Petri net-based approach to modeling and analysis of selected aspects of the molecular regulation of angiogenesis.
The functioning of both normal and pathological tissues depends on an adequate supply of oxygen through the blood vessels. A process called angiogenesis, in which new endothelial cells and smooth muscles interact with each other, forming new blood vessels either from the existing ones or from a primary vascular plexus, is particularly important and interesting, due to new therapeutic possibilities it offers. This is a multi-step and very complex process, so an accurate understanding of the underlying mechanisms is a significant task, especially in recent years, with the constantly increasing amount of new data that must be taken into account. A systems approach is necessary for these studies because it is not sufficient to analyze the properties of the building blocks separately and an analysis of the whole network of interactions is essential. This approach is based on building a mathematical model of the system, while the model is expressed in the formal language of a mathematical theory. Recently, the theory of Petri nets was shown to be especially promising for the modeling and analysis of biological phenomena. This analysis, based mainly on t-invariants, has led to a particularly important finding that a direct link (close connection) exist between transforming growth factor β1 (TGF-β1), endothelial nitric oxide synthase (eNOS), nitric oxide (NO), and hypoxia-inducible factor 1, the molecules that play a crucial roles during angiogenesis. We have shown that TGF-β1 may participate in the inhibition of angiogenesis through the upregulation of eNOS expression, which is responsible for catalyzing NO production. The results obtained in the previous studies, concerning the effects of NO on angiogenesis, have not been conclusive, and therefore, our study may contribute to a better understanding of this phenomenon.


Providing Effective Speech-Language Pathology Group Treatment in the Comprehensive Inpatient Rehabilitation Setting.
Group treatment is an integral part of speech-language pathology (SLP) practice. The majority of SLP literature concerns group treatment provided in outpatient settings. This article describes the goals, procedures, and benefits of providing quality SLP group therapy in the comprehensive inpatient rehabilitation (CIR) setting. Effective CIR groups must be designed with attention to type and severity of communication impairment, as well physical stamina of group members. Group leaders need to target individualized patient goals while creating a challenging, complex, and dynamic group context that supports participation by all group members. Direct patient-to-patient interaction is fostered as much as possible. Peer feedback supports goal acquisition by fellow group members. The rich, complex group context fosters improved insight, initiation, social connectedness, and generalization of communication skills. Group treatment provides a unique type of treatment not easily replicated with individual treatment. SLP group treatment in a CIR is an essential component of an intensive, high-quality program. Continued advocacy for group therapy provision and research into its efficacy and effectiveness are warranted.


Segmental dilatation of small bowel presenting with severe anaemia: a diagnostic puzzle.
A 7-year-old boy presented to Paediatric outpatient with worsening lethargy and tiredness. On examination he had extreme pallor. Blood investigations confirmed severe iron deficiency anaemia. He was started on iron supplements and received blood transfusion. However, the response to iron treatment was suboptimal, he therefore underwent extensive workup for the cause of iron deficiency anaemia. The barium meal showed dilated segments of ileum with two distal stenoses. The surgical resection of the involved segment was performed with end to end anastamosis. Histology of the resected segment was inconclusive of inflammatory bowel disease, malignancy or vascular malformation. The child has remained well since surgery with no further blood transfusion or iron therapy.


In vivo and in vitro deposition of immunoglobulin aggregates in the mouse eye.
The possible role of specific mechanisms involved in the adherence process of immune aggregates to tissue components of the mouse eye was investigated in an experimental animal model. Passive intravenous administration of immunoglobulin aggregates to mice, resulted in the localisation of these aggregates in various organs, including the eye. In the eye a strong localisation was seen in the episcleral capillary plexus, whereas only a weak deposition was seen in the iris, ciliary body and choroid. No deposits were seen in the retina. To investigate the role of specific receptors for immune complexes in the eye, in vitro experiments were performed, whereby immunoglobulin aggregates were layered on cryostat sections of the mouse eye. These in vitro studies also showed an adherence of immune aggregates to the episcleral capillary region, but furthermore a deposition on mast cells scattered throughout the extra-ocular muscles. The in vitro binding of immunoglobulin aggregates to the episcleral capillary plexus could be inhibited by high concentrations of Fc fragments and monomeric IgG, but not with Fab fragments or 0.5 M NaCl. The in vitro adherence of aggregates to mast cells could not be blocked by the inhibitors employed in our study and could therefore be distinguished from the interaction of aggregates with the episcleral capillary plexus. These results indicate that the ocular deposition of immunoglobulin aggregates in the episcleral capillary plexus of the mouse eye is (immune) specific and mediated by Fc receptors.


Nucleotide sequences of Escherichia coli 16-S RNA associated with ribosomal proteins S7, S9, S10, S14 and S19.
1. A ribonucleoprotein fragment containing proteins S7, S9, S10, S14, and S19 was isolated in high yield from Escherichia coli 30-S ribosomal sub-particles. The same fragment was obtained whether ribosomes from E. coli strain A19 or MRE 600 were used, despite the fact that protein S7 differs widely between the two strains. RNA was extracted from this fragment and fractionated on gels containing 7 M urea, to reveal "hidden breaks". A well-defined and reporducible pattern of RNA fragments was obtained, with the main components being approximately 300, 240, 130, 115 and 75 nucleotides in length, respectively. The pattern of RNA fragments obtained was also independent of the strain of E. coli used. 2. Two-dimensional fingerprints were made from ribonuclease T1 hydrolysates of these RNA fragments, labelled with 32P, and the oligonucleotides were further analysed by digestion with either ribonuclease A or U2. The data obtained were fitted in detail to the new 16-S RNA sequence map of Ehresmann et al. (1975). Again no significant differences were observed between the RNA from E. coli A19 or MRE 600. The RNA sequences found lay in the region O'-D-E'-K-P-P'-E-A of the 16-S RNA, with a clear excision of several nucleotides in section E'-K. The total sequence length covered was approximately 430 nucleotides.


Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB.
Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.


A COX-2 Inhibitor Does Not Interfere With the Bone-Protective Effects of Loading in Male Mice With Arthritis.
Mechanical loading enhances bone strength and counteracts arthritis-induced inflammation-mediated bone loss in female mice. It is unknown whether nonsteroidal anti-inflammatory drugs (NSAIDs; eg, COX-2 inhibitors) can reduce inflammation without affecting the loading-associated bone formation in male mice. The aim of this study was to investigate if loading combined with a COX-2 inhibitor (NS-398) could prevent arthritis-induced bone loss and inflammation in male mice. Four-month-old male C57BL/6J mice were subjected to axial tibial mechanical loading three times/week for 2 weeks. Local mono-arthritis was induced with a systemic injection of methylated bovine serum albumin on the first day of loading, followed by a local injection in one knee 1 week later. The arthritis induction, knee swelling, bone architecture, and osteoclast number were evaluated in the hind limbs. C-terminal cross-links as a marker for osteoclast activity was measured in serum. Compared with loading and arthritis alone, loading of the arthritic joint enhanced swelling that was partly counteracted by NS-398. Loading of the arthritic joint enhanced synovitis and articular cartilage damage compared with loading alone. Loading increased cortical bone and counteracted the arthritis-induced decrease in epiphyseal bone. NS-398 did not alter the bone-protective effects of loading. C-terminal cross-links, a bone resorption marker, was increased by arthritis but not loading. In conclusion, loading prevented arthritis-induced epiphyseal and metaphyseal bone loss, and NS-398 reduced knee swelling without affecting the bone-protective effects of loading. If our results can be extrapolated to the human situation, specific COX-2 inhibitors could be used in combination with loading exercise to prevent pain and swelling of the joint without influencing the bone-protective effects of loading. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Microgravity reduces the differentiation of human osteoblastic MG-63 cells.
Spaceflight leads to osteopenia in both humans and animals, principally as a result of decreased bone formation, which might be the consequence of impaired osteoblast differentiation. The effect of microgravity on osteoblast differentiation in vitro was investigated using the human osteosarcoma cell line MG-63. Genes related to matrix formation and maturation were quantified both at the protein and mRNA level in untreated and hormone-treated (dihydroxyvitamin D3 [1,25(OH)2D3], 10(-7) M; transforming growth factor beta2 (TGF-beta2), 10 ng/ml) cells cultured for 9 days under microgravity conditions aboard the Foton 10 satellite and compared with ground and inflight unit-gravity cultures. The expression of alkaline phosphatase (ALP) activity following treatment at microgravity increased only by a factor of 1.8 compared with the 3.8-fold increase at unit-gravity (p < 0.01), whereas no alteration was detected in the production of collagen type I between unit- and microgravity. In addition, gene expression for collagen Ialpha1, ALP, and osteocalcin following treatment at microgravity was reduced to 51, 62, and 19%, respectively, of unit-gravity levels (p < 0.02). The lack of correlation between collagen type I gene and protein expression induced by microgravity is most likely related to the different kinetics of gene and protein expression observed at unit-gravity: following treatment with 1,25(OH)2D3 and TGF-beta2, collagen Ialpha1 mRNA increased gradually during 72 h, but collagen type I production was already maximal after treatment for 48 h. In conclusion, microgravity decreases the activity of osteoblasts in vitro; in particular the differentiation of osteoblasts in response to systemic hormones and growth factors is reduced by microgravity.


HPLC determination of the composition and stability of blackcurrant anthocyanins.
High-performance liquid chromatography with UV and mass spectrometry detectors are used to monitor the composition and stability of anthocyanins in blackcurrants harvested from different Ribes nigrum breeds at various ripeness phases. The highest amounts of pigments are found in overripe berries. The concentration of anthocyanins is higher in the berries of late blackcurrant breeds (Vakariai and Ben Alder). Delphinidin- 3-rutinoside is the dominant component in the reddish color berries (onset of ripening), and cyanidin-3-rutinoside is a major pigment in the black ones (ripe berries). Studies of the effect of temperature and light on the stability of the main pigments in blackcurrants show that aqueous solution prepared from a dry colorant is more stable when compared with the liquid water and ethanol extracts of coloring substances. Cyanidin-3-rutinoside is found to be the most thermally stable anthocyanin.


