Macular superficial vascular density on optical coherence tomography angiography in children with unilateral anisometropic and bilateral hyperopic amblyopia.
We analyzed whether macular superficial vascular density (SVD) and foveal vascular zone (FAZ) on optical coherence tomography angiography (OCTA) can distinguish between bilateral ametropic and anisometropic amblyopia. We included 42, 33, and 50 eyes in the bilateral ametropic amblyopia, anisometropic amblyopia, and normal control groups, respectively. Using macular swept-source optical coherence tomography angiography, we measured and analyzed the superficial FAZ areas and five sectoral macular SVDs after magnification correction. The anisometropic amblyopic eye group showed significantly increased foveal SVDs (p < 0.001) and significantly decreased superficial FAZ areas (p < 0.001), compared with the remaining groups. Additionally, the bilateral ametropic amblyopia group had significantly decreased nasal SVDs. SVDs and superficial FAZ areas differed among hyperopic amblyopia subtypes. These findings may reflect vascular distribution differences and macular changes in hyperopic amblyopia subtypes compared with normal eyes.


Impact of pathologic complete response on survival after neoadjuvant chemotherapy in early-stage breast cancer: a population-based analysis.
Achieving a pathologic complete response (pCR) has been associated with improved long-term outcomes in clinical trials. However, the benefit of achieving pCR across subtypes and its prognostic effect on real-world outcomes has not been well described. A retrospective analysis of the Breast Cancer Outcomes Unit database was undertaken to identify patients with stage I-III breast cancer treated with neoadjuvant chemotherapy from 2005 to 2010 in British Columbia. Patients were separated into two groups: those with pCR and those with residual invasive disease in the breast/axillary lymph nodes (RD). The primary endpoint was relapse-free survival (RFS). Key secondary endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Of 267 patients identified, 74 patients (28%) achieved pCR and 193 patients (72%) had RD. Median follow-up was 7.5 years. The 5-year RFS was higher in the pCR group compared to the RD group (84% vs 70%; HR 0.45, p = 0.011). The 5-year BCSS was also higher in the pCR group than in the RD group (90% vs 77%; HR 0.39, p = 0.014). In multivariable analyses, pCR was associated with improved RFS (HR 0.39, p = 0.0077) and BCSS (HR 0.35, p = 0.015), whereas traditional pathological prognostic factors were not. Patients with TNBC who achieved pCR had improved RFS and BCSS compared to those with RD (HR 0.26, p = 0.020 and HR 0.35, p = 0.090, respectively). A similar but non-statistically significant trend was seen in the HER-2-positive and ER + subtypes. Achieving pCR after neoadjuvant chemotherapy was associated with clinically meaningful improvements in survival parameters in a real-world setting. The cumulative data support pCR as a valid surrogate endpoint in both clinical trials and population-based settings.


Differential regulation of the phosphorylation of Trimethyl-lysine27 histone H3 at serine 28 in distinct populations of striatal projection neurons.
Phosphorylation of histone H3 (H3) on serine 28 (S28) at genomic regions marked by trimethylation of lysine 27 (H3K27me3) often correlates with increased expression of genes normally repressed by Polycomb group proteins (PcG). We show that amphetamine, an addictive psychostimulant, and haloperidol, a typical antipsychotic drug, increase the phosphorylation of H3 at S28 and that this effect occurs in the context of H3K27me3. The increases in H3K27me3S28p occur in distinct populations of projection neurons located in the striatum, the major component of the basal ganglia. Genetic inactivation of the protein phosphatase-1 inhibitor, dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), reduces the phosphorylation of H3K27me3S28 produced by amphetamine and haloperidol. In contrast, knockout of the mitogen- and stress activated kinase 1 (MSK1), which is implicated in the phosphorylation of histone H3, decreases the effect of amphetamine, but not that of haloperidol. Chromatin immunoprecipitation analysis shows that amphetamine and haloperidol increase the phosphorylation of H3K27me3S28 at the promoter regions of Atf3, Npas4 and Lipg, three genes repressed by PcG. These results identify H3K27me3S28p as a potential mediator of the effects exerted by amphetamine and haloperidol, and suggest that these drugs may act by re-activating PcG repressed target genes.


Main features and contamination of sealed soils in the east of Moscow city.
The aim of this paper is to characterize the main properties and level of pollution of sealed soils in different land use zones of the Eastern administrative district (EAD) of Moscow. In 2016-2017 overall, 47 samples were taken from 35 soil pits. The list of soil properties analyzed included actual acidity, organic carbon content, particle-size distribution, and degree of salinity. Pollution of sealed soils with petroleum products (PPs), benzo[a]pyrene (BaP) and heavy metals and metalloids (HMMs) was evaluated. Sealed soils are characterized by the medium organic matter content (2.24%), alkaline reaction (pH 8.0), sandy loamy texture, and the absence of soluble salts in the upper part of the profile. The pronounced technogenic anomalies of hydrocarbons are mainly formed in the sealed soils of the industrial and traffic land use zones. The mean content of BaP in the sealed soils is 56 times higher than that in the background soils, it exceeds MPC by 9.5 times. The concentrations of most HMMs in the sealed soils exceed the background level by two-four times. The most intense accumulation of As, Ba, Cr, Cu, Ni, Pb, Sb, and Sn takes place in the industrial zone with the high degree of sealing. The hygienic standards for BaP and PPs contents approved in the Russian Federation in the sealed soils of EAO are exceeded by almost ten times. Maximum permissible concentrations are also exceeded for a large group of HMMs. The high contamination of the sealed soils can create dangerous ecological situation in the EAD if road covering will be removed and pollutants begin to migrate.


Cerebrovascular permeability and brain edema after cortical photochemical infarcts in the rat.
The importance of protein extravasation for the development of vasogenic brain edema is still controversial. We, therefore, assessed the cerebrovascular permeability to serum proteins in relation to the development and resolution of brain edema in a photochemical cortical lesion in the rat. Cortical infarction was induced by in situ thrombosis using an argon laser beam aimed at the exposed parietal bone in animals given rose bengal i.v. The histology and the cerebrovascular permeability to serum proteins were scrutinized from 2 h to 3 weeks after the insult. The presence of serum proteins was demonstrated by an immunoperoxidase technique. The cerebral water content was estimated by specific gravity measurements of the cortical tissue in a kerosene-monobromobenzene gradient column from 2 h to 7 days after infarction. The blood-brain barrier was permeable to proteins at 2 h following the insult and proteins spread into the medial and lateral tissue reaching a maximum at 24 h. The specific gravity did not deviate from control values at 2 h. After 8 h the specific gravity of the lesion decreased with smaller decreases in the immediately adjacent tissue. At 24 h the changes in specific gravities reached a maximum in all regions except the immediately lateral area. The edema was generally worse in tissue medial to rather than lateral to the infarct. The degradation of serum proteins and the resolution of the brain edema followed the same time course with partial resolution of 72 h. By 1 week serum proteins and edema were confined to the central necrotic core. The results suggest a relationship between cerebrovascular permeability and cerebral edema in photochemical cortical infarction.


Alarming trends in pediatric overweight in the United States.
A comprehensive review of the pediatric overweight literature was undertaken to examine secular changes in the prevalence of pediatric overweight, the current magnitude and scope of pediatric overweight, and the identity of high-risk groups in the U.S. Articles published in the last two decades and studies of nationally representative numbers of children were highlighted. An unprecedented three-fold increase in the prevalence of pediatric overweight has occurred in recent decades in the U.S. and evidence suggests that this trend is continuing unabated. While no sociodemographic or racial group has escaped this trend, particularly at risk are African American girls, Hispanic girls and boys, and children from low-income house-holds. The rising prevalence of pediatric overweight in the U.S. is a harbinger of increases in diabetes, cardiovascular disease and numerous other health problems. Furthermore, disparities in pediatric overweight along ethnic and socio-economic lines are expected to further exacerbate current disparities in rates of chronic disease. Strategies and programs to prevent overweight among children are urgently needed.


Synthesis of ruthenium polypyridine complexes with benzyloxyl groups and their antibacterial activities against Staphylococcus aureus.
Four new ruthenium polypyridyl complexes, [Ru(bpy)2(BPIP)](PF6)2 (Ru(II)-1), [Ru(dtb)2(BPIP)](PF6)2 (Ru(II)-2), [Ru(dmb)2(BPIP)](PF6)2 (Ru(II)-3) and [Ru(dmob)2(BPIP)](PF6)2 (Ru(II)-4) (bpy = 2,2'-bipyridine, dtb = 4,4'-di-tert-butyl-2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dmob = 4,4'-dimethoxy-2,2'-bipyridine and BPIP = 2-(3,5-bis(benzyloxyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) had been synthesized and characterized. Their antimicrobial activities were investigated against Staphylococcus aureus (S. aureus) and four complexes showed obvious antibacterial effect, especially the minimum inhibition concentration (MIC) value of Ru(II)-3 was only 4 μg/mL. In addition, Ru(II)-3 was able to kill bacteria quickly and inhibit the formation of biofilm. Meanwhile, the cooperative effect between Ru(II)-3 and general antibiotics were tested and the results showed that Ru(II)-3 could enhance the susceptibility of S. aureus to different types of antibiotics. Most importantly, Ru(II)-3 hardly showed cytotoxicity to mammalian erythrocytes both in homelysis experiment and G. mellonella model. After being injected with high doses of the Ru(II)-3in vivo, the G. mellonella worms still exhibited high survival rates. Finally, a mouse skin infection model and G. mellonella infection model was built to determine the antibacterial activity of Ru(II)-3in vivo. The antibacterial mechanism of Ru(II)-3 was probably related to the membrane-disruption. Taken together, ruthenium polypyridine complexes with benzyloxyl groups had the potential to develop an attractive and untraditional antibacterial agent with new mode of action.


