Cross-cultural adaptation, reliability, and validity of the Turkish version of the obesity-specific quality of life questionnaire: quality of life, obesity, and dietetics (QOLOD) rating scale
Obesity is one of the main public health issues in many countries including Turkey. The aim of the study is to test cross-cultural adaptation, reliability, and validity of QOLOD rating scale in the Turkish language. This methodological study was conducted among the overweight and obesity people between February-March, 2018 in Ankara Atatürk Training and Research Hospital. The data was collected through self-report and face to face interviews. The QOLOD rating scale has 36 items, a 5-point Likert scale (1–5) is used for each question. In the study, of the 180 participants, 101 (56.1%) were female, 79 (43.9%) were male, and the mean age was 43.36 ± 14.28 (min-max 18–87) years. According to the CFA, the Turkish version of QOLOD rating scale shows a multidimensional structure consisting of 34 items. Two items (item 11 and item 35) were excluded from the scale according to the CFA. Cronbach's Alpha value changes between 0.927–0.930. Finding shows that the Turkish version of QOLOD rating scale had sufficient validity and reliability for Turkish population, had strong psychometric characteristics.


Rapid metal ions shuttling through 1,3-alternate Thiacalix[4]crown tubes.
Several new thiacalix[4]monocrown and thiacalix[4]biscrown compounds were synthesized. Their metal ion extractabilities are found to be lower than those of conventional calix[4]crowns. By use of X-ray crystal structures and (1)H NMR spectroscopy, this result is explained by weaker electrostatic interactions of the polyether ring oxygen atoms with the metal ions and diminished pi-metal ion interactions between the metal ions and the aromatic rings of the thiacalix[4]crowns. Temperature-dependent (1)H NMR spectroscopic measurements reveal coalescence temperatures T(c)(intra) and T(c)(inter) for metal ion exchange. In one case, this exchange was rationalized as metal ion shuttling through a thiacalix[4]biscrown tube. Since the metal ions are less tightly complexed by the polyether units in thiacalix[4]biscrowns than in conventional calix[4]biscrowns, more facile metal ion exchange between the two polyether units takes place in the former.


Comparison of statistical approaches to predicting norovirus laboratory reports before and during COVID-19: insights to inform public health surveillance.
Social distancing interrupted transmission patterns of contact-driven infectious agents such as norovirus during the Covid-19 pandemic. Since routine surveillance of norovirus was additionally disrupted during the pandemic, traditional naïve forecasts that rely only on past public health surveillance data may not reliably represent norovirus activity. This study investigates the use of statistical modelling to predict the number of norovirus laboratory reports in England 4-weeks ahead of time before and during Covid-19 pandemic thus providing insights to inform existing practices in norovirus surveillance in England. We compare the predictive performance from three forecasting approaches that assume different underlying structure of the norovirus data and utilized various external data sources including mobility, air temperature and relative internet searches (Time Series and Regularized Generalized Linear Model, and Quantile Regression Forest). The performance of each approach was evaluated using multiple metrics, including a relative prediction error against the traditional naive forecast of a five-season mean. Our data suggest that all three forecasting approaches improve predictive performance over the naïve forecasts, especially in the 2020/21 season (30-45% relative improvement) when the number of norovirus reports reduced. The improvement ranged from 7 to 22% before the pandemic. However, performance varied: regularized regression incorporating internet searches showed the best forecasting score pre-pandemic and the time series approach achieved the best results post pandemic onset without external data. Overall, our results demonstrate that there is a significant value for public health in considering the adoption of more sophisticated forecasting tools, moving beyond traditional naïve methods, and utilizing available software to enhance the precision and timeliness of norovirus surveillance in England.