Evaluation of shoulder girdle strength more than 12 month after modified radical mastectomy and axillary nodes dissection.
Muscle strength is necessary for upper body normal function. Upper extremity function impairments have been reported in breast cancer (BC) survivors. It is not possible to know precisely if cancer adjuvant therapy such as radiation and chemotherapy had any effect on the unaffected arm. The aim of this study was to compare shoulder girdle strength among women with BC and similarly aged women without cancer. Thirty-three postmenopausal women (51 ± 6.46 years) with BC who underwent surgery, chemotherapy, and radiation therapy and 30 healthy postmenopausal women (53.26 ± 5.05 years) were selected. Muscle strength was measured using a handheld dynamometer for flexion, horizontal adduction, internal and external rotation, scapular abduction and upward rotation, scapular depression, and adduction. Data were analyzed by multivariate analysis of variance (P < 0.05). The findings indicated significant differences between groups of 6 of the shoulder girdle strength measure (flexion (P = 0.003), internal rotation (P = 0.001), external rotation (P = 0.040), scapular abduction and upward rotation (P = 0.001), scapular depression and adduction (P = 0.025), and shoulder horizontal adduction (P = 0.00)). Patients showed significantly lower strength compared with healthy controls (flexion = 34.3%, abd = 64.2%, int.rot = 51.2%, ext.rot = 32.4%, hor.add = 58.06, and depression = 35.2%). The results indicate that the shoulder girdle strength in women with BC decreased compared with healthy women without BC. Therefore, during the treatment of patients with BC, designing of training programs and rehabilitation programs need to be performed on shoulder girdle strength factors in patients undergoing mastectomy with axillary surgery and radiation therapy.


Sucrose Improves Insecticide Activity Against Drosophila suzukii (Diptera: Drosophilidae).
The addition of sucrose to insecticides targeting spotted wing drosophila, Drosophila suzukii (Matsumura), enhanced lethality in laboratory, semifield, and field tests. In the laboratory, 0.1% sucrose added to a spray solution enhanced spotted wing drosophila feeding. Flies died 120 min earlier when exposed to spinosad residues at label rates enhanced with sucrose. Added sucrose reduced the LC50 for dried acetamiprid residues from 82 to 41 ppm in the spray solution. Laboratory bioassays of spotted wing drosophila mortality followed exposure to grape and blueberry foliage and/or fruit sprayed and aged in the field. On grape foliage, the addition of 2.4 g/liter of sugar with insecticide sprays resulted in an 11 and 6% increase of spotted wing drosophila mortality at 1 and 2 d exposures to residues, respectively, averaged over seven insecticides with three concentrations. In a separate experiment, spinetoram and cyantraniliprole reduced by 95-100% the larval infestation of blueberries, relative to the untreated control, 7 d after application at labeled rates when applied with 1.2 g/liter sucrose in a spray mixture, irrespective of rainfall; without sucrose infestation was reduced by 46-91%. Adding sugar to the organically acceptable spinosyn, Entrust, reduced larval infestation of strawberries by >50% relative to without sugar for five of the six sample dates during a season-long field trial. In a small-plot field test with blueberries, weekly applications in alternating sprays of sucrose plus reduced-risk insecticides, spinetoram or acetamiprid, reduced larval infestation relative to the untreated control by 76%; alternating bifenthrin and phosmet (without sucrose) reduced infestation by 65%.


A Sensitive Liquid Chromatography-Mass Spectrometry Method for Determination of 14-Deoxy-12(R)-Sulfo Andrographolide Concentration in Rat Plasma and its Application to a Pharmacokinetic Study.
Andrographolide is a promising natural substance with numerous pharmacotherapy uses. 14-deoxy-12(R)-sulfo andrographolide (SAP) is the main metabolite of andrographolide in the intestine. To investigate the pharmacokinetic properties of SAP, a precise and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of SAP concentration in rat plasma was developed and validated in this study. Chromatographic separation was achieved on an Acpuity UPLC BEH C18 column with gradient elution that consisted of methanol and water at a flow rate of 0.3 mL/min. MS/MS detection was carried out by the multiple reaction monitoring (MRM) mode with negative electrospray ionization (ESI-) source, with the transitions of m/z 413.2→m/z 287.2 for SAP and m/z 269→m/z 133 for genistein [which was used as an internal standard (IS)]. The calibration curve of SAP was linear over the concentration range of 5-120 ng/mL. The selectivity, precision, accuracy, extraction recovery, matrix effect, and stability of the method were within acceptable ranges. This SAP quantification method was then successfully applied to a pharmacokinetic study of SAP. The area under the curve (AUC) of SAP in rats treated with SAP at 60 mg/kg by intravenous administration was 7498.53 ± 2405.02 mg/L·min. The AUC of SAP in rats treated with SAP at 60 mg/kg by oral administration was 97.74 ± 39.56 mg/L·min. Thus, the absolute oral bioavailability of SAP was determined to be 1.40%.


[Pituitary adenoma calcification].
Three hundred and eighteen cases of functioning and non-functioning pituitary adenoma were examined by histological, immunocytochemical and electronmicroscopic technique. Fourty-four of them (13.8%) showed evidence of calcospherites in the tumor tissues. A high incidence of calcospherite is found in functioning adenoma, but not in non-functioning adenoma. Calcification was seen most frequently in cases of prolactinoma (23), GH secreting (7), or GH + PRL tumor (2) and less in adrenocorticotropic hormone secreting adenoma (2) and follicle stimulating hormone secreting adenoma (1). Prolactin and growth hormone might be involved in the control of calcium metabolism. This is because, following adenomectomy in patients with prolactinoma or GH-secreting adenoma with hypercalcemia, there is normalization of serum PRL and GH with reduction in serum calcium. Calcospherite is produced in all of metastatic calcification, arterial calcification, dystrophic calcification and calcinosis. In cases of non-functioning adenoma however, the mechanism is believed to by dystrophic calcification.


Potential of powdered activated mustard cake for decolorising raw sugar.
Carbon decolorisation has become customary in the food processing industries; however, it is not economical. Extensive research has therefore been directed towards investigating potential substitutes for commercial activated carbons which might have the advantage of offering an effective, lower-cost replacement for existing bone char or coal-based granular activated carbon (GAC). The physical (bulk density and hardness), chemical (pH and mineral content) and adsorption characteristics (iodine test, molasses test and raw sugar decolorisation efficiency) of powdered activated mustard cake (PAMC) made from de-oiled mustard cake were determined and compared to commercial adsorbents. Although the colour removal efficiency of the PAMC is lower than that of commercial materials, it is cost effective and eco-friendly compared to the existing decolorisation/refining processes. To reduce the load on GAC/activated carbon/charcoal, PAMC could be used on an industrial scale. A decolorisation mechanism has been postulated on the basis of oxygen surface functionalities and surface charge of the PAMC and, accordingly, charge transfer interaction seems to be responsible for the decolorisation mechanism. In addition, a complex interplay of electrostatics and dispersive interaction seem to be involved during the decolorisation process. A low-cost agricultural waste product in the form of de-oiled mustard cake was converted to an efficient adsorbent, PAMC, for use in decolorising raw as well as coloured sugar solutions. The physical, chemical, adsorption characteristics and raw sugar decolorisation efficiency of PAMC were determined and compared to those of commercial adsorbents. The colour removal efficiency of the PAMC is lower than that of commercial materials but it is cost effective and eco-friendly as compared to existing decolorisation/refining processes. The availability of the raw material for the production of PAMC further demands its use on an industrial scale.


[When and how to withdraw glucocorticoid therapy in elderly?].
Glucocorticoid therapy (GCT) is commonly used for the treatment of many chronic diseases. It is prescribed in almost 3% of the population > or = 70-years-old. Numerous short- and long-term side effects can occur even at low doses. GCT should be preceded by screening for and stabilization of disorders that can be aggravated by treatment. During GCT regular monitoring for side effects, adjusting of the treatment to the lowest effective dose and regular re-evaluation of the indication are required. The GC withdrawal protocols are not evidence-based and are chosen essentially according to the risk of reactivation of the treated disorder. The risk of secondary adrenal insufficiency is real but quite low, and does not in itself justify the continuation of a GCT.


Sedentary versus active leisure activities and their relationship with sleeping habits and body mass index in children of 9 and 10 years of age.
A random sample of 291 9- and 10-year-old schoolchildren from Asturias (Spain) was taken. Using path analysis, a model was tested in which bedtime, the number of hours spent sleeping and leisure activities were the independent variables and the body mass index was the dependent variable. The results show that sedentary and active leisure time and hours spent sleeping are predictors of the body mass index in children. Those children who go to bed late and who use that extra time to watch the television or play with the computer tend to have a greater body mass index, while those children who go to bed earlier and have spent more time reading or playing in the park or at home have a lower body mass index. Encouraging active leisure activities can have an extremely positive effect on their body mass index.


Sudden infant death and infanticide.
The hypothesis, advanced by Asch (Mt Sinai J Med NY 35:214-220, 1968), that a majority of sudden infant death syndrome (SIDS) cases are actually infanticides, is addressed by examination of age comparable infant homicide rates (United States, 1950-1974) and consideration of current theory regarding SIDS pathogenesis. The analysis provides no support for the hypothesis.