Monophyletic blowflies revealed by phylogenomics.
Blowflies are ubiquitous insects, often shiny and metallic, and the larvae of many species provide important ecosystem services (e.g., recycling carrion) and are used in forensics and debridement therapy. Yet, the taxon has repeatedly been recovered to be para- or polyphyletic, and the lack of a well-corroborated phylogeny has prevented a robust classification. We here resolve the relationships between the different blowfly subclades by including all recognized subfamilies in a phylogenomic analysis using 2221 single-copy nuclear protein-coding genes of Diptera. Maximum likelihood (ML), maximum parsimony (MP), and coalescent-based phylogeny reconstructions all support the same relationships for the full data set. Based on this backbone phylogeny, blowflies are redefined as the most inclusive monophylum within the superfamily Oestroidea not containing Mesembrinellidae, Mystacinobiidae, Oestridae, Polleniidae, Sarcophagidae, Tachinidae, and Ulurumyiidae. The constituent subfamilies are re-classified as Ameniinae (including the Helicoboscinae, syn. nov.), Bengaliinae, Calliphorinae (including Aphyssurinae, syn. nov., Melanomyinae, syn. nov., and Toxotarsinae, syn. nov.), Chrysomyinae, Luciliinae, Phumosiinae, Rhiniinae stat. rev., and Rhinophorinae stat. rev. Metallic coloration in the adult is shown to be widespread but does not emerge as the most likely ground plan feature. Our study provides the first phylogeny of oestroid calyptrates including all blowfly subfamilies. This allows settling a long-lasting controversy in Diptera by redefining blowflies as a well-supported monophylum, and blowfly classification is adjusted accordingly. The archetypical blowfly trait of carrion-feeding maggots most likely evolved twice, and the metallic color may not belong to the blowfly ground plan.


TUG1 Regulates Pulmonary Arterial Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension.
Pulmonary arterial hypertension (PAH) is a progressive disease, characterized by a persistent elevation of pulmonary arterial pressure and pulmonary vascular remodelling. Recent studies implicated that long noncoding RNAs (lncRNAs) play important roles in the development of various diseases. However, the underlying mechanisms of lncRNAs in PAH remain unclear. Here we show evidence for the modulation of human pulmonary smooth muscle cell (HPASMC) proliferation and vascular remodelling by lncRNA taurine upregulated gene1 (TUG1). TUG1 expression and localization was detected by real-time polymerase chain reaction (PCR) and fluorescence in situ hybridization. Proliferation and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), western blot, bromodeoxyuridine incorporation, flow cytometry, scratch-wound assay, 4',6-diamidino-2-phenylindole (DAPI), and caspase-3 activity. Luciferase activity and microscale thermophoresis were used to identify biomolecular interactions. The right ventricular systolic pressure and right ventricular hypertrophy were measured to evaluate cardiopulmonary function. TUG1 was upregulated in the pulmonary arteries of mice after a hypoxic assault and showed a significant increase in patients with PAH. TUG1 knockdown significantly prevented the development of PAH in vivo. Moreover, TUG1 promoted the proliferative responses of HPASMCs, including cell viability, 5-bromodeoxyuridine incorporation, the expression of proliferating cell nuclear antigen, and cell-cycle progression. All these functions of TUG1 were likely to be associated with miR-328. The present study indicates that TUG1, a novel potential target for the treatment of PAH, is necessary for HPASMC proliferation and pulmonary vascular remodelling.


Autonomic dysfunction in palmar hyperhidrosis.
The autonomic (including sudomotor, baroreceptor, and vasomotor) functions were assessed in 3 groups of individuals, comprising normal, hyperhidrotic, and denervated subjects. The normal group had no palmar hyperhidrosis, with intact T2-3 ganglia, the hyperhidrotic group had palmar hyperhidrosis with intact T2-3 ganglia, and the denervated group had palmar hyperhidrosis treated with T2-3 ganglionectomy. Compared with both the normal and hyperhidrotic subjects, the denervated subjects had a much smaller sweating response of both the forehead, the upper chest region and the upper extremities, and a much greater sweating response of both the lateral lumbar and ventral thigh regions in response to body exercise. In addition, cardiovascular responses to either the Valsalva manoeuver, face immersion, or finger immersion were evaluated in these groups of subjects. When compared with those of either the normal or the denervated subjects, the hyperhidrotic subjects had less reflex bradycardia in response to either Valsalva manoeuver or face immersion. In contrast, when compared with those of either the normal or the denervated subjects, the hyperhidrotic subjects had a higher degree of cutaneous vasoconstriction in response to finger (or cold) immersion. The data indicate that the sympathetic fibers passing through the T2-3 ganglia play an important role in the elaboration or modulation of autonomic function elsewhere. Probably, the hyperhidrotic subjects have an over-functioning of the sympathetic nervous fibers which pass through the T2-3 ganglia, which leads to autonomic dysfunction. The autonomic dysfunctions observed in the hyperhidrotic subjects could be eliminated after the interruption of the excessive sympathetic activities passing through the T2-3 ganglia level. A preliminary report of this work was delivered at the 15th Congress of the Pan-Pacific Surgical Association, January 12-18, 1980 and the 12th World Congress of Neurology, September 20-25, 1981.


Eating behaviour and adherence to diet in patients with Type 2 diabetes mellitus.
To assess restrained, emotional and external eating behaviour in patients newly diagnosed with Type 2 diabetes compared with the general population, and to assess the relationship of eating behaviour to changes in fat and energy. We assessed emotional, external, and restrained eating behaviour and measured fat and energy intake in a cohort of patients with newly diagnosed Type 2 diabetes. Data from a comparable sample of the general population served as reference figures. We calculated correlation coefficients of the three different types of eating behaviour at diagnosis between: (i) energy and fat intake at diagnosis and (ii) changes in energy and fat intake between diagnosis and both 8 weeks and 4 years later. In addition, we used a stepwise multiple regression model with energy and fat intake or changes in energy and fat intake as dependent variables. The distribution of the three types of eating behaviour was similar in patients with Type 2 diabetes and the general population. Emotional and external eating was associated with increased intake of energy and fat. Conversely, restrained eating showed an inverse correlation with energy and fat intake. External eating, but not emotional eating, showed a statistically significant relation with a decrease in energy intake in women. We found no statistically significant correlations between eating behaviour (measured at diagnosis) and changes in energy and fat intake between diagnosis and 4 years. Patients newly diagnosed with Type 2 diabetes have similar eating behaviour compared with the general population. At diagnosis, external eating behaviour and emotional eating behaviour are associated with high-energy intake and restrained eating behaviour with low-energy intake. Women with high scores for emotional eating behaviour seem to be less able to make initial dietary changes after being diagnosed and having received dietary advice.


A multiple-staining ultrastructural procedure simultaneously detecting three membrane antigens on suspended cells by monoclonal antibodies and pre-embedding immunogold labelling.
A triple ultrastructural immunogold staining method for the simultaneous demonstration of three surface antigens of peripheral blood mononuclear cells at the electron microscope level is described. A six-step pre-embedding immunoelectron microscopy procedure was developed, using commercially available reagents. The CD11b antigen was first detected, through a two-step (indirect) method with 40 nm-sized gold particles; after a blocking step, the HLA-DR surface antigen was subsequently detected, through a two-step (biotin-streptavidin) method with 20 nm-sized gold particles; the CD4 antigen was finally detected, through a one-step (direct) method, using 5 nm-sized gold particles. Electron microscopic examination revealed firstly the presence of a triple-labelled cell subpopulation, which showed gold granules of the three sizes simultaneously decorating the cell membrane. Thus, the cells of such a subset simultaneously expressed the three antigens investigated. In contrast, either gold particles of only one size or no gold particles were observed on the cell surface of other subpopulations. This technique is a model demonstrating the importance of varying the size of particles in pre-embedding gold immunoelectron microscopy for a better analysis of the expression of surface antigens in isolated cells.


Rotating platform knees: an emerging clinical standard: in opposition.
As surgeons, we share the common goals of making total knee arthroplasty as reliable, as reproducible, and as durable as we can. For that reason, we are almost compelled to investigate the rotating platform knee because of the contentions that it might improve patellar tracking, decrease lateral release rates, improve flexion, or perhaps give better wear characteristics over the long term. But when we take a step back and carefully examine the scientific data from 20 years of clinical experience with the rotating platform knee, the data speak for itself. To date, there are no demonstrated clinical advantages in regard to wear, survivorship, kinematics, range of motion, or patellar function. The rotating platform design then is really just another knee design, clinically indistinguishable from many well-functioning, fixed-bearing total knee designs.


The development and clinical applications of proteomics: an Indian perspective.
Proteomic research has been extensively used to identify potential biomarkers or targets for various diseases. Advances in mass spectrometry along with data analytics have led proteomics to become a powerful tool for exploring the critical molecular players associated with diseases, thereby, playing a significant role in the development of proteomic applications for the clinic. This review presents recent advances in the development and clinical applications of proteomics in India toward understanding various diseases including cancer, metabolic diseases, and reproductive diseases. Keywords combined with 'clinical proteomics in India' 'proteomic research in India' and 'mass spectrometry' were used to search PubMed. The past decade has seen a significant increase in research in clinical proteomics in India. This approach has resulted in the development of proteomics-based marker technologies for disease management in the country. The majority of these investigations are still in the discovery phase and efforts have to be made to address the intended clinical use so that the identified potential biomarkers reach the clinic. To move toward this necessity, there is a pressing need to establish some key infrastructure requirements and meaningful collaborations between the clinicians and scientists which will enable more effective solutions to address health issues specific to India.


On-line hyphenation of quantum cascade laser and capillary electrophoresis.
We report the first successful hyphenation of a Fabry Pérot quantum cascade (QC) laser to a capillary electrophoresis system. This involved use of a dedicated IR-transparent flow cell, made of CaF2, constructed by means of SU-8 based lithography and low temperature wafer bonding techniques. Adenosine, guanosine, xanthosine and adenosine-5'-monophosphate were separated in a borate-containing separation electrolyte (10 mM, pH 9.3). Functional group (carbohydrate) detection was accomplished by use of the 1080 cm(-1) emission line of the available QC-laser. The assessable optical path length could be increased, from the normally available 10-15 microm in CE-FTIR analyses, to 60 microm using this powerful mid-infrared laser and aqueous solutions.