Updating the evidence relating to physical activity intervention studies in older people.
For older adults, physical activity (PA) plays a central role in the prevention and management of chronic disease, and has the potential to reduce physical decline, maintain functional ability and prevent injuries. This review provides an update of the evidence relating to the effectiveness of PA intervention studies (both general PA and trials specific to progressive resistance training (PRT)) for older adults. The following electronic databases were searched for articles published since 1999: Medline, PubMed, EMBASE, CINAHL and Sport Discus. For the PRT section, a 2002 Cochrane review was also used. Eight general PA intervention studies were included in this review, ranging from one-on-one counselling in general practice to the community-wide promotion of walking. The aim of most of the trials was to increase moderate and/or vigorous activity levels. Most of the studies reviewed had some degree of success in getting older people to be more active. However, a major limitation was the use of self-report measures of PA. The review of PRT interventions included 21 trials. Participants in half the studies had either functional limitations or a chronic condition. Most trials were conducted in a supervised setting using specialised equipment. Increased strength and improvement in basic functional tasks were generally reported, but there was a paucity of strong evidence linking PRT with reduced physical disability and improved health-related quality of life. While considerable progress is being made in this area, further population-based studies that include home and whole-community interventions are required.


Structural studies of Proteus mirabilis catalase in its ground state, oxidized state and in complex with formic acid.
The structure of Proteus mirabilis catalase in complex with an inhibitor, formic acid, has been solved at 2.3 A resolution. Formic acid is a key ligand of catalase because of its ability to react with the ferric enzyme, giving a high-spin iron complex. Alternatively, it can react with two transient oxidized intermediates of the enzymatic mechanism, compounds I and II. In this work, the structures of native P. mirabilis catalase (PMC) and compound I have also been determined at high resolution (2.0 and 2.5 A, respectively) from frozen crystals. Comparisons between these three PMC structures show that a water molecule present at a distance of 3.5 A from the haem iron in the resting state is absent in the formic acid complex, but reappears in compound I. In addition, movements of solvent molecules are observed during formation of compound I in a cavity located away from the active site, in which a glycerol molecule is replaced by a sulfate. These results give structural insights into the movement of solvent molecules, which may be important in the enzymatic reaction.


A small CDC25 dual-specificity tyrosine-phosphatase isoform in Arabidopsis thaliana.
The dual-specificity CDC25 phosphatases are critical positive regulators of cyclin-dependent kinases (CDKs). Even though an antagonistic Arabidopsis thaliana WEE1 kinase has been cloned and tyrosine phosphorylation of its CDKs has been demonstrated, no valid candidate for a CDC25 protein has been reported in higher plants. We identify a CDC25-related protein (Arath;CDC25) of A. thaliana, constituted by a sole catalytic domain. The protein has a tyrosine-phosphatase activity and stimulates the kinase activity of Arabidopsis CDKs. Its tertiary structure was obtained by NMR spectroscopy and confirms that Arath;CDC25 belongs structurally to the classical CDC25 superfamily with a central five-stranded beta-sheet surrounded by helices. A particular feature of the protein, however, is the presence of an additional zinc-binding loop in the C-terminal part. NMR mapping studies revealed the interaction with phosphorylated peptidic models derived from the conserved CDK loop containing the phosphothreonine-14 and phosphotyrosine-15. We conclude that despite sequence divergence, Arath;CDC25 is structurally and functionally an isoform of the CDC25 superfamily, which is conserved in yeast and in plants, including Arabidopsis and rice.


Differential pain modulation properties in central neuropathic pain after spinal cord injury.
It seems that central neuropathic pain (CNP) is associated with altered abilities to modulate pain; whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution, enhanced pain excitation is associated with the intensity of chronic pain. We investigated the hypothesis that CNP is associated with decreased descending pain inhibition along with increased neuronal excitability and that both traits are associated with spinothalamic tract (STT) damage. Chronic spinal cord injury subjects with CNP (n = 27) and without CNP (n = 23) and healthy controls (n = 20) underwent the measurement of pain adaptation, conditioned pain modulation (CPM), tonic suprathreshold pain (TSP), and spatial summation of pain above injury level. Central neuropathic pain subjects also underwent at and below-lesion STT evaluation and completed the questionnaires. Central neuropathic pain subjects showed decreased CPM and increased enhancement of TSP compared with controls. Among CNP subjects, the dysfunction of CPM and pain adaptation correlated positively with the number of painful body regions. The magnitude of TSP and spatial summation of pain correlated positively with CNP intensity. STT scores correlated with CNP intensity and with TSP, so that the more affected the STT below injury level, the greater the CNP and TSP magnitude. It seems that CNP is associated with altered abilities to modulate pain, whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution and enhanced pain excitation is associated with the intensity of chronic pain. Thus, top-down processes may determine the spread of CNP, whereas bottom-up processes may determine CNP intensity. It also seems that the mechanisms of CNP may involve STT-induced hyperexcitability. Future, longitudinal studies may investigate the timeline of this scenario.