Abundance and function of bacteria in the Southern Ocean.
The very low water temperatures existing in polar oceans that experience seasonal advance and retreat of pack ice do not inhibit the presence of large bacterial populations. Bacteria may contribute significantly to the energy transfers within the Southern Ocean. In the last decades, notable progress has been made in the knowledge of the role of marine bacteria in the Southern Ocean. A short overview of the abundance and function ofAntarctic marine bacteria is given, with respect to metabolic activity. The importance of spatial and temporal variability is described. The ecological function of Antarctic marine bacterioplankton is discussed. Depending on food web structure, bacteria may be either a link in food webs supporting metazoan production, or a sink where bacterial production is metabolised by microorganisms. In the more oligotrophic areas and during certain periods of the year bacterial biomass dominates phytoplankton. The microbial food web is therefore the dominant pathway for carbon and energy flow in Antarctic seawater.


Dependence of the virial exciton model on basis set and exact-exchange fraction.
The exchange-only (uncorrelated) singlet-triplet energy difference in one-electron excited configurations is 2Kif, where Kif is the Coulomb self-energy of the product of the transition orbitals. A nonempirical, virial-theorem argument was presented by Becke [J. Chem. Phys. 148, 044112 (2018)] that the correlated singlet-triplet energy difference should be half of this, namely, Kif. This incredibly simple result gave HOMO-LUMO singlet excitation energies in small-molecule benchmark sets as good as the popular TD-B3LYP time-dependent approach to excited states. In a subsequent application to long-chain polyenes approaching the polyacetylene limit [A. D. Becke, J. Chem. Phys. 149, 081102 (2018)], we found a dramatic dependence of the optical gap on the amount of exact exchange in the density functionals used to generate the orbitals. Here, we assess the effect of the exact-exchange fraction in standard small-molecule tests. Also, we assess two basis-set extremes: the highly practical cc-pVDZ basis set and the higher-quality aug-cc-pVTZ.


Inhibitory sharpening of receptive fields contributes to whisker map plasticity in rat somatosensory cortex.
The role of inhibition in sensory cortical map plasticity is not well understood. Here we tested whether inhibition contributes to expression of receptive field plasticity in developing rat somatosensory (S1) cortex. In normal rats, microiontophoresis of gabazine (SR 95531), a competitive gamma-aminobutyric acid (GABA)-A receptor antagonist, preferentially disinhibited surround whisker responses relative to principal whisker responses, indicating that GABA(A) inhibition normally acts to sharpen whisker tuning. Plasticity was induced by transiently depriving adolescent rats of all but one whisker; this causes layer 2/3 (L2/3) receptive fields to shift away from the deprived principal whisker and toward the spared surround whisker. In units with shifted receptive fields, gabazine preferentially disinhibited responses to the deprived principal whisker, unlike in controls, suggesting that GABA(A) inhibition was acting to preferentially suppress these responses relative to spared whisker responses. This effect was not observed for L2/3 units that did not express receptive field plasticity or in layer 4, where receptive field plasticity did not occur. Thus GABA(A) inhibition promoted expression of sensory map plasticity by helping to sharpen receptive fields around the spared input.


High-resolution imaging at the cellular and subcellular levels in flattened whole mounts of early zebrafish embryos.
We describe a rapid and sensitive method for high-resolution imaging at the cellular and subcellular levels in the whole-mount zebrafish embryo. The procedure involves fixing and staining the embryo, followed by deyolking and flattening it under a cover slip, to produce a planar mount that is 20 to 100 microns thick. Such a flattened whole mount allows imaging with a spatial resolution of approximately 500 nm in the x-y plane and does not require the use of embedding, sectioning, confocal microscopy, or computational deblurring procedures. We can resolve all individual nuclei and chromosome sets in the embryo, up to the late gastrula stage (10,000 cell stage). In addition, older embryos (through the segmentation stage) can also be examined, with the preservation of significant morphological detail. Because of its ability to resolve subcellular detail, the flattened whole-mount method can provide significant biological information beyond what can be obtained from conventional (three-dimensional) whole mounts. We have used the flattened whole-mount method to study subcellular events related to progression through the cell cycle or to apoptosis, in cells of the early zebrafish embryo. A specific DNA-binding dye (Hoechst 33258) or an antibody against a chromosomal protein (histone H1) was used to stain the nuclei of individual cells in the embryo. This allowed us to determine the spatial positions of all the individual cells, and also their stages in the cell cycle. A terminal transferase (TUNEL) assay was used to detect apoptotic cells. This combination of specific stains allowed us to study the behaviors of groups of cells in situ, within the developing zebrafish embryo.


Targeting the PI3K/Akt/mTOR pathway in castration-resistant prostate cancer.
The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a key signaling pathway that has been linked to both tumorigenesis and resistance to therapy in prostate cancer and other solid tumors. Given the significance of the PI3K/Akt/mTOR pathway in integrating cell survival signals and the high prevalence of activating PI3K/Akt/mTOR pathway alterations in prostate cancer, inhibitors of this pathway have great potential for clinical benefit. Here, we review the role of the PI3K/Akt/mTOR pathway in prostate cancer and discuss the potential use of pathway inhibitors as single agents or in combination in the evolving treatment landscape of castration-resistant prostate cancer.


Comparative genome-wide survey of single nucleotide variation uncovers the genetic diversity and potential biomedical applications among six Macaca species.
Macaca is of great importance in evolutionary and biomedical research. Aiming at elucidating genetic diversity patterns and potential biomedical applications of macaques, we characterized single nucleotide variations (SNVs) of six Macaca species based on the reference genome of Macaca mulatta. Using eight whole-genome sequences, representing the most comprehensive genomic SNV study in Macaca to date, we focused on discovery and comparison of nonsynonymous SNVs (nsSNVs) with bioinformatic tools. We observed that SNV distribution patterns were generally congruent among the eight individuals. Outlier tests of nsSNV distribution patterns detected 319 bins with significantly distinct genetic divergence among macaques, including differences in genes associated with taste transduction, homologous recombination, and fat and protein digestion. Genes with specific nsSNVs in various macaques were differentially enriched for metabolism pathways, such as glycolysis, protein digestion and absorption. On average, 24.95% and 11.67% specific nsSNVs were putatively deleterious according to PolyPhen2 and SIFT4G, respectively, among which the shared deleterious SNVs were located in 564⁻1981 genes. These genes displayed enrichment signals in the 'obesity-related traits' disease category for all surveyed macaques, confirming that they were suitable models for obesity related studies. Additional enriched disease categories were observed in some macaques, exhibiting promising potential for biomedical application. Positively selected genes identified by PAML in most tested Macaca species played roles in immune and nervous system, growth and development, and fat metabolism. We propose that metabolism and body size play important roles in the evolutionary adaptation of macaques.


Factors Associated with Survival in Anaplastic Thyroid Carcinoma: A Multicenter Study from the ENDOCAN-TUTHYREF Network.
Background: Anaplastic thyroid carcinoma (ATC) is a rare and frequently fatal type of thyroid cancer. The degree of heterogeneity in survival rates for ATC is incompletely studied. This study evaluated the factors associated with overall survival (OS) of patients with ATC using multicenter real-world data from a national tertiary care center network in France. Methods: In this multicenter, retrospective cohort study, all patients with ATC diagnosed between 2010 and 2020 were identified from the national database of the French ENDOCAN-TUTHYREF network. Factors associated with OS were examined in multivariable analyses using Cox proportional hazards models. Results: The study included 360 patients. Of these, 220 (61%) were female and the median age was 72 years (interquartile range: 62-80). The percentages of patients with pure and mixed (synchronously-transformed) ATC (p-ATC and st-ATC) were 62.5% and 26.7%, respectively. The median OS was 6.8 months [confidence interval, CI: 5.5-8.1]: not reached for stage IVa, 11.4 months [8.2-17.8] for IVb, and 4.6 months [3.5-5.7] for IVc. Surgery, radiation therapy to the neck, chemotherapy, and best supportive care were administered to 69 (19.2%), 214 (59.4%), 254 (70.6%), and 66 (18.3%) patients, respectively. In a multivariable analysis, including stage IVb-IVc patients, significantly higher OS was observed in patients with Eastern Cooperative Oncology Group performance-status of 0-1 (hazard ratio [HR], 0.6; [CI, 0.4-0.9], p < 0.02), stage IVb [HR, 0.5; CI, 0.4-0.8, p < 0.001], and multimodal treatment (surgery and chemoradiotherapy) [HR, 0.07; CI, 0.04-0.1, p < 0.001]. Variables associated with significantly worse OS included: p-ATC (vs. st-ATC) [HR, 1.83; CI, 1.33-2.51, p = 0.001] and a neutrophil-to-lymphocyte ratio (NLR) >5.05 [HR, 2.05, CI, 1.39-3.05, p < 0.001]. Conclusions: Factors independently associated with improved OS in ATC included: European Cooperative Oncology Group performance status, disease stage, multimodality treatment, synchronously transformed ATC, and lower NLR. Long-term OS was observed in selected patients with ATC who underwent multimodal treatment.


Sign changes of intrinsic spin Hall effect in semiconductors and simple metals: first-principles calculations.
First-principles calculations are applied to study spin Hall effect in semiconductors and simple metals. We found that intrinsic spin Hall conductivity (ISHC) in realistic materials shows rich sign changes, which may be used to distinguish the effect from the extrinsic one. The calculated ISHC in n-doped GaAs can be well compared with experiment, and it differs from the sign obtained from the extrinsic effect. On the other hand, the ISHC in W and Au, which shows opposite sign, respectively, is robust and not sensitive to the disorder.