Significance of ascitic fluid and peritoneal washing cytology in ovarian tumor diagnosis.
The results of the cytological test on 179 ascitic fluids and 88 peritoneal washes of patients suspected to have ovarian tumors are critically reviewed to illustrate the difficulties, limitations and future possibilities of this technique. Tissue correlation was available in all cases. The data was evaluated in order to obtain information as to the accuracy, sensitivity and specificity of cytological examination, both in ascitic fluids and in peritoneal washings. A correct diagnosis as to the ovarian tumor histotype was obtained in more than 80 per cent of the cases.


Gravitation field algorithm and its application in gene cluster.
Searching optima is one of the most challenging tasks in clustering genes from available experimental data or given functions. SA, GA, PSO and other similar efficient global optimization methods are used by biotechnologists. All these algorithms are based on the imitation of natural phenomena. This paper proposes a novel searching optimization algorithm called Gravitation Field Algorithm (GFA) which is derived from the famous astronomy theory Solar Nebular Disk Model (SNDM) of planetary formation. GFA simulates the Gravitation field and outperforms GA and SA in some multimodal functions optimization problem. And GFA also can be used in the forms of unimodal functions. GFA clusters the dataset well from the Gene Expression Omnibus. The mathematical proof demonstrates that GFA could be convergent in the global optimum by probability 1 in three conditions for one independent variable mass functions. In addition to these results, the fundamental optimization concept in this paper is used to analyze how SA and GA affect the global search and the inherent defects in SA and GA. Some results and source code (in Matlab) are publicly available at http://ccst.jlu.edu.cn/CSBG/GFA.


[Morphometric analysis of the human endometrium during the implantation window. Light and transmission electron microscopy study].
To perform a morphometric and ultrastructural analysis of the various cellular components that constitutes the endometrial epithelium during the implantation window. Endometrial biopsies of six patients in ageing to procreate were realized during the implantation window and analyzed using light and transmission electron microscopy (TEM). During the implantation window, four endometrial cell types are identified in distinct proportions: microvilli-rich cells, pinopode cells, ciliated cells and others without apical differentiation. We highlighted important differences between surface and glandular epitheliums. Pinopode cells are present in all biopsies; they are more frequent in glands than surface. Their maximum expression in the glandular epithelium is at the day 20 and in the surface epithelium at the day 22. The pinopodes are present since day 19, they appeared fully developed with a maximum at day 22. Using TEM for ultrastructural analysis, we showed images of endocytosis and numerous secretory vesicles in epithelial cells of the endometrium. Their plasmic membrane present apical differentiations in the form of microvilli covered with a very developed cell coat indicating a high activity of exchange with the extracellular compartment. The endometrial cells exhibit extensive signs of communication between neighboring cells appeared to be preserved. Our data suggest each cell type and each cell structure as a very precise function in order to prepare the endometrium to be receptive.


The role of vagal innervation on the early development of postoperative ileus in mice.
Postoperative ileus (POI) involves an intestinal inflammatory response that is modulated by afferent and efferent vagal activation. We aimed to identify the potential influence of the vagus nerve on POI by tracking central vagal activation and its role for peripheral inflammatory changes during the early hours after surgery. C57BL6 mice were vagotomized (V) 3-4 days prior to experiments, while control animals received sham vagotomy (SV). Subgroups underwent either laparotomy (sham operation; S-POI) or laparotomy followed by standardized small bowel manipulation to induce postoperative ileus (POI). Three hours and 9 h later, respectively, a jejunal segment was harvested and infiltration of inflammatory cells in intestinal muscularis was evaluated by fluorescein isothiocyanate (FITC) avidin and myeloperoxidase (MPO) staining. Moreover, the brain stem was harvested, and central nervous activation was investigated by Fos immunochemistry in both the nucleus of the solitary tract (NTS) and the area postrema (AP). Data are presented as mean ± SEM, and a p < 0.05 was considered statistically significant. Three hour experiments revealed no significant differences between all experimental groups, except MPO staining: 3 h after abdominal surgery, there were significantly more MPO-positive cells in vagotomized S-POI animals compared to sham-vagotomized S-POI animals (26.7 ± 7.1 vs. 5.1 ± 2.4, p < 0.01). Nine hour postoperatively intramuscular mast cells (IMMC) were significantly decreased in the intestinal muscularis of V/POI animals compared to SV/POI animals (1.5 ± 0.3 vs. 5.9 ± 0.2, p < 0.05), while MPO-positive cells were increased in V/POI animals compared to SV/POI animals (713.2 ± 99.4 vs. 46.9 ± 5.8, p < 0.05). There were less Fos-positive cells in the NTS of V/POI animals compared to SV/POI animals (64.7 ± 7.8 vs. 132.8 ± 23.9, p < 0.05) and more Fos-positive cells in the AP of V/POI animals compared to SV/POI animals 9 h postoperatively (38.0 ± 2.0 vs. 13.7 ± 0.9, p < 0.001). Afferent nerve signaling to the central nervous system during the development of early POI seems to be mediated mainly via the vagus nerve and to a lesser degree via systemic circulation. During the early hours of POI, the intestinal immune response may be attenuated by vagal modulation, suggesting interactions between the central nervous system and the intestine.


Anticonvulsant drug actions on in vitro and in vivo levels of cyclic AMP in the mouse brain.
Injections of pentylenetetrazol to mice produced a rise in steady state levels of cyclic AMP in the cerebrum and cerebellum subsequent to sacrifice by focused microwave irradiation. One hour pretreatment with anticonvulsant drugs--phenytoin, phenobarbital, carbamazepine, clonazepam, and diazepam--prevented this pentylenetetrazol-induced rise in cyclic AMP. Anticonvulsant agents which alone depressed steady state levels of cyclic AMP were phenytoin and carbamazepine in the cerebral cortex and carbamazepine in the cerebellum while elevations in the cyclic nucleotide were evoked by clonazepam in the cerebrum and cerebellum or diazepam and phenytoin in the cerebellum. Under in vitro conditions, in which incubated tissue slices of mouse cerebral cortex were used, the stimulation of cyclic AMP by norepinephrine was blocked by carbamazepine greater than phenobarbital greater than phenytoin. Inhibition of adenosine-induced accumulation of cyclic AMP was observed with phenobarbital greater than carbamazepine greater than phenytoin. Clonazepam enhanced this response to adenosine. Ouabain stimulation of cyclic AMP was prevented by carbamazepine, phenytoin greater than clonazepam greater than phenobarbital greater than diazepam. Only the highest concentrations (0.5 mM) of phenytoin, phenobarbital, and carbamazepine reduced the action of KCl on cyclic AMP elevation. Clonazepam and diazepam elevated the basal levels of the cyclic nucleotide.


Variation of salivary calcium, phosphate and buffering capacity in adolescents.
Calcium, phosphate and buffering capacity were measured in children's (n=43) unstimulated saliva between September 1990 and June 1991 inclusive. Saliva samples were collected in the afternoon, once a month, on 10 consecutive occasions. Buffering capacity was assessed immediately after sample collection using the Dentobuff strip method. The remainder of the saliva sample was then stored at -18 degrees C and, after thawing, total calcium and inorganic phosphate were measured. The intra-individual variation of buffering capacity over time was statistically significant (Friedman two-way ANOVA, p < 0.001). The intra-individual variability of salivary calcium was also statistically significant (repeated-measures ANOVA, p < 0.001). However, no evidence of a statistically significant variation in phosphate was observed. It is concluded that a combination of flow-rate fluctuation over time and the methods used to assess salivary constituents might have contributed to this variability.


HDAC inhibition promotes both initial consolidation and reconsolidation of spatial memory in mice.
Accumulating evidence suggests a critical role for epigenetic regulations in long term memory (LTM) formation. Among them, post-translational modifications of proteins, as histone acetylation, are an important regulator of chromatin remodelling and gene transcription. While the implication of histone acetylation in memory consolidation is widely accepted, less is known about its role in memory reconsolidation i.e. during memory restabilization after its reactivation. In the present study, we investigated the role of histone acetylation during the initial consolidation and the reconsolidation of spatial memory, using a weak massed learning procedure in the Morris water maze paradigm in mice. Usually a weak learning is sufficient for short term memory (STM) formation, but insufficient to upgrade STM to LTM. We found that promoting histone acetylation through intra-hippocampal infusion of a class I selective histone deacetylase (HDAC) inhibitor immediately after a subthreshold spatial learning improved LTM but not STM retention. More importantly, inhibiting HDAC activity after the reactivation of a weak memory promoted specifically LTM reconsolidation without affecting post-reactivation STM. These findings argue in favour of an important role for histone acetylation in memory consolidation, and more particularly during the reconsolidation of spatial memory in mice.


Investigating the microstructure of high-calcium fly ash-based alkali-activated material for aqueous Zn sorption.
The performance of adsorbents prepared by alkali activation of high calcium fly ash was investigated for removing aqueous Zn. Two formulations involving the use of NaOH and Na2SiO3 activating solutions were used to prepare the adsorbents that feature different microstructural characteristics. The Zn sorption data indicates a sorption process that is controlled by both chemisorption and intra-particle diffusion. The Na2SiO3-activated material displayed higher sorption rates compared to the NaOH-activated material. The sorption kinetics show strong dependence on the microstructures of the adsorbents, wherein the Na2SiO3-activated material featuring higher contents of amorphous phases (96 %mass) in the hydrated phase assemblage, with attendant improved porosity and surface area, performed better than the NaOH-activated material (86 %mass amorphous phases) which showed higher degree of crystallinity and coarse morphology. The Na2SiO3-activated material exhibited 100% Zn removal efficiency within the first 5 min in all studied initial adsorbate concentrations(corresponding to sorption capacity of up to 200 mg/g), while the NaOH-activated analogue tends to lag, reaching 99.99% Zn removal efficiency after about 240 min in most cases. The two formulations were also examined with thermodynamic modeling and the results agree with experimental data in indicating that the use of alkali-silicate activating solution is most suitable for converting high calcium fly ash into efficient adsorbent for removing aqueous heavy metals.


The Arabidopsis clock: time for an about-face?
Three recent studies have altered thinking on the role of TIMING OF CAB EXPRESSION 1 (TOC1), a core element in the plant circadian oscillator.


