed- and rhizome-propagated perennial plant species and sustainable management of Sorghum halepense in soybean production systems in Argentina.
Perennial plants which propagate through both seeds and rhizomes are common in agricultural and nonagricultural systems. Due to their multifaceted life cycle, few population models are available for studying such species. We constructed a novel individual-based model to examine the effects of ecological, evolutionary, and anthropogenic factors on the population dynamics of perennial species. To exemplify the application of the model, we presented a case study of an important weed, Sorghum halepense (L.) Pers. (Johnsongrass), in soybean productions in Argentina. The model encompasses a full perennial weed life cycle with both sexual (seeds) and asexual (rhizomes) propagations. The evolution of herbicide resistance was modeled based on either single genes or quantitative effects. Field experiments were conducted in the species' native environment in Argentina to parameterize the model. Simulation results showed that resistance conferred by single-gene mutations was predominantly affected by the initial frequency of resistance alleles and the associated fitness cost. Population dynamics were influenced by evolved resistance, soil tillage, and rhizome fecundity. Despite the pivotal role of rhizomes in driving the population dynamics of Johnsongrass, most herbicides target the aboveground biomass, and chemical solutions to control rhizomes are still very limited. To maintain effective (short-term) and sustainable (long-term) weed management, it is recommended to combine soil tillage with herbicide applications for suppressing the rhizomes and delaying the evolution of resistance. This novel model of seed- and rhizome-propagated plants will also be a useful tool for studying the evolutionary processes of other perennial weeds, cash crops, and invasive species.


[The women workforce in Dentistry in Araçatuba - SP].
A process of femininity has been recently occurring in the professions, mainly in the health field. In this study, the authors aimed at analyzing the dental practice by women as regards the income, degree of satisfaction and problems they have been facing. One hundred female dentists from Araçatuba, SP, were interviewed and answered a questionnaire designed for that purpose, which contained thirty questions. The results showed that 87% are not the main source of income of the family. Among the interviewed, 38% have an income below R$ 1500; 44% agreed that the income from dental practice is not enough. From all, 78% considered themselves as satisfied with the profession, however 58.2% would not stimulate their children to pursue the dental career. The main complains are the low income and saturation of the profession. Concerning health, 50.5% have some professional diseases, mainly backache and varicose veins. It was concluded that, even though most subjects stated to be satisfied with the profession, aspects such as financial and health problems, complains and no recommendation of this career for their children demonstrate their sometimes unconscious dissatisfaction with the dental practice.


The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression.
The nonhistone chromosomal proteins high mobility group I(Y) [HMG I(Y)] have been shown to function as architectural transcription factors facilitating enhanceosome formation on a variety of mammalian promoters. Specifically, they have been shown to act as a "molecular glue" mediating protein-protein and protein-DNA contacts within the enhanceosome complex. HMG I(Y) proteins are expressed at high levels in embryonic and transformed cells and have been implicated in transcriptional regulation in these cells. Terminally differentiated cells, however, have been reported to express only minimal, if any, HMG I(Y). In contrast to these observations, we show here that adult mouse retinal photoreceptors, which are terminally differentiated cells, express high levels of these proteins. Using retinoblastoma cells as an approximate model, we further demonstrate in transiently transfected cells that inhibition of HMG I(Y) expression and mutation of HMG I(Y) binding sites significantly reduce rhodopsin promoter activity. DNase I footprint analysis indicates that HMG I protein interacts with a discrete site within the rhodopsin proximal promoter. This site overlaps with the binding site for Crx, a paired-like homeodomain transcription factor that is essential for photoreceptor functioning and that when mutated causes several forms of human photoreceptor degeneration. Both biochemical and functional experiments demonstrate that HMG I(Y) physically associate with Crx and that their interaction with DNA is required for high-level transcription of the rhodopsin gene. These data provide the first demonstration that HMG I(Y) can be important for gene activation in terminally differentiated cells.


Evaluation of an automated instrument for viability and concentration measurements of cryopreserved hematopoietic cells.
Two important parameters for determination of deleterious effects of cellular processing on hematopoietic progenitor cells are cell viability and concentration. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital evaluated the Beckman Coulter Vi-Cell automated instrument for the measurement of these two parameters. Using 33 thawed hematopoietic progenitor cell samples, automated Vi-Cell viability results were compared to those obtained using the standard trypan blue manual method. In addition, cell concentrations from these samples were compared with results from the Model Z2 Coulter Counter. Chinese Hamster Ovary cells were used for the evaluation of Vi-Cell linearity at the Beckman Coulter Cellular Analysis Development Center. Significant correlation was obtained when the two methods were compared for both cell concentration and percentage viability (P < .0001). The results of the linearity study indicated that the Vi-Cell is linear from approximately 5 x 10(4) to greater than 1 x 10(7) cells/mL. The Vi-Cell uses sample volumes as low as 0.5 mL; cell diameters may be 2 to 70 microns. The Vi-Cell automated instrument offers many significant advantages for cell analyses in today's busy laboratory environment.


A single-point modeling approach for the intercomparison and evaluation of ozone dry deposition across chemical transport models (Activity 2 of AQMEII4).
A primary sink of air pollutants and their precursors is dry deposition. Dry deposition estimates differ across chemical transport models, yet an understanding of the model spread is incomplete. Here, we introduce Activity 2 of the Air Quality Model Evaluation International Initiative Phase 4 (AQMEII4). We examine 18 dry deposition schemes from regional and global chemical transport models as well as standalone models used for impact assessments or process understanding. We configure the schemes as single-point models at eight Northern Hemisphere locations with observed ozone fluxes. Single-point models are driven by a common set of site-specific meteorological and environmental conditions. Five of eight sites have at least 3 years and up to 12 years of ozone fluxes. The interquartile range across models in multiyear mean ozone deposition velocities ranges from a factor of 1.2 to 1.9 annually across sites and tends to be highest during winter compared with summer. No model is within 50 % of observed multiyear averages across all sites and seasons, but some models perform well for some sites and seasons. For the first time, we demonstrate how contributions from depositional pathways vary across models. Models can disagree with respect to relative contributions from the pathways, even when they predict similar deposition velocities, or agree with respect to the relative contributions but predict different deposition velocities. Both stomatal and nonstomatal uptake contribute to the large model spread across sites. Our findings are the beginning of results from AQMEII4 Activity 2, which brings scientists who model air quality and dry deposition together with scientists who measure ozone fluxes to evaluate and improve dry deposition schemes in the chemical transport models used for research, planning, and regulatory purposes.