The epidemiology of pancreatic diseases in Japan.
We reviewed the trends and death rates of pancreatic cancer and pancreatitis in Japan over the past four decades. It is a disturbing fact that the death rate due to pancreatic cancer is rising, parallel to that of lung cancer and colon cancer and that it is affecting primarily the elderly 65 years and older in both sexes. The cause of this increase is partially attributable to improvements in the diagnosis, changes in life-style, and smoking. The death rate due to chronic and acute pancreatitis has remained constant during the past four decades.


Design and synthesis of AX7574: a microcystin-derived, fluorescent probe for serine/threonine phosphatases.
The design and synthesis of AX7574, a microcystin-derived probe for serine/threonine phosphatases, is described. A key step in the synthesis was the conjugation under basic conditions of a tetramethylrhodamine 1,3-diketone derivative to the arginine side chain present in microcystin-LR. The resulting conjugate specifically labeled the active site of protein phosphatases 1 (PP-1) with a 1:1 stoichiometry and IC50 of 4.0 nM. AX7574 was used to isolate and identify PP-1, PP-2A, PP-4, and PP-6 in Jurkat cells. Finally, AX7574 was able to record changes in the phosphatase activity levels of calyculin A treated Jurkat cells versus untreated control cells.


Close to me: enhancing kangaroo care practice for NICU staff and parents.
The benefits of kangaroo care (KC) are well supported by previously published studies, yet KC is offered inconsistently and faces obstacles in the neonatal intensive care unit (NICU). The March of Dimes designed Close to Me to facilitate and increase KC in NICUs. The program incorporates KC education for nurses and parents, as well as awareness and comfort components. The purpose of this study was to assess whether Close to Me increased favorable attitudes toward KC among nurses and parents, and changed nurse and parent behaviors to implement KC earlier, more often and for longer duration. This study took place in 5 NICUs with 48 nurse participants and 101 parent participants. It used a pre-/postprogram implementation design for nurses and a nonequivalent comparison versus intervention group design for parents. Nurses and parents were surveyed on knowledge, attitudes, perceived behavioral control, and behavior. Comparisons were made pre- and postprogram implementation for nurses and between intervention and comparison groups for parents. Nurse focus groups were conducted pre- and postimplementation and analyzed using a constant comparative analysis method. Parents recorded care behaviors and satisfaction in journals, which were analyzed similarly. After the Close to Me intervention, nurses reported more positive attitudes toward KC (P = .04), increased transfer of ventilated babies from incubators to parents (P = .01), and more parents requesting KC. Parents who received Close to Me had greater knowledge about KC (P = .03) compared with those who did not. With the Close to Me intervention, all babies born at less than 28 weeks' gestation had KC by the age of 12 days, whereas without the intervention, some did not have KC until the age of 31 days (P < .05). March of Dimes Close to Me improved knowledge and behavior regarding KC in NICUs. By offering KC education to parents, providing KC awareness and comfort components, and providing information and encouragement on the benefits and feasibility of KC to nurses, hospitals can potentially promote earlier and more frequent use of KC, particularly with infants born less than 28 weeks' gestation.


Effect of infant formula with probiotics on intestinal microbiota.
Weaning during infancy refers to the initiation of complementary food to breast milk. During weaning, there are significant changes on the gastrointestinal microbiota. Deleterious alterations of the gastrointestinal microbiota can result in pathological processes while measures that stimulate its development and stability, like the use of probiotics, are beneficial. The mechanisms by which probiotics achieve their effects have not been clearly established. Present work compares the microbial composition of feces from infants that were weaned to regular family food, formula with probiotics (B. Lactis BL y S. Thermophilus) or formula without probiotics. Accordingly, analysis of rDNA of microbial fecal samples by molecular techniques was used. Formula with or without probiotics was well tolerated and safe for all participating children. Probiotics present in formula were viable and susceptible to culture. There was not difference on physical growth or development among all participants. The microbiota of children supplemented with formula with- or without probiotics was different than that observed in children supplemented with regular food. It was not possible to determine enrichment of B. Lactis BL and S. Thermophilus in the feces of children that consumed the probiotics. Present work contributes to the understanding of probiotics effects in human health.


Research on the differentiation of human and murine neuroblastoma cells.
In vitro, we were able to induce a differentiation of human (SK-N-MC, IMR-32, Leo-2) and murine neuroblastoma cells (NA-2, C-1300, NIE-115) with dibutyryl cyclic 3'5'-adenosine monophosphate (dbcAMP), hypothalamic factor (HF), and somatostatin. As morphological criteria of cellular differentiation we used the decrease in cell proliferation and the formation of neurites. Functional parameters were the increase of A cholinesterase activity, cAMP level, and protein content, and the decrease of cGMP level. After application of dbcAMP and HF, the effects were stronger than after somatostatin. We believe that the action of HF and somatostatin is caused by an increase in cAMP levels. In the in vivo experiments, human and murine neuroblastoma cells (NA-2, C-1300, and Leo-2) were transplanted into nude/nude mice. After HF treatment of 14 mice with NA-2 tumors, 4 of the mice were tumor-free, and mean tumor weight was reduced to one-third of the controls. Of the animals with C-1300 and Leo-2 tumors, half became tumor-free, and mean tumor weight was reduced to one-fourth. The results indicate that the induction of cellular differentiation by factors and hormones may in future become a method of therapy for human neuroblastoma.


Long-term results of treatment of Cushing's disease by adrenalectomy.
Patients treated by adrenalectomy for suspected Cushing's syndrome were reviewed for the incidence to early and late complications, side effects, survival, and quality of life. Of a total of 141 patients, 109 had Cushing's disease, and were treated with subtotal (n = 15) or total (n = 94) adrenalectomy. All hospital charts were reviewed, and surviving patients were asked to fill in a questionnaire. Ten patients died in hospital. Morbidity was 13% (n = 18). Five patients required reoperation because of recurrent adrenal hyperplasia after subtotal adrenalectomy (n = 3) or incomplete adrenalectomy (n = 2). All patients received conventional corticosteroid supplementation. Ten patients developed Nelson's syndrome 3-20 years after adrenalectomy. Of the 109 patients with Cushing's disease 80 were alive 1-34 years after operation. Only four late deaths were related to Cushing's disease: 3 postoperative deaths followed reoperation and 1 was the result of an Addisonian crisis. About two thirds of the patients interviewed had satisfactory quality of life and were able to work. Total bilateral adrenalectomy has a five to seven fold higher perioperative mortality than transphenoidal operations. The prognosis of patients who survive the early postoperative period, however, is comparable to that of the general population.


Intrathoracic lymphadenopathy in postprimary tuberculosis.
In the past, hilar or mediastinal lymphadenopathy was considered by many to be a feature of only the primary or first infection with Mycobacterium tuberculosis, and to exclude the diagnosis of reactivation or postprimary tuberculosis. In a series of 56 adult patients with documented postprimary disease due to M tuberculosis, we found hilar or mediastinal lymphadenopathy in three cases (5%). Although intrathoracic lymphadenopathy was more common in primary tuberculosis, we do not believe that intrathoracic lymphadenopathy is as specific for primary tuberculosis, particularly in the adult, as was once thought. For this reason, we believe that the roentgenographic demonstration of intrathoracic lymphadenopathy should not be used as a definitive research or clinical criterion for primary tuberculosis in an adult.


Endovascular bypass for salvage of vascular access in hemodialysis catheter-consigned patients.
This study was performed to retrospectively assess the efficacy of percutaneous creation of an intervascular bypass with or without stent graft deployment (endovascular bypass) for salvage of abandoned vascular access sites in hemodialysis catheter-consigned patients. Salvage of abandoned vascular access sites was attempted in 16 patients with hemodialysis catheters. These vascular access sites were salvaged using endovascular bypass techniques to redirect the access flow to a nonarterialized vein as a new outflow conduit or cannulation segment. The postintervention primary, assisted primary, and secondary patency rates of the access site and bypass were calculated using the Kaplan-Meier method. The procedural and clinical success rates were both 100%. The postintervention primary patency rate of the bypass and access site at 360 days was 75.7 ± 12.5% and 56.8 ± 14.9%, respectively. The mean follow-up period was 461.9 days (range: 121-900 days). No major complications were observed. One bare bypass tunnel rupture and one pseudoaneurysm were noted during the procedure. Salvage of abandoned vascular access sites for hemodialysis catheter-consigned patients can be technically feasible and clinically successful using endovascular bypass techniques in selected patients when surgical revision is not considered or is not possible.


Screening of pesticide distributions in foods of animal origin: a matrix-based approach for biotransfer factor modeling of grazing mammals.
Pesticides are detected in a wide array of foods of animal origin, posing a threat to food safety and human health. Here, to facilitate the management of pesticide residues in livestock products, we proposed a screening model for simulating pesticide biotransfer factors (BTFs, ratio of steady-state pesticide concentration between animal tissues and feed) in mammalian bodies. The proposed model was developed based on simple matrix algebra using first-order kinetics. Simulation of over 700 pesticides in common food products derived from cattle and sheep indicated that pesticide biotransfer is a balancing process between uptake efficiency from the gut lumen and the uptake-elimination ratio (ratio of the overall uptake and elimination rate constants) in individual tissues. Furthermore, we parameterized the developed BTF model using the octanol-water partition coefficient. The simulated pesticide BTFs could be categorized into three lipophilicity phases, namely, the lipophilicity-boosting (log KOW < 4), lipophilicity-balancing (4 ≤ log KOW ≤ 8), and lipophilicity-limiting (log KOW > 8) phases, and the simulated general trends of BTFs were consistent with the experimental data. Although the metabolic rate constants of pesticides in mammalian bodies warrant further evaluation, the model proposed here can assist in the risk assessment and regulatory management of pesticide residues in foods of animal origin.