The role of therapist support on effectiveness of an internet-based modular self-help intervention for adjustment disorder: a randomized controlled trial.
Adjustment disorder is among the most often diagnosed mental health disorders. Still, there is a lack of specific interventions available for adjustment disorder. The aim of this study was to test if an internet-based self-help intervention for adjustment disorder could be effective without therapist involvement. A parallel group randomized controlled trial design was used to test the effectiveness of the Brief Adjustment Disorder Intervention (BADI) - an internet-based intervention for adjustment disorder. In total 1077 participants were randomized into two conditions: BADI intervention and BADI intervention with therapist support. The main outcome measures were symptoms of adjustment disorder and well-being. Pre-intervention to post-intervention adjustment disorder effect size for the BADI intervention group was d = 0.64, and for the BADI with therapist support group the effect size was d = 0.53. The present study supported the effectiveness of the BADI intervention. Our findings also indicated that adding therapist support to the standard BADI intervention did not significantly improve the outcomes.


Intratumoral genetic and immune microenvironmental heterogeneity in T4N0M0 (diameter ≥ 7 cm) non-small cell lung cancers.
Starting with low metastatic capability, T4N0M0 (diameter ≥ 7 cm) non-small cell lung cancers (NSCLCs) constitute a unique tumor subset, as with a large tumor size but no regional or distant metastases. We systematically investigated intratumoral heterogeneity, clonal structure, chromosomal instability (CIN), and immune microenvironment in T4N0M0 (≥7 cm) NSCLCs. Whole-exome sequencing, RNA sequencing, and multiplex immunohistochemistry (mIHC) staining were conducted to analyze 24 spatially segregated tumor samples from eight patients who were pathologically diagnosed with T4N0M0 (diameter ≥ 7 cm) NSCLCs. The adjacent normal tissues and peripheral blood served as controls. In total, 35.2% of mutations and 91.1% of somatic copy number alterations were classified as subclonal events, which exhibited widespread genetic intratumoral heterogeneity. In contrast, a low degree of CIN was observed. None of the patients had genome doubling. The burden of loss of heterozygosity, aneuploidy, and the genome instability index of these tumors were significantly lower than those in the TRACERx cohort. Expression profiles revealed significantly upregulated expression of cell division-related signals and the G2/M checkpoint pathway. In addition, a similar expression pattern of the immune microenvironment was observed in different regions of the tumor, which was confirmed by mIHC profiles. Our study indicates the presence of intratumoral genetic heterogeneity and immune microenvironmental heterogeneity features in T4N0M0 NSCLCs, and the low degree of CIN may be related to the low metastatic capability.


Utilization and Outcomes of Inpatient Urological Care at Safety Net Hospitals.
Because proposed funding cuts in the Patient Protection and Affordable Care Act may impact care for urological patients at safety net hospitals, we examined the use, outcomes and costs of inpatient urological surgery at safety net vs nonsafety net facilities prior to health care reform. Using the Nationwide Inpatient Sample we performed a retrospective cohort study of patients who underwent inpatient urological surgeries from 2007 through 2011. We defined the safety net burden of each hospital based on the proportion of Medicaid and self-pay discharges. We examined the distribution of urological procedures performed and compared in-hospital mortality, prolonged length of stay and costs in the highest quartile of burden (safety net) vs the lowest quartile (nonsafety net). The distribution of urological procedures differed by safety net status with less benign prostate surgery (9.1% safety net vs 11.4% nonsafety net) and major cancer surgery (26.9% vs 34.3%), and more reconstructive surgery (8.1% vs 5.5%) at safety net facilities (p <0.001). Higher mortality at safety net hospitals was seen for nephrectomy (OR 1.68, 95% CI 1.15-2.45) and transurethral resection of the prostate (OR 2.17, 95% CI 1.22-3.87). Patients in safety net hospitals demonstrated greater prolonged length of stay after endoscopic stone surgery (OR 1.20, 95% CI 1.01-1.41). Costs were similar across procedures except for radical prostatectomy and cystectomy. For these procedures the average admission was more expensive at nonsafety net facilities (prostatectomy $11,457 vs $9,610 and cystectomy $27,875 vs $24,048, each p <0.02). Reductions in funding to safety net hospitals with health care reform could adversely impact access to care for patients with a broad range of urological conditions, potentially exacerbating existing disparities for vulnerable populations served by these facilities.


TRPM7 promotes the epithelial-mesenchymal transition in ovarian cancer through the calcium-related PI3K / AKT oncogenic signaling.
The epithelial-mesenchymal transition (EMT) is crucial for metastasis and positively regulated by calcium-related signaling. The melastatin-related transient receptor potential 7 (TRPM7) regulates a non-selective cation channel and promotes cancer metastasis. However, the mechanisms underlying the action of TRPM7 in ovarian cancer are unclear. The expression of TRPM7 and EMT markers (Vimentin, N-cadherin, Twist and E-cadherin) in ovarian cancer samples was detected. TRPM7was knockdown by shRNA in Ovarian cancer cell lines to examine calcium [Ca2+]i, EMT markers and PI3K/AKT markers. Various cellular assays, such as invasion and migration, were performed in vitro, and further confirmed in vivo. TRPM7 expression is negatively correlated with E-cadherin, but positively with N-cadherin, Vimentin and Twist expression in ovarian cancer samples. TRPM7 depletion inhibited the migration and invasion in SKOV3 and OVCAR3 cells. In addition, TRPM7 silencing decreased the lung metastasis of SKOV3 tumors and prolonged the survival of tumor-bearing mice. Similar to that of TRPM7 silencing, treatment with MK886, a potent 5-lipoxygenase inhibitor to reduce TRPM7 expression, and/or BAPTA-AM, an intracellular calcium chelator, significantly mitigated the Epidermal growth factor (EGF) or Insulin-like growth factors (IGF)-stimulated migration, invasion, and the EMT in ovarian cancer cells by decreasing the levels of intracellular calcium [Ca2+]i. Furthermore, treatment with LY2904002, a PI3K inhibitor, also inhibited the migration, invasion, and treatment with both LY2904002 and BAPTA-AM further enhanced their inhibition in ovarian cancer cells. Moreover, treatment with BAPTA-AM mitigated the IGF-stimulated migration, invasion, particularly in TRPM7-silenced ovarian cancer cells. Finally, TRPM7 silencing attenuated the PI3K/AKT activation, which was enhanced by BAPTA-AM, MK886 or LY2904002 treatment in ovarian cancer cells. TRPM7 silencing inhibited the EMT and metastasis of ovarian cancer by attenuating the calcium-related PI3k/AKT activation. Our findings suggest that TRPM7 may be a therapeutic target for intervention of ovarian cancer.


Neuroprotective potential of antihyperglycemic drug metformin in streptozocin-induced rat model of sporadic Alzheimer's disease.
The earliest hallmarks of sporadic Alzheimer's disease (sAD) are impaired glucose metabolism, chronic neuroinflammation, diminished synaptic plasticity and subsequent cognitive decline. The safest antidiabetic drug metformin has shown both glucose metabolism-improving and cognition-enhancing action in type 2 diabetes patients and diabetic model animals. However, metformin has not been previously studied in intracerebroventricular streptozocin (STZ)-induced model of sAD. Therefore, our aim was to assess the preventive action of metformin in sAD model-rats. Firstly, the actions of metformin (75 and 100 mg/kg) on cognitive functions and sociability were examined. Secondly, we wanted to identify whether behavioral effects of metformin were provided via its action on brain glucose transport, neuronal/glial uptake and metabolism. Thirdly, the effects of metformin on neuroinflammation, acetylcholine esterase density and activity, as well as on synaptic plasticity were determined. Our results showed that metformin reversed STZ-induced impairments in spatial learning/memory performance and sociability, coinciding with normalization of brain glucose transport, uptake and metabolism. Microgliosis and astrogliosis were ameliorated by metformin in sAD model rats. Metformin also preserved hippocampal synaptic plasticity and normalized acetylcholine cleavage in the cortical and hippocampal tissues, as well as inhibited acetylcholine esterase activity in vitro. These data indicate the promise of further research of metformin in early brain pathologies to stop neurodegenerative before severe cognitive decline occurs.


Prevalence and determinants of smoking behavior among physicians in emergency department: A national cross-sectional study in China.
To understand the current status of smoking behavior among emergency physicians in China and to explore its determinants. The emergency department is considered a more appropriate setting for tobacco interventions. However, the smoking behavior of emergency physicians can reduce the effectiveness of interventions for patient smoking behavior. From July to August 2018, we conducted a structured online questionnaire among Chinese emergency medicine physicians. We used descriptive analysis with binary logistic regression to analyze the current smoking status of Chinese emergency physicians and its determinants. A total of 10,457 emergency physicians were included in this study. The prevalence of smoking among physicians was 25.35% (with 34.15 and 1.59% among male and female physicians, respectively). Results of logistic regression showed that postgraduate education (OR = 0.52, 95% CI: 0.41-0.66), chief-level title (OR = 0.79, 95% CI: 0.65-0.97), and regular exercise habits (OR = 0.83, 95% CI: 0.76-0.92) were associated with a lower risk of smoking behavior. However, being over 50 years old (OR = 1.71, 95% CI: 1.29-2.27), being fixed-term (OR = 1.25, 95% CI: 1.10-1.42), and having depressive symptoms (OR = 1.43, 95% CI: 1.28-1.61) were associated with a higher risk of smoking. The prevalence of smoking behavior among emergency physicians in China is high. Hospital management could reduce the incidence of smoking behavior among emergency physicians by strengthening smoking cessation training, paying attention to physicians' psychological health, reducing pressure on physicians in fixed-term positions, and encouraging physicians to develop regular exercise habits.


Liver Stiffness-Based Strategies Predict Absence of Variceal Bleeding in Cirrhotic Hepatitis C Virus-Infected Patients With and Without Human Immunodeficiency Virus Coinfection After Sustained Virological Response.
In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.