Qualitative and quantitative differences in the immune response to foot-and-mouth disease virus antigens and synthetic peptides.
In cross-immunization studies using foot-and-mouth disease virus (FMDV) antigens and a synthetic peptide, from a region within virus coat protein VP1, it has been shown that intact virus will prime the immune system for intact virus, virus subunits and synthetic peptide but not for disrupted virus. In contrast, peptide will prime for a response to peptide and virus subunits but not to intact virus or disrupted virus. Furthermore, studies on antibody populations in anti-virus and anti-peptide antisera demonstrated clear differences in the nature of the antibody response to the two antigens. This result is reflected in protection studies carried out on animals immunized with virus particles or peptides where there is a clearer correlation between in vitro neutralization and protection in vivo following peptide immunization. Thus, it has been shown that there are major qualitative and quantitative differences in the immune response to the FMDV particle and synthetic peptide.


GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients.
GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.


Colander: a probability-based support vector machine algorithm for automatic screening for CID spectra of phosphopeptides prior to database search.
We developed a probability-based machine-learning program, Colander, to identify tandem mass spectra that are highly likely to represent phosphopeptides prior to database search. We identified statistically significant diagnostic features of phosphopeptide tandem mass spectra based on ion trap CID MS/MS experiments. Statistics for the features are calculated from 376 validated phosphopeptide spectra and 376 nonphosphopeptide spectra. A probability-based support vector machine (SVM) program, Colander, was then trained on five selected features. Data sets were assembled both from LC/LC-MS/MS analyses of large-scale phosphopeptide enrichments from proteolyzed cells, tissues and synthetic phosphopeptides. These data sets were used to evaluate the capability of Colander to select pS/pT-containing phosphopeptide tandem mass spectra. When applied to unknown tandem mass spectra, Colander can routinely remove 80% of tandem mass spectra while retaining 95% of phosphopeptide tandem mass spectra. The program significantly reduced computational time spent on database search by 60-90%. Furthermore, prefiltering tandem mass spectra representing phosphopeptides can increase the number of phosphopeptide identifications under a predefined false positive rate.


Osteopontin RNA aptamer can prevent and reverse pressure overload-induced heart failure.
Cardiac myocyte hypertrophy, the main compensatory response to chronic stress in the heart often progresses to a state of decompensation that can lead to heart failure. Osteopontin (OPN) is an effector for extracellular signalling that induces myocyte growth and fibrosis. Although increased OPN activity has been observed in stressed myocytes and fibroblasts, the detailed and long term effects of blocking OPN signalling on the heart remain poorly defined. Targeting cardiac OPN protein by an RNA aptamer may be beneficial for tuning down OPN pathologic signalling. We aimed to demonstrate the therapeutic effects of an OPN RNA aptamer on cardiac dysfunction. In vivo, we show that in a mouse model of pressure overload, treating at the time of surgeries with an OPN aptamer prevented cardiomyocyte hypertrophy and cardiac fibrosis, blocked OPN downstream signalling (PI3K and Akt phosphorylation), reduced expression of extracellular matrix (Lum, Col3a1, Fn1) and hypertrophy (Nppa, Nppb) genes, and prevented cardiac dysfunction. Treating at two months post-surgeries with the OPN aptamer reversed cardiac dysfunction and fibrosis and myocyte hypertrophy. While genetic homozygous deletion of OPN reduced myocardial wall thickness, surprisingly cardiac function and myocardial fibrosis, specifically collagen deposition and myofibroblast infiltration, were worse compared with wild type mice at three months of pressure overload. Taken together, these data demonstrate that tuning down cardiac OPN signalling by an OPN RNA aptamer is a novel and effective approach for preventing cardiac hypertrophy and fibrosis, improving cardiac function, and reversing pressure overload-induced heart failure.