[Cranio-mandibular eosinophilic granuloma starting in the lung].
The authors describe the case of a young man with a worsening general condition who was found to be suffering from bilateral pulmonary infiltration. Pulmonary tuberculosis was diagnosed after clinical and radiological investigation and specific antituberculous treatment was instituted. When the patient later complained of headaches, he was found to have cranial and mandibular lacunae which were treated surgically. Pathological examination showed this to be a case of eosinophilic granuloma.


An Evaluation of the Communication at End-of-Life Education Program for Personal Support Workers in Long-Term Care.
Background: Communication skills are crucial for personal support workers (PSWs) to foster therapeutic relationships with the residents and their families in the long-term care (LTC) setting. Aim: To evaluate the impact of the Communication at End-of-Life (CEoL) Education Program on the competency and confidence of PSWs working in LTC to communicate about palliative and end-of-life care, and factors affecting their involvement in palliative and end-of-life care. Setting/Participants: PSWs from 35 LTC homes in Ontario, Canada, who participated in the CEoL Education Program between January and March 2019. Design: Mixed-methods evaluation using pre- (n = 178) and post-workshop (n = 113) surveys capturing the attitudes and beliefs toward death and dying; relationships with residents and families; and PSWs' participation in end-of-life care. Follow-up interviews were conducted between February and March 2019 with 21 PSWs to examine facilitators and barriers that affected their confidence in engaging in palliative care. Results: We observed significant improvements in all three domains, with the greatest increase (11%, p < 0.001) in the proportion of participants who responded "Often" or "Always" in the participation in end-of-life care domain. Specifically, we observed PSWs' elevated confidence in speaking with families of the residents about end-of-life, discussing goals and plans with the residents, and realizing that a "good death" is possible. Time constraints and staff shortages were recurrent themes that hindered many participants' ability to provide resident-centered care. Conclusions: This evaluation demonstrates that CEoL Education Program was associated with improved PSW competency and confidence in supporting palliative and end-of-life care in LTC settings.


[Identification and the Related Molecular Mechanism of B(A)04 Allele].
To investigate the identification and molecular biological mechanism of a case of B(A)04 allele. The ABO blood groups of the proband and his nine family members were analyzed serologically and DNA sequencing was used to accurately determine the genotypes of these ten specimens. The cartoon models of local active center of enzymes of the GTA,GTB and the GTB mutant were constructed to explore the possible molecular mechanism leading to abnormal enzyme-catalyzed A antigen synthesis. The serological results suggested that the ABO blood groups of the proband, his elder brother and his maternal grandmother were AweakB or B(A); the ABO blood group of his mother was type AB, his uncle and elder aunt were type B, and his father was type O. ABO blood group gene sequencing results showed that 6 out of 10 members of the family carried the B(A)04 allele. Molecular structure models suggested that the spatial distance of critical amino acid residues in the catalytic center of the GTB mutant enzyme was greater than that of GTB, which might cause the enzyme to abnormally catalyze the synthesis of A antigen. The characteristics of serological reactions of B(A) blood subgroup are complicated, and its identification needs to be combined with molecular biology and pedigree investigation. It is speculated that the B(A) phenotype may be associated with a larger volume of the catalytic center in the GTB mutant.


Poor agreement between data from the National Patient Registry and the Danish Patient Insurance Association.
Septic arthritis after knee arthroscopy requires in-patient treatment and should thus be reported to the National Patient Registry (NPR). It also meets the requirements for financial compensation if claimed to the Danish Patient Insurance Association (DPIA). The aim of this study was to assess data from the two independent data sources, the NPR and DPIA, with a view to comparing the registration of septic arthritis after knee arthroscopy. This was a retrospective study assessing two three-year periods. From the NPR, we initially received all contacts coded as arthroscopic knee surgery. A second NPR query was made for patients found in the first query who had had a hospital contact within 30 days postoperatively with codes indicating septic arthritis (450 patients). Correspondingly, the DPIA files of patients claiming an infection following knee arthroscopy were searched to identify those (157 patients) with post-arthroscopic septic arthritis. We found poor agreement between the 450 patients in the second NPR data extraction and the 157 verified patients from the DPIA. Only 105 patients from DPIA were found in the NPR, while 52 patients in the DPIA were not returned as part of the second NPR data extraction. Coding of infections after arthroscopy in the NPR is inconsistent and incomplete. An underreporting of septic arthritis to the DPIA might exist.


Ovarian Function Recovery During Anastrozole in Breast Cancer Patients With Chemotherapy-Induced Ovarian Function Failure.
Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen. We identified all patients with chemotherapy-induced ovarian function failure. Women who underwent a bilateral ovariectomy or used luteinizing hormone-releasing hormone agonists before random assignment were excluded. Plasma estradiol and follicle-stimulating hormone levels were monitored until 30 months after random assignment at local laboratories. We aimed to determine the ovarian function recovery (OFR) rate during AI use by the cumulative incidence competing risk method and analyzed the trend of estradiol levels during AI use by a nested case-control approach in which a subset of control subjects were compared with the OFR patients excluding the value at OFR diagnosis. The 329 eligible patients had a median age of 50.0 years (range = 45-57 years) at random assignment. Thirty-nine patients developed OFR, corresponding with a 30-month recovery rate of 12.4%. Of these, 11 (28.2%) were age 50 years or older at AI initiation. The estradiol level decreased statistically significantly by 37.8% (95% CI = 27.4% to 46.7%) over the initial 30 months of AI treatment in both groups. However, the estradiol levels in the women who experienced OFR remained statistically significantly higher (difference = 20.6%, 95% CI = 2.0% to 42.7%) prior to OFR diagnosis compared with those who did not experience OFR. The risk of OFR during AI treatment in breast cancer patients with chemotherapy-induced ovarian function failure is relevant, even beyond 45 years. Furthermore, women experiencing OFR had statistically significant higher estradiol levels during AI treatment (before OFR) than those without, with potential consequences regarding efficacy.


Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter.
N-myc down-regulated gene 1 (NDRG1/Cap43) is inducible by a variety of environmental stressors, including hypoxia. The present study identified a cis-acting element mediating the transactivation of the NDRG1 gene in murine RAW264.7 macrophage cells treated with hypoxia or deferoxamine, an iron chelator mimicking hypoxia. Through a series of deletions of the promoter of NDRG1 luciferase constructs, a minimal cis-acting element conferring inducibility by hypoxia and deferoxamine was localized to an early growth response 1 (Egr-1) and Sp1 overlapping binding site. Electrophoretic mobility shift assay, antibody supershift assay, and mutations of the Egr-1 binding site confirmed the specific binding of Egr-1 protein to this Egr-1/Sp1 motif. In addition, hypoxia increased the level of Egr-1 protein that correlated with induction of NDRG1 expression at both RNA and protein levels. Transient transfection of the Egr-1 gene into HeLa cells also resulted in up-regulation of the NDRG1 mRNA. The role of Egr-1 was further verified by mutations in the Egr-1 binding site, which reduced promoter inducibility by hypoxia and deferoxamine. Furthermore, the induction of NDRG1 expression by hypoxia and deferoxamine was diminished by RNA interference knockdown of Egr-1 gene expression and in Egr-1-/- mouse embryonic fibroblasts (MEF) compared with Egr-1+/- MEFs. These results showed for the first time that Egr-1 regulates NDRG1 transcription through an overlapping Egr-1/Sp1 binding site that acts as a major site of positive regulation of the NDRG1 promoter by hypoxia signaling.


Functional analysis of a retroviral host-range mutant: altered long terminal repeat sequences allow expression in embryonal carcinoma cells.
A retroviral host-range neomycin-resistant myeloproliferative sarcoma virus mutant, which is expressed in the embryonal carcinoma cell lines F9 and PCC4aza1R, was molecularly cloned and analyzed. This mutant virus, PCMV, differs from myeloproliferative sarcoma virus by two major deletions, one of which spans exactly a 75-base-pair repeat of the long terminal repeat. Functional analysis of recombinant viruses shows that the host-range expansion of PCMV is a property of nucleotide changes within the U3 region of the long terminal repeat. Furthermore, expression assays of chimeric long terminal repeats show that the enhancer region of PCMV joined to the promoter region of Moloney murine leukemia virus is sufficient to direct the synthesis of chloramphenicol acetyltransferase in F9 and PCC4 cells.


Longitudinal cerebral perfusion decrease in mild alzheimer's disease revealed by SPECT with statistical parametric mapping method.
Fifteen patients with mild Alzheimer's disease received baseline and follow-up technetium-99m hexamethylpropylene amine oxime SPECT examinations paired with neuropsychological assessments, including the Cognitive Ability Screening Instruments (CASI). The differences between baseline and follow-up SPECT images were analyzed by the voxel-based paired t test of the statistical parametric mapping technique. A simple regression analysis was also conducted to analyze the correlation between CASI sub-scores and both sets of SPECT images. In comparison with baseline images, cerebral perfusion at follow-up was significantly reduced in the left superior and middle temporal gyri, right middle and inferior temporal gyri, and right fusiform gyrus. A significant correlation was demonstrated between the list-generating fluency CASI sub-score and perfusion of the left fusiform gyrus. The visual construction sub-score was significantly correlated with perfusion of the right superior and medial frontal gyri.


Collaborative regression.
We consider the scenario where one observes an outcome variable and sets of features from multiple assays, all measured on the same set of samples. One approach that has been proposed for dealing with these type of data is "sparse multiple canonical correlation analysis" (sparse mCCA). All of the current sparse mCCA techniques are biconvex and thus have no guarantees about reaching a global optimum. We propose a method for performing sparse supervised canonical correlation analysis (sparse sCCA), a specific case of sparse mCCA when one of the datasets is a vector. Our proposal for sparse sCCA is convex and thus does not face the same difficulties as the other methods. We derive efficient algorithms for this problem that can be implemented with off the shelf solvers, and illustrate their use on simulated and real data.