The effects of adenosine triphosphate and related purines on arterial resistance vessels in vitro and in vivo.
The distribution of P2-purinoceptors in pre-capillary resistance vessels was studied in vitro, using Krebs perfused rabbit ears and in vivo, in autoperfused hindquarters, intestinal and renal vasculatures of pentobarbitone anaesthetised cats. ATP (10(-10)-10(-6) mol i.a.) caused dose-dependent vasodilatation which, in the rabbit ear, was antagonised by reactive blue 2 (10(-5)-10(-4) M). At the highest concentration of reactive blue 2, ATP responses were reversed and a dose-dependent vasoconstriction was seen. Reactive blue 2, also reduced the vasodilator responses to carbachol and to a lesser extent papaverine which suggests that the antagonist has limited selectivity. The rank order of potency of ATP analogues as vasodilators, 2-methylthio ATP greater than ADP greater than ATP greater than alpha,beta-methylene and beta,gamma-methylene ATP, suggests P2y purinoceptors are involved. The selective P2x-purinoceptor agonist, alpha,beta-methylene ATP, caused pronounced vasoconstriction in the rabbit ear and cat intestinal vasculature which was not antagonised by phenoxybenzamine. In contrast, alpha,beta-methylene ATP had little effect in the autoperfused hindquarters and renal vasculatures suggesting a very heterogeneous distribution of P2x-purinoceptors in the cat. The results are consistent with the proposal that two distinct types of P2-purinoceptors are present on blood vessels.


Expression polymerase chain reaction for the in vitro synthesis and epitope mapping of autoantigen. Application to the human thyrotropin receptor.
The clinical applicability of a newly described polymerase chain reaction directed protein expression system was assessed for the in vitro synthesis and partial epitope mapping of large radiolabeled human thyrotropin receptor (hTSH-R) protein segments. PCR amplification of targeted regions within the hTSH-R cDNA followed by in vitro transcription and translation permitted rapid synthesis of protein segments ranging in size from 18 to 62 kDa. Initial epitope mapping was directed at a 52 amino acid segment unique to the hTSH-R compared to otherwise homologous glycoprotein hormone receptors. Sera from Graves' disease patients known to have autoantibodies against the hTSH-R were used to immunoprecipitate two protein fragments differing only by the presence of the unique region in the larger fragment (E5) but not in the smaller fragment (E4). Dense precipitation bands were obtained using Graves' sera to immunoprecipitate E5 whereas little or no specific immunoprecipitation of E4 occurred. Normal sera gave only weak immunoprecipitation bands of E5. The technique provides significant advantages over conventional cloning methods and should have general applicability in the study of other protein targets of autoimmune disease.


Characteristics of denitrification activity, functional genes, and denitrifying community composition in the composting process of kitchen and garden waste.
N2O can be easily produced during the co-composting of kitchen waste (KW) and garden waste (GW). This study investigated the effects of the co-composting of KW and GW at different ratios (1:2, 1:1.5, 1:1, and 1.5:1) on the denitrifying activities, functional genes, and community composition of denitrifiers. The results showed that the denitrification activity of KW and GW at a 1:2 ratio was the lowest. The gene abundances of nirS, nirK, nosZI, and nosZII were high on days 12 and 28 under the four different ratios. Network analysis demonstrated that nosZ-type denitrifiers could construct a complex and reciprocal bacterial network to promote the reduction of N2O to N2. Mantel test results revealed that nirS-, nirK-, nosZI-, and nosZII-type denitrifiers were significantly positively correlated with pH, C/N, and moisture content. These findings demonstrated that composting with appropriate proportions of KW and GW could reduce N2O emissions caused by denitrification.


Dissecting aggressive B-cell lymphoma through genomic analysis - What is clinically relevant?
The aggressive B-cell lymphomas are a diverse collection of cancers grouped together based on clinical behavior and derivation from B lymphocytes. Genomic analyses on these tumours are now translating into improved classification systems and identification of underpinning targetable biology. Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme. Subsequently, gene expression profiling identified molecular subgroups within the most common lymphoma, diffuse large B-cell lymphoma (DLBCL): activated B-cell-like and germinal centre B-cell-like. Finally, next generation sequencing has revealed a modest number of frequently mutated genes and a long list of infrequent mutations. The mutational landscapes involve diverse genes associated with dysregulated signalling, epigenetic modification, blockade of cellular differentiation, and immune evasion. These mutational "signatures" are enriched in the different aggressive lymphoma subtypes impacting phenotypes and identifying therapeutic targets. Challenges to implementing genomic assays into clinical practice remain.


TMEM126A is a mitochondrial located mRNA (MLR) protein of the mitochondrial inner membrane.
Hereditary optic neuropathies (HONs) are a heterogeneous group of disorders that affect retinal ganglion cells (RGCs) and axons that form the optic nerve. Leber's Hereditary Optic Neuropathy and the autosomal dominant optic atrophy related to OPA1 mutations are the most common forms. Nonsyndromic autosomal recessive optic neuropathies are rare and their existence has been long debated. We recently identified the first gene responsible for these conditions, TMEM126A. This gene is highly expressed in retinal cellular compartments enriched in mitochondria and supposed to encode a mitochondrial transmembrane protein of unknown function. A specific polyclonal antibody targeting the TMEM126A protein has been generated. Quantitative fluorescent in situ hybridization, cellular fractionation, mitochondrial membrane association study, mitochondrial sub compartmentalization analysis by both proteolysis assays and transmission electron microscopy, and expression analysis of truncated TMEM126A constructs by immunofluorescence confocal microscopy were carried out. TMEM126A mRNAs are strongly enriched in the vicinity of mitochondria and encode an inner mitochondrial membrane associated cristae protein. Moreover, the second transmembrane domain of TMEM126A is required for its mitochondrial localization. TMEM126A is a mitochondrial located mRNA (MLR) that may be translated in the mitochondrial surface and the protein is subsequently imported to the inner membrane. These data constitute the first step toward a better understanding of the mechanism of action of TMEM126A in RGCs and support the importance of mitochondrial dysfunction in the pathogenesis of HON. Local translation of nuclearly encoded mitochondrial mRNAs might be a mechanism for rapid onsite supply of mitochondrial membrane proteins.


Size exclusion chromatography with evaporative light scattering detection as a method for speciation analysis of polydimethylsiloxanes. III. Identification and determination of dimeticone and simeticone in pharmaceutical formulations.
The pharmaceutical industry is one of the more important sectors for the use of polydimethylsiloxanes (PDMS), which belong to the organosilicon polymers. In drugs for internal use, they are used as an active pharmaceutical ingredient (API) called dimeticone or simeticone. Due to their specific chemical nature, PDMS can have different degrees of polymerization, which determine the molecular weight and viscosity. The Pharmacopoeial monographs for dimeticone and simeticone, only give the permitted polymerization and viscosity range. It is, however, essential to know also the degree of polymerization or the specific molecular weight of PDMS that are present in pharmaceutical formulations. In the literature there is information about the impact of particle size, and thus molecular weight, on the toxicity, absorption and migration in living organisms. This study focused on the use of a developed method - the exclusion chromatography with evaporative light scattering detector (SEC-ELSD) - for identification and determination of dimeticone and simeticone in various pharmaceutical formulations. The method had a high degree of specificity and was suitable for speciation analysis of these polymers. So far the developed method has not been used in the control of medicinal products containing dimeticone or simeticone.


Element-selective imaging of atomic columns in a crystal using STEM and EELS.
Microstructure characterization has become indispensable to the study of complex materials, such as strongly correlated oxides, and can obtain useful information about the origin of their physical properties. Although atomically resolved measurements have long been possible, an important goal in microstructure characterization is to achieve element-selective imaging at atomic resolution. A combination of scanning transmission electron microscopy (STEM) and electron energy-loss spectroscopy (EELS) is a promising technique for atomic-column analysis. However, two-dimensional analysis has not yet been performed owing to several difficulties, such as delocalization in inelastic scattering or instrumentation instabilities. Here we demonstrate atomic-column imaging of a crystal specimen using localized inelastic scattering and a stabilized scanning transmission electron microscope. The atomic columns of La, Mn and O in the layered manganite La1.2Sr1.8Mn2O7 are visualized as two-dimensional images.


Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection.
Triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxicillin or nitroimidazole derivatives are the present gold standards for cure of Helicobacter pylori infection. However, primary resistance to either clarithromycin or nitroimidazole derivatives is increasing and alternative therapies are needed. To determine the efficacy and safety of three regimens consisting of amoxicillin and tetracycline or doxycycline combined with either lansoprazole or ranitidine bismuth citrate. Two hundred and seventy H. pylori infected patients were randomly given one of the following treatments: amoxicillin 1 g twice a day (b.i.d.) plus tetracycline 500 mg four times a day (q.i.d.) with either lansoprazole 30 mg b.i.d. (group LAT) or ranitidine bismuth citrate 400 mg b.i.d. (group RBCAT) for 7 days and amoxicillin 1 g b.i.d. plus doxycycline 100 mg b.i.d. and lansoprazole 30 mg b.i.d. for 14 days (group LAD). Eradication rate was assessed by UBT at 4-6 weeks after therapy. The three groups (LAT, RBCAT, and LAD) of patients achieved eradication rates of 35% (25-45), 20% (12-29) and 36% (25-46), respectively, on intention-to-treat analysis. Patient compliance was optimal and side-effects minimal in all three groups. Although the amoxicillin/tetracycline combination is attractive (inexpensive, safe, and with low primary resistance rate), it can not be recommended for H. pylori eradication.


[Computerized tomography in the diagnosis of space-occupying gynecological processes. 2: examination technic and normal anatomy of the female pelvis in CT scans].
Differentiation of the organs in the small pelvis by computed tomography is often difficult, because of the small differences of density. General contrasting the bowel, intravenous injection of opaque matter and tamponing the vagina can facilitate the identification and estimation of pathological processes of female genitals. Presumption of any findings is the exact knowledge of X-ray topography. Following the explanation of patient preparation and of examination technique the normal anatomy of female pelvis is demonstrated by seven scans.