Urine drug testing of chronic pain patients. II. Prevalence patterns of prescription opiates and metabolites.
This study of 20,089 urine specimens from chronic pain patients provided a unique opportunity to evaluate the prevalence of prescription opiates and metabolites, assess the usefulness of inclusion of normetabolites in the test panel, and compare opiate and oxycodone screening results to liquid chromatography with tandem mass spectrometry (LC-MS-MS) results. All specimens were screened by an opiate [enzyme-linked immunosorbent assay (ELISA), 100 ng/mL] and oxycodone assay [ELISA, 100 ng/mL or enzyme immunoassay (EIA), 50 ng/mL] and simultaneously tested by LC-MS-MS [limit of quantitation (LOQ) = 50 ng/mL] for 10 opiate analytes (codeine, norcodeine, morphine, hydrocodone, dihydrocodeine, norhydrocodone, hydromorphone, oxycodone, noroxycodone, and oxymorphone). Approximately two-thirds of the specimens were positive for one or more opiate analytes. The number of analytes detected in each specimen varied from 1 to 8 with 3 (34.8%) being most prevalent. Hydrocodone and oxycodone (in combination with metabolites) were most prevalent followed by morphine. Norcodeine was only infrequently detected whereas the prevalence of norhydrocodone and noroxycodone was approximately equal to the prevalence of the parent drug. A substantial number of specimens were identified that contained norhydrocodone (n = 943) or noroxycodone (n = 702) but not the parent drug, thereby establishing their interpretative value as biomarkers of parent drug use. Comparison of the two oxycodone screening assays revealed that the oxycodone ELISA had broader cross-reactivity with opiate analytes, and the oxycodone EIA was more specific for oxycodone. Specimens containing only norhydrocodone were best detected with the opiate ELISA whereas noroxycodone (only) specimens were best detected by the oxycodone EIA.


Vena cava presents endothelial dysfunction prior to thoracic aorta in heart failure: the pivotal role of nNOS uncoupling/oxidative stress.
Arterial endothelial dysfunction has been extensively studied in heart failure (HF). However, little is known about the adjustments shown by the venous system in this condition. Considering that inferior vena cava (VC) tone could influence cardiac performance and HF prognosis, the aim of the present study was to assess the VC and thoracic aorta (TA) endothelial function of HF-post-myocardial infarction (MI) rats, comparing both endothelial responses and signaling pathways developed. Vascular reactivity of TA and VC from HF post-MI and sham operated (SO) rats was assessed with a wire myograph, 4 weeks after coronary artery occlusion surgery. Nitric oxide (NO), H2O2 production and oxidative stress were evaluated in situ with fluorescent probes, while protein expression and dimer/monomer ratio was assessed by Western blot. VC from HF rats presented endothelial dysfunction, while TA exhibited higher acetylcholine (ACh)-induced vasodilation when compared with vessels from SO rats. TA exhibited increased ACh-induced NO production due to a higher coupling of endothelial and neuronal NO synthases isoforms (eNOS, nNOS), and enhanced expression of antioxidant enzymes. These adjustments, however, were absent in VC of HF post-MI rats, which exhibited uncoupled nNOS, oxidative stress and higher H2O2 bioavailability. Altogether, the present study suggests a differential regulation of endothelial function between VC and TA of HF post-MI rats, most likely due to nNOS uncoupling and compromised antioxidant defense.