High-fat diet aggravates 2,2',4,4'-tetrabromodiphenyl ether-inhibited testosterone production via DAX-1 in Leydig cells in rats.
Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2',4,4'-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown. In male rats treated with BDE47 by gavage for 12 weeks, the HFD significantly increased the BDE47 content of the liver and testis and increased the weight of the adipose tissue; increased macrovesicular steatosis in the liver and the levels of triglycerides, fasting glucose and insulin; further aggravated the disruption of the seminiferous epithelium; and lowered the level of testosterone, resulting in fewer sperm in the epididymis. Of note, the HFD enhanced BDE47-induced DAX-1 expression and decreased the expression levels of StAR and 3β-HSD in the testicular interstitial compartments in rats. In isolated primary Leydig cells from rats, BDE47 or insulin increased DAX-1 expression, decreased the expression of StAR and 3β-HSD, and reduced testosterone production, which was nearly reversed by knocking down DAX-1. These results indicated that the HFD aggravates BDE47-inhibited testosterone production through hyperinsulinemia, and the accumulation of testicular BDE47 that induces the up-regulation of DAX-1 and the subsequent down-regulation of steroidogenic proteins, i.e., StAR and 3β-HSD, in Leydig cells.


Ebp1 regulates myogenic differentiation of myoblast cells via SMAD2/3 signaling pathway.
Regulation of skeletal muscle development requires many of the regulatory networks that are fundamental to developmental myogenesis. ErbB3 binding protein-1 (Ebp1) is involved in the control of myoblasts development in chicken. However, the expression and biological functions of Ebp1 in the progress of myogenesis are unclear. This study focused on determining the effect of Ebp1 on myogenic proliferation and differentiation using a primary myoblasts culture model. Ebp1 was found to upregulate in proliferating myoblasts and decrease at the early stage of myogenic differentiation. The level of endogenous Ebp1 increased from E9 to E20 chicken leg muscles. Knockdown of Ebp1 had no effect on myoblasts proliferation. However, myogenic differentiation into multinucleated myotubes was significantly reduced. The mRNA and protein expression of MRFs was decreased when Ebp1 was knocked down. Downregulation of Ebp1, accompanied by elevated levels of pSMAD2/3, suggests that Ebp1 is involved in regulating myogenic differentiation via SMAD2/3 inhibition. The phosphorylation of SMAD2/3 was activated and the expression of MYOD and MYOG was reduced in Ebp1 knockdown myoblasts, but addition of LY2109761 (an inhibitor specified to SMAD2/3) blocked these effects. Collectively, these results indicate that Ebp1 promotes myoblast differentiation by inhibition of SMAD2/3 signaling pathway during chicken myogenesis. These data provide new insights into the biological role of Ebp1 in embryonic chicken skeletal muscle development.


Efficacy of catheter ablation for atrial fibrillation in patients with a permanent pacemaker for atrioventricular block.
Catheter ablation has been established to be an effective therapy for drug-refractory paroxysmal AF and is recommended as the treatment of choice for many patients, including those with a permanent pacemaker (PM). However, the clinical efficacy of catheter ablation of paroxysmal AF in patients with a permanent PM for atrioventricular block (AVB) is not clear. Twenty-nine patients with a permanent PM for AVB (AVB + PM group), and 145 age- and gender-matched control patients (on a 1:5 basis) without AVB and without a permanent PM (no-AVB + no-PM group), were included in this study. Atrial fibrillation (AF) recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 seconds beyond 3 months after catheter ablation in the absence of any antiarrhythmic treatment. During a mean follow-up period of 14.2 ± 8.6 months (range, 3-30 months), 54 patients (31.0%) developed recurrence of AF. The recurrence rate was higher in the AVB + PM group than in the no-AVB + no-PM group (48.3% versus 27.6%, P = 0.005). Cox regression analysis with adjustment for age, valvular heart disease, AVB and a PM together, left atrial (LA) diameter and PV isolation identified LA diameter (hazard ratio 1.054, 95% confidence interval 1.001-1.110, P = 0.047) and AVB and a PM together (hazard ratio 2.095, 95% confidence interval 1.109-3.960, P = 0.023) as two independent predictors of recurrence of AF. Patients with a permanent PM for AVB were at an increased risk of recurrence of AF after catheter ablation.


[Role of phospholipase C-gamma1 signaling pathway in H(2)O(2)-induced apoptosis of PC12 cells].
To explore the role of phospholipase C-gamma1 (PLC-gamma1) signaling pathway in H(2)O(2)-induced apoptosis of PC12 cells. PC12 cells were exposed to 50 micromol/L H(2)O(2) after pretreatment with 10 micromol/L U73122, a specific PLC-gamma1 inhibitor. Hoechst/PI double staining was performed to observe the morphological changes of the cells under light microscope. MTT assay was used to evaluate the cell viability, and the percentage of apoptotic cells was analyzed by flow cytometry. DNA fragmentation assay was carried out to characterize the cell apoptosis. After inhibition of the PLC-gamma1 signaling pathway with 10 micromol/L U73122, PC12 cells showed obvious apoptotic morphology, the viable cells decreased significantly, and the percentage of apoptotic cells rose to 35.7%. PC12 cells treated with U73122 presented with a distinct DNA ladder on electrophoresis resulting from DNA cleavage in the apoptotic cells. PLC-gamma1 signaling pathway plays an important protective role in H(2)O(2)-induced PC12 cell apoptosis.


Divalproex in the management of neuropsychiatric complications of remote acquired brain injury.
A retrospective chart review was conducted on 11 patients with a remote history of acquired brain injury (ABI) referred for psychiatric treatment who were treated with divalproex sodium alone or in combination with other psychotropic medications. The patients were highly heterogeneous. They had a variety of psychiatric symptoms and frequently received concomitant psychotropic medications. The mean daily dose of divalproex was 1,818+/-791 mg/day, serum valproic acid level 85.6+/-29.6 microg/ml. Mean Clinical Global Impression improvement score was 1.9+/-0.5. This is the largest postacute case series reported. It demonstrates that divalproex sodium is well tolerated and effective in reducing a broad range of neurobehavioral symptoms in psychiatric patients with a remote history of ABI.


Extreme Dynamics in the BamA β-Barrel Seam.
BamA is an essential component of the β-barrel assembly machine (BAM) that is responsible for insertion and folding of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria. BamA is an OMP itself, and its β-barrel transmembrane domain is thought to catalyze OMP insertion and folding, although the molecular mechanism remains poorly understood. Crystal structures of BamA and complementary molecular dynamics simulations have shown that its β-barrel seam (the interface between the first and last barrel strands) is destabilized. This has led to mechanistic models in which the BamA barrel seam functions as a lateral gate that opens and successively accepts β-hairpins from a nascent OMP such that a nascent barrel can bud from BamA. Consistent with this model, disulfide locking of the BamA barrel seam is lethal in Escherichia coli. Here we show that disulfide locking of the BamA barrel has no effect on its ability to catalyze folding of a model OMP into liposomes. However, disulfide trapping experiments indicate that the BamA barrel is highly dynamic in the liposome membranes, with the β-strands at the barrel seam undergoing "register sliding" by more than 14 Å both up and down the membrane. Remarkably, these extreme dynamics were also observed in the BamA barrel in the context of the native E. coli outer membrane. These results are consistent with a model in which the BamA barrel dynamics induce defects in the outer membrane that facilitate insertion of nascent OMPs.


AchievemenT of target resting HEart rate on beta-blockers in patients with stable angiNA and hypertension (ATHENA) in routine clinical practice in Russia.
The primary objective of this study was to establish the proportion of patients with stable angina and arterial hypertension on beta-blocker (BB) treatment reaching target resting heart rates (RHR) of 55-60 beats per min in clinical cardiology and general practice in Russia. Secondary objectives included the association between achievement of target RHR and mean BB doses, Seattle Angina Questionnaire (SAQ) scores and achievement of target blood pressure (BP) levels (systolic/diastolic BP <140/90 mmHg). ATHENA (AchievemenT of target resting HEart rate on beta-blockers in patients with stable angiNA and hypertension) was a non-interventional, cross-sectional, observational study conducted in 20 sites in Russia (NCT01321242). The study population comprised patients aged ≥18 years with stable angina (class I-III) and primary hypertension, on BB treatment for ≥2 months prior to enrollment. Of 399 study participants, 62 (15.5%; 95% confidence interval [CI]: 0.121 to 0.195) achieved target RHR. Clinical characteristics associated with significant differences between subgroups achieving and not achieving target RHR were systolic BP (131.1 vs 138.2 mmHg, P = 0.006), diastolic BP (78.6 vs 83.5 mmHg, P < 0.001) and frequency of nitroglycerin administration (1.5% vs 3.0%, P = 0.045). Most patients were taking bisoprolol (48.9%) and metoprolol (36.1%), with mean daily doses of 5.5 mg and 73.7 mg, respectively. Median SAQ scores were: 52.8 physical limitation, 50.0 angina stability, 60.0 angina frequency, 75.0 treatment satisfaction, 50.0 disease perception (quality of life) and 59.6 total score, with no significant differences between subgroups. Patients achieving target RHR were significantly more likely also to achieve target BP, compared with patients not achieving target RHR (72.6% vs 53.4%; P = 0.005; odds ratio: 2.309; 95% CI: 1.270 to 4.197). In a Russian population with stable angina and hypertension on BB treatment, RHR control was suboptimal. ClinicalTrials.gov identifier: NCT01321242.