Value of mechanical dyssynchrony as assessed by radionuclide ventriculography to predict the cardiac resynchronization therapy response.
To assess the value of mechanical dyssynchrony measured by equilibrium radionuclide angiography (ERNA) in predicting long-term outcome in cardiac resynchronization therapy (CRT) patients. We reviewed 146 ERNA studies performed in heart failure patients between 2001 and 2011 at our institution. Long-term follow-up focused on death from any cause or heart transplantation. Phase images were computed using the first harmonic Fourier transform. Intra-ventricular dyssynchrony was calculated as the delay between the earliest and most delayed 20% of the left ventricular (LV) (IntraV-20/80) and inter-ventricular dyssynchrony as the difference between LV- and right ventricular (RV)-mode phase angles (InterV). Eighty-three patients (57%) were implanted with a CRT device after ERNA. Median follow-up was 35 [21-50] months. Twenty-four events were observed during the first 41 months. Median baseline ERNA dyssynchrony values were 28 [3 to 46] degrees for intraV-20/80 and 9 [-6 to 24] degrees for interV. Comparing survival between CRT and non-CRT patients according to dyssynchrony status, log-rank tests showed no difference in survival in patients with no ERNA dyssynchrony (P = 0.34) while a significant difference was observed in ERNA patients with high level of mechanical dyssynchrony (P = 0.004). ERNA mechanical dyssynchrony could be of value in CRT patient selection.


[Effect of cation concentration and medium pH on the distance between 2 lipid bilayers in the contact zone].
Dependence of the distance between contacting bilayer lipid membranes on the concentration of mono-and bivalent cations and medium pH has been measured by an optimcal method. It has been show that the presence of cations in the medium decreases the equilibrium distance between contacting membranes, the effect being more pronounced for bivalent Ca.


Review of self-efficacy assessment scales for geriatric patients with urinary incontinence.
Urinary incontinence is a common condition in the elderly, which can be improved with rehabilitation. However, compliance with the rehabilitation regimen is influenced by the level of self-efficacy. Self-efficacy of elderly patients in dealing with urinary incontinence can be clinically assessed and understood by using a suitable scale, to implement specific improvement measures. At present, the tools used for assessing the self-efficacy of elderly patients with urinary incontinence include the General Self-Efficacy Scale (GSES), the Pelvic Floor Muscle Self-efficacy Scale, the Geriatric Self-efficacy Index for Urinary Incontinence, and the Yoga Self-Efficacy Scale. Most of these tools are suitable for female patients with urinary incontinence, but lack relevance to the disease characteristics of geriatric patients. In this study, we reviewed the self-efficacy assessment tools for geriatric patients with urinary incontinence, to provide a reference for related research. It is important to accurately assess the self-efficacy of patients with geriatric UI to effectively enhance their level of self-efficacy, so that patients with geriatric UI can avail early help and quickly reintegrate with family and society.


Association of nativity with survival among adults with hepatocellular carcinoma.
Immigrants comprise a considerable proportion of those diagnosed with hepatocellular carcinoma (HCC) in the United States. Nativity or birthplace affects incidence and risk factors for HCC, but little is known about its influence on survival after diagnosis. We identified 51 533 adults with HCC with available birthplace in the California Cancer Registry between 1988 and 2017. HCC cases were categorized as foreign born or US born and stratified by mutually exclusive race and ethnicity groups. Primary outcome was all-cause mortality. Race and ethnicity-specific Cox regression propensity score-weighted models evaluated the relationship between nativity and death as well as region of birth among foreign-born patients. A total of 40% of all HCC cases were foreign born, and 92.2%, 45.2%, 9.1%, and 5.8% of Asian/Pacific Islander (API), Hispanic, White, and Black patients were foreign born, respectively. Five-year survival rates were higher in foreign-born patients compared with US-born patients: 12.9% vs 9.6% for White patients, 11.7% vs 9.8% for Hispanic patients, 12.8% vs 8.1% for Black patients, and 16.4% vs 12.4% for API patients. Nativity was associated with survival, with better survival in foreign-born patients: White patients: hazard ratio (HR) = 0.86 (95% confidence interval [CI] = 0.81 to 0.90), Hispanic patients: HR = 0.90 (95% CI = 0.86 to 0.93), Black patients: HR = 0.89 (95% CI = 0.76 to 1.05), and API patients: HR = 0.94 (95% CI = 0.88 to 1.00). Among foreign-born patients, lower mortality was observed in those from Central and South America compared with Mexico for Hispanic patients, East Asia compared with Southeast Asia for API patients, and East Europe and Greater Middle East compared with West/South/North Europe for White patients. Foreign-born patients with HCC have better survival than US-born patients. Further investigation into the mechanisms of this survival disparity by nativity is needed.


Refractory Impella Suction Alarms in the Setting of Extracorporeal Membrane Oxygenation.
Cardiogenic shock is an uncommon but serious complication of acute myocardial infarction. Temporary mechanical circulatory support devices are being used more often in this setting, and physicians are required to be familiar with their complications. Although veno-arterial extracorporeal membrane oxygenation increases after loading, an Impella device can be inserted to unload the left ventricle and decrease its oxygen consumption. Here, we present an uncommon cause of a refractory Impella suction alarm, which was related to the migration of the venous extracorporeal membrane oxygenation cannula into the left atrium.


Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor.
Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation.


TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848).
TLR ligands that mimic pathogen associated molecular patterns and activate immune cells via Toll-like receptors (TLRs) are being developed for use in humans as therapy against a variety of diseases as well as vaccine adjuvants. These include imidazoquinoline compounds such as Imiquimod and Resiquimod (R-848) that bind to TLR7 and 8, as well as CpG oligodeoxynucleotides (CpG ODN) that bind to TLR9. This study was aimed at comparing CpG ODN and R-848 for their potential use as vaccine adjuvants and to determine whether there are additive or synergistic effects when they are used together. Using HBsAg as a model antigen in mice, we show CpG ODN to be superior to R-848 for augmenting both humoral and cell mediated immune responses.


Current insights into the role of citrullination in thrombosis.
Protein citrullination is a post-translational modification of arginine that controls a diverse array of cellular processes, including gene regulation, protein stability, and neutrophil extracellular trap (NET) formation. Histone citrullination promotes chromatin decondensation and NET formation, a pro-inflammatory form of cell death that is aberrantly increased in numerous immune disorders. This review will provide insights into NETosis and how this novel form of cell death contributes to inflammatory diseases, with a particular emphasis on its role in thrombosis. We will also discuss recent efforts to develop PAD-specific inhibitors.


Complete genome analysis and biological characterization of a novel phage vB_CP_qdyz_P5 with lytic activity against Clostridium perfringens.
Clostridium perfringens, a common foodborne pathogen, exhibit high-stress resistance. The prevailing reliance on antibiotics in the farming industry for its prevention and control has led to increasing concerns over antibiotic residue and bacterial resistance. Bacteriophages that possess specific lytic activity against C. perfringens are of significant interest. Here, a novel C. perfringens phage, named vB_CP_qdyz_P5, was isolated and characterized. The phage displayed high stability at temperatures below 70 °C and pH levels ranging from 4 to 12. Genome analysis revealed that vB_CP_qdyz_P5 has a double-stand DNA of 18,888 bp with a G + C composition of 28.8%. Among the 27 identified opening reading frames (ORFs), eight were found to be functional genes. BLASTn analysis showed that vB_CP_qdyz_P5 is closely related to phage DCp1, with a genome homology coverage of 83%. Phylogenetic analysis indicated that vB_CP_qdyz_P5 may be a novel phage of the family Guelinviridae, Susfortunavirus. This study provides important preliminary information for further research on the potential use of vB_CP_qdyz_P5 in protecting against C. perfringens and maintaining intestinal health.


Targeted resequencing of 9p in acute lymphoblastic leukemia yields concordant results with array CGH and reveals novel genomic alterations.
Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparison with array comparative genomic hybridization (aCGH), and besides, to detect novel genetic anomalies. We found a high concordance of copy number variations (CNVs) as detected by next generation sequencing (NGS) and aCGH. By both methodologies, the recurrent deletion at CDKN2A/B locus was identified, whereas NGS revealed additional, small regions of CNVs, seen more frequently in adult patients, while aCGH was better at detecting larger CNVs. Also, by NGS, we detected novel structural variations, novel SNVs and small insertion/deletion variants. Our results show that NGS, in addition to detecting mutations and other genetic aberrations, can be used to study CNVs.


Polyclonal activation of B cells during rubella infection.
Intensive spontaneous production of IgG by peripheral blood lymphocytes in vitro is detected at the onset of rash in patients with rubella virus infection. The IgG synthesized consists not only of antibodies against rubella virus specific antigens but also of antibodies to unrelated viruses.


Solitary juxtacortical neurofibroma of the humerus.
A neurofibroma as a discrete, superficial tumor of a long bone has been described only once in the world literature. We report the radiologic findings of a case of a juxtacortical neurofibroma.


[Churg-Strauss syndrome--report of four cases].
Four subsequent cases of Churg-Strauss syndrome were presented. The patients fulfilled criteria of the syndrome developed by American College of Rheumatology. They were treated with combination of systemic corticosteroids and cyclophosphamide, one patient was additionally treated with plasmapheresis. In all four cases complete remission of the disease was achieved.


Effectiveness of aerobic and resistance exercise in cancer survivors with depression: A systematic review and meta-analysis of randomized controlled trials.
AE and RE have been found to be effective for depressive symptoms. However, a systematic review and meta-analysis of studies examining the effectiveness of exercises for cancer survivors with depressive symptoms is lacking. We aimed to synthesize studies assessing AE and RE's efficacy and examine their effects on depressive symptoms among cancer survivors using meta-analyses. This review was registered on the PROSPERO website with ID CRD42023389760. A systematic literature search was conducted in the four databases. Data were synthesized using a random-effect model to analyze the impact of AE and RE on depressive symptoms at posttreatment and in medium-term follow-up relative to the control group. Subgroup analyses were conducted to investigate which factors are relevant to greater or lesser effects of treating depressive symptoms among cancer survivors. 28 RCTs (2942 participants) were identified. Analyses of the between-group showed that AE and/or RE were effective in alleviating depressive symptoms among cancer survivors in immediate posttreatment (SMD = -0.16; 95% CI = -0.29 to -0.03; p = 0.02) but not in medium-term follow-up (SMD = -0.01; 95% CI = -0.57 to 0.55; p = 0.97). Subgroup analyses suggested that AE and exercise 3 times per week were significant moderators. AE and RE were feasible in mitigating depressive symptoms in cancer patients. Further studies are needed to examine if exercise is psychologically beneficial for patients with specific types of cancer.