Diuretics for respiratory distress syndrome in preterm infants.
Lung edema may complicate respiratory distress syndrome (RDS) in preterm infants. The aim of this review was to assess the risks and benefits of diuretic administration in preterm infants with RDS. We used the standard search method of the Cochrane Neonatal Review Group. We searched Medline, Embase and the Cochrane Controlled Trials Register from the Cochrane Library, using the following keywords: <exp respiratory distress syndrome> and <exp diuretics>. In addition, we searched the abstract books of the American Thoracic Society and Pediatric Research Societies. We only included trials in which preterm infants with RDS and less than 5 days of age were randomly allocated to diuretic administration. Of those trials, we only included studies in which at least one of the following outcomes measures was evaluated: mortality, patent ductus arteriosus, hypovolemic shock, intraventricular hemorrhage, renal failure, duration of oxygen supplementation, duration of mechanical ventilation, need for oxygen supplementation at 28 days of life, oxygen supplementation at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, number of rehospitalizations during the first year of life, and neurodevelopmental outcome. We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. Six studies met inclusion criteria. Studies available for this systematic review were all done before the current era of prenatal steroids, surfactant, indomethacin and fluid restriction. Furosemide administration had no long-term benefits. Furosemide-induced transient improvement in pulmonary function did not outweigh an increased risk for patent ductus arteriosus and for hemodynamic instability. There are no current data to support routine diuretic administration in preterm infants with RDS. Elective administration of furosemide or any diuretic to any patient with RDS should be carefully weighed against the risk of precipitating hypovolemia. In addition, elective administration of furosemide should be weighed against the risk of developing a symptomatic patent ductus arteriosus.


Accelerating Cartesian MRI by domain-transform manifold learning in phase-encoding direction.
This study developed a domain-transform framework comprising domain-transform manifold learning with an initial analytic transform to accelerate Cartesian magnetic resonance imaging (DOTA-MRI). The proposed method directly transforms undersampled Cartesian k-space data into a reconstructed image. In Cartesian undersampling, the k-space is fully or zero sampled in the data-acquisition direction (i.e., the frequency-encoding direction or the x-direction); one-dimensional (1D) inverse Fourier transform (IFT) along the x-direction on the undersampled k-space does not induce any aliasing. To exploit this, the algorithm first applies an analytic x-direction 1D IFT to the undersampled Cartesian k-space input, and subsequently transforms it into a reconstructed image using deep neural networks. The initial analytic transform (i.e., 1D IFT) allows the fully connected layers of the neural network to learn 1D global transform only in the phase-encoding direction (i.e., the y-direction) instead of 2D transform. This drastically reduces the number of parameters to be learned from O(N2) to O(N) compared with the existing manifold learning algorithm (i.e., automated transform by manifold approximation) (AUTOMAP). This enables DOTA-MRI to be applied to high-resolution MR datasets, which has previously proved difficult to implement in AUTOMAP because of the enormous memory requirements involved. After the initial analytic transform, the manifold learning phase uses a symmetric network architecture comprising three types of layers: front-end convolutional layers, fully connected layers for the 1D global transform, and back-end convolutional layers. The front-end convolutional layers take 1D IFT of the undersampled k-space (i.e., undersampled data in the intermediate domain or in the ky-x domain) as input and performs data-domain restoration. The following fully connected layers learn the 1D global transform between the ky-x domain and the image domain (i.e., the y-x domain). Finally, the back-end convolutional layers reconstruct the final image by denoising in the image domain. DOTA-MRI exhibited superior performance over nine other existing algorithms, including state-of-the-art deep learning-based algorithms. The generality of the algorithm was demonstrated by experiments conducted under various sampling ratios, datasets, and noise levels.


The docent system: an alternate approach to medical education.
There are many applications of the docent system for schools in which students are older and engaging in more conventional educational approaches. There are advantages in bringing students from different classes together over a prolonged period of time, starting with their entrance into the program. Advisors in docent roles can contribute much to such groups. Pairing of more-advanced with less-advanced students, at least informally, may offer some of the advantages described by students at UMKC in their partnerships. Women students may find it much easier to establish helpful relationships with male and female peers and teachers in organized group settings. Faculty may come to experience the advantages for themselves of close personal interaction with students. Better relationships between male and female faculty members can lead to more successful recruitment of excellent female faculty members, which is important with the increased number of women medical students. The concept offers a personalized approach to undergraduate medical education that is worthy of continued study and evaluation.