Amyloidosis at Groote Schuur Hospital, Cape Town.
The records of 52 patients with amyloidosis admitted to Groote Schuur Hospital, Cape Town, between January 1969 and August 1982 were analysed. The male: female ratio was 1,3:1 and the mean age was 49,3 years. Forty-eight per cent of the patients had secondary amyloidosis, 21% had primary amyloidosis, 11,5% had localized amyloidosis and 11,5% had amyloidosis associated with multiple myeloma. Tuberculosis, chronic pulmonary sepsis and other chronic infections were present in 88% and rheumatoid arthritis in 16% of the patients with secondary amyloidosis. The commonest features at diagnosis were proteinuria (70%), oedema (52%) and hepatomegaly (39%). The diagnosis of amyloidosis was established by renal, liver and rectal biopsy (either singly or in combination) in 82% of cases. The prevalence of amyloidosis at autopsy was 0,28%.


Organisational barriers to thrombolysis treatment of acute ischaemic stroke.
Intravenous thrombolysis with fibrinolytic drugs such as alteplase is not implemented widely in any country although the treatment is both effective and cost-effective in selected patients within a 3-h window after acute ischaemic stroke. The purpose of the present study was to describe the organisational barriers to delivery of thrombolysis for acute ischaemic stroke with special regard to the Danish healthcare system. Systematic and unsystematic searches of medical, economic and grey literature on organisational barriers to thrombolysis treatment were performed in Cochrane, PubMed, EMBASE, Cinahl, Econlit, NHS EED, SvedMed+ and the Health Technology Assessment (HTA) database. The search periods were 1996-2006. Three main types of literature on organisational barriers were found: medical literature including HTA reports on barriers related to the 3-h window, economic literature on barriers related to the lack of capacity to provide the treatment on a 24-h basis, and grey literature/policy papers on standards and demands to the hospitals and healthcare systems who implements the treatment. Information on organisational barriers can be extracted from different types of literature (medical, economic and grey literature/policy papers), but organisational barriers are most often not the primary study objective in the relevant literature. This review showed a broad spectrum of possible organisational barriers to the delivery of thrombolysis treatment of acute ischaemic stroke.


Different expression of procoagulant activity in macrophages associated with experimental and human tumors.
Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of human and experimental tumors, might contribute to fibrin deposition within malignant tissues through the production of procoagulant activity (PCA). Recent studies in different types of experimental tumors and in some cancer patients indicate that the functional status in terms of PCA of mononuclear phagocytes at 'peripheral' sites is not the same as that of macrophages at the tumor site (tumor-associated macrophages, TAM). Peripheral blood monocytes and/or peritoneal macrophages from V2-carcinoma-bearing rabbits and from mice bearing different types of tumors, like cells from normal animals, have low levels of basal PCA and are able to respond with a marked increase in PCA to in vitro stimulation. Likewise, in patients with primary lung cancer, pulmonary alveolar macrophages (PAM) obtained from the contralateral side of the neoplasm and blood monocytes behave essentially as cells from normal individuals. In contrast, profound changes in PCA have been found in TAM. In some experimental tumors and in a number of the patients, macrophages taken at the tumor site express high levels of basal PCA, which most probably reflect in vivo activation. Local activation of macrophages for PCA production might contribute to fibrin deposition at the tumor site. In the other experimental tumors studied and in the remaining patients, not only have macrophages low basal PCA but they also fail to respond to various stimulants in vitro. Although the mechanisms underlying these changes and their pathophysiological significance remain to be established, it is apparent that neoplastic growth may modulate the expression of macrophage PCA at the tumor site.(ABSTRACT TRUNCATED AT 250 WORDS)


Effective Prevention for Portal Venous System Thrombosis After Splenectomy: A Meta-Analysis.
Portal venous system thrombosis (PVST) is a common and potentially life-threatening complication of splenectomy for portal hypertension due to cirrhosis. A meta-analysis was conducted to study the necessity of pharmacologic prophylaxis of PVST after splenectomy and how to select the feasible treatment method. Articles were searched through the PubMed, EMBASE, Cochrane Library databases, and CNKI. Overall, 404 articles were initially identified, and 11 of them were eligible. Among these selected articles, 7 articles were associated with the necessity of anticoagulation for prevention of PVST, while 5 were about the drug selection. We first demonstrated that the incidence of PVST after splenectomy was significantly lower in patients who received the preventive measures than in those who did not (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.13-0.39, P < .00001). Then, we compared the new-style treatment with the conventional treatment and found that patients with new therapy method had lower incidence of PVST than those who received conventional treatment (OR: 0.37, 95% CI: 0.27-0.51, P < .00001). Also, some studies (n = 4) reported that early and combination use of anticoagulation drugs can lead to better outcome for patients with splenectomy and devascularization. Preventative use of anticoagulant drugs might decrease the incidence of PVST after splenectomy in patients with portal hypertension, new anticoagulant drugs such as low-molecular-weight heparin should be used, and early or combination use of anticoagulation drugs might lead to lower PVST incidence for patients.


Terminal repeat retrotransposons as DNA markers in fungi.
In this study, we demonstrate that ClIRAP primers designed using the transposable element RetroCl1 sequence from Colletotrichum lindemuthianum can be used to generate an efficient IRAP (inter-retrotransposon amplified polymorphism) molecular marker to study intra- and inter-species diversity in fungi. It has been previously demonstrated that primers generated from this TRIM-like element can be used in the Colletotrichum species. We now prove that the RetroCl1 sequence can also be used to analyze diversity in different fungi. IRAP profiles were successfully generated for 27 fungi species from 11 different orders, and intra-species genetic variability was detected in six species. The ClIRAP primers facilitate the use of the IRAP technique for a variety of fungi without prior knowledge of the genome.


Propranolol treatment lowers blood pressure, reduces vascular inflammatory markers and improves endothelial function in obese mice.
Obesity-associated hypertension is accompanied by a number of cardiovascular risk factors including vascular insulin resistance (IR) and higher sympathetic nervous activity. Therefore, autonomic blockade was demonstrated to reverse hypertension, endothelial dysfunction and IR in obese individuals. We hypothesized that β-AR blockade with propranolol would restore endothelial function and vascular insulin signaling in obesity, associated with an anti-inflammatory effect. Body weight, systolic blood pressure (SBP), plasma biochemical parameters and aortic endothelial function were analyzed in mice fed standard diet (control group) or a high fat diet (HFD) that were treated with vehicle (water) or propranolol (10mg/kg/day) for 8weeks. Propranolol treatment did not modify obesogenic effect of HFD feeding. However, propranolol was effective in preventing the rise in SBP, the hyperinsulinemia and the impaired endothelium-dependent relaxation to acetylcholine and to insulin in obese mice. Protective effect of propranolol administration in endothelial function was associated with increased nitric oxide (NO) production and phosphorylation of Akt (Ser473) and eNOS (Ser1177), but with reduced phospho-IRS-1(Ser307) and phospho-ERK1/2 (Thr202/Tyr204). In addition, β-blocker propranolol prevented the NF-kB nuclear translocation and the increase in phospho-IκB-α (Ser32) and in interleukin(IL)-6 expression in aorta of obese mice, without significant changes in either aortic reactive oxygen species production or in circulating IL-6 and TNF-α levels. In β2-AR knockout mice, despite increasing body weight and visceral fat, HFD did not increase SBP and showed a partial improvement of endothelial function, revealing a role of β2-AR in cardiovascular effects of obesity. In conclusion, our results suggest that β-AR blockade with propranolol is effective to prevent the endothelial dysfunction, vascular IR and pro-inflammatory state displayed in HFD-induced obesity, independent of changes in body weight.


Seeing gray when feeling blue? Depression can be measured in the eye of the diseased.
Everyday language relates depressed mood to visual phenomena. Previous studies point to a reduced sensitivity of subjective contrast perception in depressed patients. One way to assess visual contrast perception in an objective way at the level of the retina is to measure the pattern electroretinogram (PERG). To find an objective correlate of reduced contrast perception, we measured the PERG in healthy control subjects and unmedicated and medicated patients with depression. Forty patients with a diagnosis of major depression (20 with and 20 without medication) and 40 matched healthy subjects were studied. Visual PERGs were recorded from both eyes. Unmedicated and medicated depressed patients displayed dramatically lower retinal contrast gain. We found a strong and significant correlation between contrast gain and severity of depression. This marker distinguishes most patients on a single-case basis from control subjects. A receiver operating characteristic analysis revealed a specificity of 92.5% and a sensitivity of 77.5% for classifying the participants correctly. Because PERG recording does not depend on subjective ratings, this marker may be an objective correlate of depression in human beings. If replicated, PERG may be helpful in further animal and human research in depression.


MUSCULAR SUBAORTIC STENOSIS: THE EFFECT OF PERIPHERAL VASODILATATION.
Amyl nitrite was administered on two occasions to a patient with muscular subaortic stenosis, to ascertain if selective peripheral vasodilatation would affect the degree of obstruction to left ventricular outflow in this condition. On each occasion there was a marked increase in the systolic pressure gradient across the left ventricular outflow tract prior to the onset of reflex tachycardia. Following the second amyl nitrite inhalation, the systolic cross-sectional area of the left ventricular outflow tract decreased to 1.0 sq. cm., from the control value of 2.6 sq. cm. It is believed that the increased degree of muscular subaortic stenosis, following peripheral vasodilatation, could be secondary to a decrease in the systolic size of the whole left ventricle, or to a selective decrease in the physical size of the left ventricular outflow tract.