Heterocyclic ring cleavage upon collision-induced dissociation of deprotonated 3-hydroxy-1,2,5-oxadiazoles (3-hydroxyfurazans).
A series of 4-substituted 3-hydroxyfurazans were subjected to electrospray ionization tandem mass spectrometry. At low collision energy, oxyisocyanate ([O=C=N-O](-), m/z 58) was formed as the predominant product ion from each deprotonated 3-hydroxyfurazan, indicating cleavage of the heterocyclic ring. The facile energetics of this characteristic fragmentation process was confirmed by density functional computations.


What is the role of the coronary care nurse? A review of the literature.
The role of the coronary care nurse has often been described based on anecdotal evidence. However in a research conscious society it is vital that this important role is able to be defined using research findings. This paper explores the literature in order to describe this role in a research context. To review the literature to establish the contemporary role of the coronary care nurse. An electronic search of three healthcare databases to identify all journal articles published between 1990 and 2006. The review was focussed on all primary research or audit articles that discussed the roles of nurses working in coronary care units. Coronary care nurses are responsible for patient assessment and symptom management often using technology to achieve these goals. In addition they are able to develop therapeutic relationships with their patients and are in a prime position to provide vital physical and psychological care in both the critical and palliative stages of illness. Whilst no study has investigated the coronary care nursing role in its entirety the themes identified within many of the studies were consistent. Therefore the findings of this review are considered to be an accurate reflection of this role.


From Other Journals: A Review of Recent Articles in Pediatric Cardiology.
In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address the following: (1) transcatheter closure of sinus venous atrial septal defect which is feasible in adults with careful planning, (2) exercise echocardiography in children with hypertrophic cardiomyopathy which was found to be very helpful to identify low-risk patients when there is no gradient at rest or during exercise, (3) features of Fontan patients with normal exercise capacity who typically report more active life style and have less complications during the post-Fontan admissions, (4) the natural history of Anderson-Tawil syndrome which is characterized by high incidence of life-threatening arrhythmogenic events especially when there is history of syncope, ventricular tachycardia, or the use of amiodarone, (5) pulmonary artery banding in complete atrioventricular septal defects which were found to be a safe alternative to early complete repair and served as a bridge to biventricular repair with variable effect on common atrioventricular valve regurgitation and (6) tricuspid valve interventions (TVI) in patients undergoing pulmonary valve replacement (PVR) which further reduce tricuspid regurgitation beyond what is expected in PVR alone without increasing early complications or hospital length of stay.


Thriving locally in the global economy.
More and more small and midsize companies are joining corporate giants in striving to exploit international growth markets. At the same time, civic leaders worry about their communities' economic future in light of the impact of global forces on the operation and survival of business. How can communities retain local vitality yet still link their business to the global economy? Harvard professor Rosabeth Moss Kanter addresses that question in this classic HBR article, orginally published in 1995. To avoid a clash between international economic interests and local political interests, globalizing business must learn how to be responsive to the communities in which they operate, Kanter says. And communities must determine how to create a civic culture that will attract and retain footloose companies. The author surveyed five U.S. regions with direct connections to the global economy--Boston, Cleveland, Miami, Seattle, and the Spartanburg-Greenville region of South Carolina--to determine their business and civic leader's strategies for improving their constituent's quality of life. She identified ways in which the global economy can work locally by capitalizing on the resources that distinguish one place from another. Kanter argues that regions can invest in capabilities that connect their local populations to the global economy in one of three ways: as thinkers, makers, or traders. She points to the Spartanburg-Greenville region as a good example of a world-class makers, with its exceptional blue-collar workforce that has attracted more than 200 companies from 18 countries. The history of the economic development of this region is a lesson for those seeking to understand how to achieve world-class status and bring local residents into the world economy.


Active disturbance rejection control in steering by wire haptic systems.
This paper introduces a steering by wired haptic system based on disturbance rejection control techniques. High gain Generalized Proportional Integral (GPI) observers are considered for the estimation of tire and steering wheel dynamic disturbances. These disturbances are on line canceled to ensure tracking between the commanded steering wheel angle and the tire orientation angle. The estimated disturbances at the steering rack are feedback to the steering wheel to provide a haptic interface with the driver. The overall system behaves as a bilateral master-slave system. Very few sensors and minimum knowledge of the dynamic model are required. Experimental results are presented on a prototype platform that consists on: (1) half of the steering rack of a beetle VW vehicle, (2) a steering wheel.


Microscopic analysis of chromatin localization and dynamics in C. elegans.
During development, the genome undergoes drastic reorganization within the nuclear space. To determine tridimensional genome folding, genome-wide techniques (damID/Hi-C) can be applied using cell populations, but these have to be calibrated using microscopy and single-cell analysis of gene positioning. Moreover, the dynamic behavior of chromatin has to be assessed on living samples. Combining fast stereotypic development with easy genetics and microscopy, the nematode C. elegans has become a model of choice in recent years to study changes in nuclear organization during cell fate acquisition. Here we present two complementary techniques to evaluate nuclear positioning of genes either by fluorescence in situ hybridization in fixed samples or in living worm embryos using the GFP-lacI/lacO chromatin-tagging system.


Protective effect of Pai-Nong-San against AOM/DSS-induced CAC in mice through inhibiting the Wnt signaling pathway.
Pai-Nong-San (PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer (CAC) mouse model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4+ and CD8+ T cells, inhibiting the production of HIF-α, IL-6, and TNF-α, and promoting the expression of IL-4 and IFN-γ in colon tissues. Meanwhile, PNS improved the components of gut microbiota, as measured by the adjusted levels of Firmicutes, Bacteroidetes, Proteobacteria, and Lactobacillus. PNS down-regulated the protein expression of p-GSK-3β, β-catenin, and c-Myc, while up-regulating the GSK-3β and p-β-catenin in colon tissues of CAC mice. In conclusion, our results suggested that PNS exhibits protective effect on AOM/DSS-induced colon injury and alleviates the development of CAC through suppressing inflammation, improving gut microbiota, and inhibiting the Wnt signaling pathway.


JMJD4-demethylated RIG-I prevents hepatic steatosis and carcinogenesis.
Hepatocarcinogenesis is driven by necroinflammation or metabolic disorders, and the underlying mechanisms remain largely elusive. We previously found that retinoic acid-inducible gene-I (RIG-I), a sensor for recognizing RNA virus in innate immune cells, is mainly expressed by parenchymal hepatocytes in the liver. However, its roles in hepatocarcinogenesis are unknown, which is intensively investigated in this study. DEN-induced necroinflammation-driven hepatocarcinogenesis and STAM NASH-hepatocarcinogenesis were carried out in hepatocyte-specific RIG-I knockout mice. The post-translational modification of RIG-I was determined by mass spectrometry, and specific antibodies against methylated lysine sites and the RIG-I lysine mutant mice were constructed to identify the functions of RIG-I methylation. We interestingly found that DEN-induced hepatocarcinogenesis was enhanced, while NASH-induced hepatocarcinogenesis was suppressed by hepatocyte-specific RIG-I deficiency. Further, IL-6 decreased RIG-I expression in HCC progenitor cells (HcPCs), which then viciously promoted IL-6 effector signaling and drove HcPCs to fully established HCC. RIG-I expression was increased by HFD, which then enhanced cholesterol synthesis and steatosis, and the in-turn NASH and NASH-induced hepatocarcinogenesis. Mechanistically, RIG-I was constitutively mono-methylated at K18 and K146, and demethylase JMJD4-mediated RIG-I demethylation suppressed IL-6-STAT3 signaling. The constitutive methylated RIG-I associated with AMPKα to inhibit HMGCR phosphorylation, thus promoting HMGCR enzymatic activity and cholesterol synthesis. Clinically, RIG-I was decreased in human hepatic precancerous dysplastic nodules while increased in NAFLD livers, which were in accordance with the data in mouse models. Decreased RIG-I in HcPCs promotes necroinflammation-induced hepatocarcinogenesis, while increased constitutive methylated RIG-I enhances steatosis and NASH-induced hepatocarcinogenesis. JMJD4-demethylated RIG-I prevents both necroinflammation and NASH-induced hepatocarcinogenesis, which provides mechanistic insight and potential target for preventing HCC.


Identification of exposed surface glycoproteins of four human bladder carcinoma cell lines.
Three cell surface protein-specific methods were used to radiolabel the major glycoproteins of four human bladder carcinoma cell lines: The well-differentiated lines RT112 and TR4 and more anaplastic lines T24 and EJ. Five acidic glycoproteins iodinated in all lines by the lactoperoxidase/125I method were designated CP-175/5.8-6.0 (apparent molecular weight X 10(-3)/pl of iodoprotein), GP-155/5.0-5.3, GP-145/4.9-5.2, GP-130/4.8-5.5 and GP-110/4.9-5.3. Another iodinated glycoprotein, GP-200/5.5-6.0, was prominently labelled in RT112 and RT4 but was not detected in T24 or EJ. GP-200 as well as GP-175, GP-155 and GP-145 were not detected by the galactose oxidase/NaB(3H)4 method and were poorly labelled by the neuraminidase-galactose oxidase/NaB(3H)4 and NaIO4/NaB(3H)4 labelling methods. The major sialogalactoproteins identified in the four lines by the neuraminidase-galactose oxidase/NaB(3H)4 and NaIO4/NaB(3H)4 methods were GP-130, and a duplet of GP-90 and GP-80 which were poorly iodinated by lactoperoxidase/125I. The galactose oxidase/NaB(3H)4 reaction was increased by between 4- and 10-fold and many additional glycoproteins were labelled after neuraminidase treatment, indicating that the cell surface galactose and N-acetylgalactosamine residues of glycoproteins are highly sialylated. In cell lines RT112 and RT4 there was prominent labelling of very high molecular weight sialogalactoconjugates that was not present in extracts of T24 and EJ.