Photon-Number-Resolved Measurement of an Exciton-Polariton Condensate.
We measure the full photon-number distribution emitted from a Bose condensate of microcavity exciton polaritons confined in a micropillar cavity. The statistics are acquired by means of a photon-number-resolving transition edge sensor. We directly observe that the photon-number distribution evolves with the nonresonant optical excitation power from geometric to quasi-Poissonian statistics, which is canonical for a transition from a thermal to a coherent state. Moreover, the photon-number distribution allows one to evaluate the higher-order photon correlations, shedding further light on the coherence formation and phase transition of the polariton condensate. The experimental data are analyzed in terms of thermal-coherent states, which gives direct access to the thermal and coherent fraction from the measured distributions. These results pave the way for a full understanding of the contribution of interactions in light-matter condensates in the coherence buildup at threshold.


Magnetic Resonance Imaging Patterns of Post-Operative Spinal Infection: Relationship between the Clinical Onset of Infection and the Infection Site.
To investigate the magnetic resonance imaging (MRI) findings and the patterns of postoperative spinal infection according to the passage of time. Institutional review board approval was obtained, and informed consent was not obtained for the retrospective review of patients' medical records. A total of 43 patients (27 men and 16 women; mean age, 64) diagnosed with postoperative spinal infection were included in this study. We retrospectively reviewed the MRI findings and the medical records and categorized the infection sites based on MRI, i.e., anterior, posterior, and both parts. The duration of the clinical onset from surgery was divided, i.e., acute (≤2 weeks), subacute (2-4 weeks), and late (>4 weeks). Postoperative spinal infection was involved in the posterior part in 31 (72%), anterior part in two (4.7%), and both parts in 10 patients (23.3%). Abscess or phlegmon in the back muscles and laminectomy site were the most common MRI findings. The number of patients with acute, subacute, and late clinical onset were 35, two, and six, respectively (mean, 33.4 days; range, 1-730 days). The mean duration of the clinical onset was 12 days in the posterior part, 15.2 days in both parts, and 456.5 days in the anterior part. Postoperative spinal infection usually occurred within four weeks in the posterior part and over time the infection was considered to spread into the anterior part. For the evaluation of postoperative spinal infection, the posterior surgical field was more important than the vertebral body or the disc space on MRI.


Effect of interferon preparations on the uptake of non-opsonized Escherichia coli by mouse peritoneal macrophages.
Uptake of non-opsonized Escherichia coli by mouse peritoneal macrophages (MPM) is influenced by pre-treatment of MPM with homologous interferon preparations. Incubation of MPM with 10(2)-10(3) units of interferon per ml for 18 hours resulted in a 30-70 per cent increase in the phagocytosis rate as well as maximal phagocytic capacity. This effect was time dependent. At least seven hours of interferon pre-treatment and a phagocytosis period of 90 minutes were necessary for a statistically significant increase of the phagocytosis. Treatment of MPM with high concentrations of interferon (i.e. more than 10(4) units per ml) had a depressive effect on the phagocytosis. Both the enhancing and the depressive effects were characterized by the standard physico-chemical properties of interferons. Both effects were species specific. The phagocytosis enhancing effect was neutralized by anit-interferon serum.


Efficacy of three ELISA measurements of anti-cyclic citrullinated peptide antibodies in the early diagnosis of rheumatoid arthritis.
The objective of the present study was to determine the efficacy of anti-cyclic citrullinated peptide (anti-CCP) antibody detection in the early diagnosis of rheumatoid arthritis (RA), as well as to compare three commercially available enzyme-linked immunosorbent assay (ELISA) kits used to detect such antibodies. We analysed the presence of anti-CCP antibodies in the sera of 78 patients who had been newly referred from primary healthcare centres to the Early Polyarthritis Unit. We also included in the study a group of 50 healthy controls. None of the patients had previously received treatment for the disease. After 1-year follow-up, the diagnosis of RA was confirmed in 53 of these patients. The ELISA kits under study were IMMUNOSCAN RA (Euro-Diagnostica AB), QUANTA Lite CCP IgG ELISA (INOVA Diagnostic) and DIA-STAT Anti-CCP (Axis-Shield Diagnostics); the sensitivity obtained was 52.8%, 58.5% and 52.8%, respectively, with 100% specificity for all three kits. Anti-CCP antibodies detected the presence of RA in 26% of patients without positive rheumatoid factor (RF). The sum of anti-CCP antibodies or the presence of RF gave a sensitivity of up to 67%, with specificity ranging between 94 and 97%. Anti-CCP antibodies show high specificity for the diagnosis of RA. The three ELISAs analysed offer the same degree of diagnostic accuracy.


Identification of differentially expressed circular RNAs in human colorectal cancer.
Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.


Enhanced Adsorption of Zn(II) onto Graphene Oxides Investigated Using Batch and Modeling Techniques.
Graphene oxide (GO) was synthesized and employed as an adsorbent for Zn(II) removal from an aqueous solution. The adsorption isotherms showed that Zn(II) adsorption can be better described using the Freundlich model than the Langmuir model. The maximum adsorption capacity of Zn(II) on GO determined using the Langmuir model at pH 7.0 and 293 K was 208.33 mg/g. The calculation of thermodynamic parameters revealed that the process of Zn(II) adsorption on GO was chemisorptions, endothermic, and spontaneous. Kinetic studies indicated that the pseudo-second-order kinetic model showed a better simulation of Zn(II) adsorption than the pseudo-first-order kinetic model. On the basis of surface complexation modeling, the double layer model provided a satisfactory prediction of Zn(II) by inner-sphere surface complexes (for example, SOZn⁺ and SOZnOH species), indicating that the interaction mechanism between Zn(II) and GO was mainly inner-sphere complexation. In terms of reusability, GO could maintain 92.23% of its initial capability after six cycles. These findings indicated that GO was a promising candidate for the immobilization and preconcentration of Zn(II) from aqueous solutions.


Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts.
Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.


Blast injuries to the lung: epidemiology and management.
Lung injury is frequently a component of the polytrauma sustained by military personnel surviving blast on the battlefield. This article describes a case series of the military casualties admitted to University Hospital Birmingham's critical care services (role 4 facility), during the period 1 July 2008 to 15 January 2010. Of the 135 casualties admitted, 107 (79.2%) were injured by explosive devices. Plain chest films taken soon after arrival in the role 4 facility were reviewed in 96 of the 107 patients. In 55 (57.3%) films a tracheal tube was present. One or more radiological abnormalities was present in 66 (68.75%) of the films. Five patients met the consensus criteria for the definition of adult respiratory distress syndrome (ARDS). The majority of casualties with blast-related lung injury were successfully managed with conventional ventilatory support employing a lung protective strategy; only a small minority received non-conventional support at any time in the form of high-frequency oscillatory ventilation. Of those casualties who survived to be received by the role 4 facility, none subsequently died as a consequence of lung injury.


Major depressive disorder treatment guidelines in Japan.
Japanese treatment guidelines, consensus guidelines, and treatment algorithms for managing patients with major depressive disorder (MDD) have been developed and/or updated in the past decade. The treatment guidelines, which are evidence-based, are the most detailed of the 3 types of guidance; they describe how to establish a treatment plan, treatment methods, and special problems such as intractable depression and suicide. The Japanese consensus guidelines were compiled from the results of a survey about treatment choices in MDD that was sent to members of the Japanese Society of Psychiatry and Neurology. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were the most common first-line treatments, followed by tricyclic antidepressants and tetracyclic antidepressants. The consensus guidelines are not evidence-based but are practical and easy to use. The Japanese treatment algorithm for MDD is a flowchart created in conjunction with the International Psychopharmacology Algorithm Project. The flowchart shows steps in treatment both for patients who respond to initial treatment and for those who need several trials of treatment. These 3 forms of guidance for managing patients with MDD in Japan are reviewed.


Commercial hybrids and mutant genotypes reveal complex protective roles for inducible terpenoid defenses in maize.
Plant defense research is facilitated by the use of genome-sequenced inbred lines; however, a foundational knowledge of interactions in commercial hybrids remains relevant to understanding mechanisms present in crops. Using an array of commercial maize hybrids, we quantified the accumulation patterns of defense-related metabolites and phytohormones in tissues challenged with diverse fungal pathogens. Across hybrids, Southern leaf blight (Cochliobolus heterostrophus) strongly elicited specific sesqui- and diterpenoid defenses, namely zealexin A4 (ZA4) and kauralexin diacids, compared with the stalk-rotting agents Fusarium graminearum and Colletotrichum graminicola. With respect to biological activity, ZA4 and kauralexin diacids demonstrated potent antimicrobial action against F. graminearum. Unexpectedly, ZA4 displayed an opposite effect on C. graminicola by promoting growth. Overall, a negative correlation was observed between total analyzed terpenoids and fungal growth. Statistical analyses highlighted kauralexin A3 and abscisic acid as metabolites most associated with fungal suppression. As an empirical test, mutants of the ent-copalyl diphosphate synthase Anther ear 2 (An2) lacking kauralexin biosynthetic capacity displayed increased susceptibility to C. heterostrophus and Fusarium verticillioides. Our results highlight a widely occurring defensive function of acidic terpenoids in commercial hybrids and the complex nature of elicited pathway products that display selective activities on fungal pathogen species.


[The role of apoptosis during craniofacial development: concepts and importance in pathology].
Apoptosis is an essential common final pathway in numerous pathological conditions such as malignant tumors, HIV-related CD4 lymphocytes degeneration, neurodegenerative disorders, and in programmed cell death events during normal embryogenesis. Some teratogenic substances for man and laboratory mammals induce an increase of the apoptotic phenomenon, responsible for the occurrence of some precise cranio-maxillo-facial malformations. The study of cell death during normal or teratogenic embryonic development allows to analyse the cellular mechanisms implied in the control of the apoptotic phenomenon, together with its dysregulation ending in pathological processes. We review the cell death phenomenon during cephalogenesis, both during normal embryogenesis, or in teratogenic conditions known to induce cranio-maxillo-facial malformations.