Synthetic prostaglandin1 analogue: in vitro studies on human neutrophils.
Prostaglandin (PG) E1 and chemically related compounds 15 alpha-11-deoxy-8-azaPGE1 and 15 epi-11-deoxy-8-azaPGE1 were examined in vitro for their capacity to modulate some physiological functions of human polymorphonuclear leukocytes (PMN). PGE1 was completely devoid of chemotactic activity and did not affect leukocyte phagocytosis. On the contrary, 15 alpha-11-deoxy-8-azaPGE1 showed a potent leukotactic activity. In addition, this synthetic substance significantly depressed the phagocytic activity and the concomitant NBT reduction by leukocytes. The analogue 15 epi-11-deoxy-8-azaPGE1 did not exert any of these effects. From these results it appeared that the substitution of the carbon-8 by the nitrogen and the lack of hydroxyl group at the position 11 into the PGE1 structure, make the compound active towards human neutrophils.


Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors.
Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.


Evolution of Olfactory Receptors Tuned to Mustard Oils in Herbivorous Drosophilidae.
The diversity of herbivorous insects is attributed to their propensity to specialize on toxic plants. In an evolutionary twist, toxins betray the identity of their bearers when herbivores coopt them as cues for host-plant finding, but the evolutionary mechanisms underlying this phenomenon are poorly understood. We focused on Scaptomyza flava, an herbivorous drosophilid specialized on isothiocyanate (ITC)-producing (Brassicales) plants, and identified Or67b paralogs that were triplicated as mustard-specific herbivory evolved. Using in vivo heterologous systems for the expression of olfactory receptors, we found that S. flava Or67bs, but not the homologs from microbe-feeding relatives, responded selectively to ITCs, each paralog detecting different ITC subsets. Consistent with this, S. flava was attracted to ITCs, as was Drosophila melanogaster expressing S. flava Or67b3 in the homologous Or67b olfactory circuit. ITCs were likely coopted as olfactory attractants through gene duplication and functional specialization (neofunctionalization and subfunctionalization) in S. flava, a recently derived herbivore.


Enantiomeric N-substituted phthalimides with excitatory amino acids protect zebrafish larvae against PTZ-induced seizures.
Epilepsy is a chronic neurological disease with high prevalence and adverse impacts on the quality of life of patients and caregivers. Up to one-third of individuals with epilepsy do not respond to current pharmacotherapy, underscoring the importance of identifying new molecules for epilepsy control. Thalidomide, the first synthetized phthalimide, is a neuroactive molecule with anti-seizure drug properties. The phthalimide group has been studied in some N-phthaloyl amino acids due to its pharmacological properties. Here we examine enantiomers of phthaloyl aspartate (R and S) and phthaloyl glutamate (R and S) for anti-seizure effects using zebrafish as a model. The zebrafish model is rapidly growing in use as a preclinical screening tool for drug discovery in epilepsy. Pentylenetetrazol (PTZ) exposure was used to produce convulsive behavior in 7- and 10-days post-fertilization (dpf) zebrafish larvae; these ages correspond to before and after the blood-brain-barrier (BBB) is fully developed. Larvae were pre-treated for 60 min with: control, valproic acid sodium salt (SVP) 3 mM, or one of two concentrations of N-phthaloyl-R-glutamic acid (R-TGLU; 100, 316 μM) prior to PTZ addition. R-TGLU modified the locomotor phenotype and protected against PTZ in 7 and 10 dpf larvae at 316 μM, suggesting it crossed the BBB. We next tested the per se and anticonvulsant effect of the glutamate and aspartate phthalimides were tested at 237.1 and 316 μM concentration in 10dpf zebrafish. The four tested molecules produced an anticonvulsant effect at 237.1 μM concentration, however the behavioral changes that they induce suggest that they might act by different mechanisms.


Actin-containing matrix associated with the plasma membrane of murine tumour and lymphoid cells.
A detergent-insoluble matrix has been isolated from murine tumour cell and lymphocyte plasma membranes. The major components of this matrix include actin and four additional proteins not previously identified as cytoskeletal proteins. Labelling studies indicate that the matrix is located on the inner face of the plasma membrane. A cell-surface glycoprotein, 5'-nucleotidase, remains associated with the isolated matrix.


Spatiotemporal multiplexed immunofluorescence imaging of living cells and tissues with bioorthogonal cycling of fluorescent probes.
Cells in complex organisms undergo frequent functional changes, but few methods allow comprehensive longitudinal profiling of living cells. Here we introduce scission-accelerated fluorophore exchange (SAFE), a method for multiplexed temporospatial imaging of living cells with immunofluorescence. SAFE uses a rapid bioorthogonal click chemistry to remove immunofluorescent signals from the surface of labeled cells, cycling the nanomolar-concentration reagents in seconds and enabling multiple rounds of staining of the same samples. It is non-toxic and functional in both dispersed cells and intact living tissues. We demonstrate multiparameter (n ≥ 14), non-disruptive imaging of murine peripheral blood mononuclear and bone marrow cells to profile cellular differentiation. We also show longitudinal multiplexed imaging of bone marrow progenitor cells as they develop into neutrophils over 6 days and real-time multiplexed cycling of living mouse hepatic tissues. We anticipate that SAFE will find broad utility for investigating physiologic dynamics in living systems.


Cerebral origins of the auditory projection to the superior colliculus of the cat.
The superior colliculus (SC) is critical for directing accurate head and eye movements to visual and acoustic targets. In visual cortex, areas involved in orienting of the head and eyes to a visual stimulus have direct projections to the SC. In auditory cortex of the cat, four areas have been identified to be critical for the accurate orienting of the head and body to an acoustic stimulus. These areas include primary auditory cortex (A1), the posterior auditory field (PAF), the dorsal zone of auditory cortex (DZ), and the auditory field of the anterior ectosylvian sulcus (fAES). Therefore, we hypothesized that these four regions of auditory cortex would have direct projections to the SC. To test this hypothesis, deposits of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were made into the superficial and deep layers of the SC to label, by means of retrograde transport, the auditory cortical origins of the corticotectal pathway. Bilateral examination of auditory cortex revealed that the vast majority of the labeled cells were located in the hemisphere ipsilateral to the SC injection. In ipsilateral auditory cortex, nearly all the labeled neurons were found in the infragranular layers, predominately in layer V. The largest population of labeled cells was located in the fAES. Few labeled neurons were identified in A1, PAF, or DZ. Thus, in contrast to the visual system, only one of the auditory cortical areas involved in orienting to an acoustic stimulus has a strong direct projection to the SC. Sound localization signals processed in primary (A1) and other non-primary (PAF and DZ) auditory cortices may be transmitted to the SC via a multi-synaptic corticotectal network.


Cognitive maps and the hippocampus.
Following a familiar route and finding a novel route in a familiar environment depend on different cognitive processes and representations. A recent study by Hartley et al. begins to identity the neural basis of route following and wayfinding in humans. Their study also raises important questions about the functions of the hippocampus.


Procedure for the study of acidic calcium phosphate precursor phases in enamel mineral formation.
Considerable evidence suggests that an acidic calcium phosphate, such as octacalcium phosphate (OCP) or brushite, is involved as a precursor in enamel and other hard tissue formation. Additionally, there is in vitro evidence suggesting that fluoride accelerates and magnesium inhibits the hydrolysis of OCP to hydroxyapatite (OHAp). As the amount of OCP or brushite in enamel cannot be measured directly in the presence of an excess of hydroxyapatite, a procedure was developed that allows for their indirect in vivo quantification as pyrophosphate. This permits study of the effects of fluoride and magnesium ions on enamel mineral synthesis. Rat incisor calcium phosphate was labeled by intraperitoneal injection of NaH2(32)PO4. The rats were then subjected to various fluoride and magnesium treatments with subcutaneous implanted osmotic pumps. They were then killed at predetermined intervals; the nascent sections of the incisors were collected, cleaned, and pyrolyzed at 500 degrees C for 48 hours to convert acidic calcium phosphates to calcium pyrophosphate; the pyrophosphate was separated from orthophosphate by anion-exchange chromatography; and the resulting fractions were counted by liquid scintillation spectrometry. The activities of the pyro- and orthophosphate fractions were used to calculate the amount of acidic calcium phosphate present in the nascent mineral. The results demonstrated that the percentage of radioactive pyrophosphate in nascent incisors decreased with time, with increasing serum F- concentration, and with decreasing serum magnesium content. The technique described here should prove to be a powerful new tool for studying the effects of various agents on biological mineral formation.


Characterization and bioactivity analysis of a heteropolysaccharide purified from Paenibacillus edaphicus strain UJ1.
Many polysaccharides produced by Paenibacillus spp. have attractive properties, such as rheological modification and immunomodulation. However, properties of P. edaphicus polysaccharides are not understood sufficiently. Here, the polysaccharide (PUM) was obtained from P. edaphicus strain UJ1 by batch fermentation, and the chemical characteristics, rheological and anti-inflammatory properties of PUM and its sulfate derivative (PUM-S) were investigated. The results indicated that PUM was a typical shear-thinning biopolymer with an estimated weight average molecular weight of 2.45 × 107 Da. PUM molecule consisted of D-Man, D-GlcA, D-Glc, D-Gal, and L-Fuc with the molar ratio of 3.00:1.07:3.21:0.81:0.76. It had the backbone → 3)-β-D-Man-(1 → 3)-β-D-Glc-(1 → 3)-β-D-Man-(1 → 3)β-D-Glc-(1 → 4)-β-D-GlcA-(1 → 3)-β-D-Man-(1 → and two side chains, namely, pyruvoyl-Glc-(1→ and β-L-Fuc-(1 → 3)-β-D-Gal-(1→. Moreover, PUM-S was prepared by SO3-pyridine method and had the weight average molecular weight of 1.42 × 105 Da. The bioactivity of PUM and PUM-S was analyzed in vitro in RAW 264.7 cells. The results indicated that both PUM and PUM-S facilitated cell proliferation at 50-500 μg/mL. Besides, PUM-S showed potential anti-inflammatory effect in the LPS-induced cells. According to transcription and molecular dynamics analyses, PUM-S expressed its activity probably by interacting with the Toll-like receptor 4. In general, P. edaphicus produced a polysaccharide with new chemical structure and promising rheological and bioactive properties.