Structural basis of activity and allosteric control of diguanylate cyclase.
Recent discoveries suggest that a novel second messenger, bis-(3'-->5')-cyclic di-GMP (c-diGMP), is extensively used by bacteria to control multicellular behavior. Condensation of two GTP to the dinucleotide is catalyzed by the widely distributed diguanylate cyclase (DGC or GGDEF) domain that occurs in various combinations with sensory and/or regulatory modules. The crystal structure of the unorthodox response regulator PleD from Caulobacter crescentus, which consists of two CheY-like receiver domains and a DGC domain, has been solved in complex with the product c-diGMP. PleD forms a dimer with the CheY-like domains (the stem) mediating weak monomer-monomer interactions. The fold of the DGC domain is similar to adenylate cyclase, but the nucleotide-binding mode is substantially different. The guanine base is H-bonded to Asn-335 and Asp-344, whereas the ribosyl and alpha-phosphate moieties extend over the beta2-beta3-hairpin that carries the GGEEF signature motif. In the crystal, c-diGMP molecules are crosslinking active sites of adjacent dimers. It is inferred that, in solution, the two DGC domains of a dimer align in a two-fold symmetric way to catalyze c-diGMP synthesis. Two mutually intercalated c-diGMP molecules are found tightly bound at the stem-DGC interface. This allosteric site explains the observed noncompetitive product inhibition. We propose that product inhibition is due to domain immobilization and sets an upper limit for the concentration of this second messenger in the cell.


Homogeneous and high-density gold unit implanted optical labels for robust and sensitive point-of-care drug detection.
Controllable integration of gold building blocks into mesoscopic architecture produces improved optical signals with preferable stability for biological sensing. Here, we developed novel optical labels with homogeneous and high-density implanted hydrophobic gold nanoparticles (AuNPs) throughout three-dimensional silica scaffolds. The dendritic silica supports with an extra-large pore size and highly accessible central-radial channels were employed as metal-affinity templates, for anchoring with AuNPs directly from the organic phase. The nano-assemblies exhibited a high unit loading capacity while maintaining the intrinsic optical characteristics of AuNPs. After phase transfer by the alkylsilane intermediate layer and exterior silica shell encapsulation, the nanocomposites revealed an amplified plasmonic absorption signal, excellent colloidal/optical stability and convenient surface functionalization. By integrating the silica labels into the lateral flow immunoassay strip for signal enhancement, the sensitive point-of-care detection of methamphetamine in urine was established. The limit of detection achieved 0.026 ng mL-1, with a detection range from 0.023 to 375 ng mL-1 in a 10 min assay, allows both visual and on-site quantitative analysis. Encouragingly, the potential interfering drugs in the sample matrix showed a negligible influence on the results, validating the superior specificity of the current immunoassay. The newly developed gold-implanted optical labels show prospects for point-of-care testing in a complex biological matrix with the desirable stability and signal amplification.


Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium.
Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium we found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. Part, but not all, of the lower potency of submucosal adenosine resulted from submucosal uptake and metabolism of the drug. The observation that mucosal 8-phenyltheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.


Ketoconazole treatment of chronic mucocutaneous candidiasis.
Five patients received ketoconazole treatment of chronic mucocutaneous candidiasis. One also had disseminated histoplasmosis and cryptococcosis. Ketoconazole was well absorbed after an oral dose of 200 mg and produced detectable antifungal blood levels for more than eight hours after each dose. Thrush cleared in less than two weeks in all patients. Cutaneous lesions cleared slowly during several months of treatment. A patient with polymycotic infection had a rapid clearing of candidiasis, but her histoplasmosis did not respond to three weeks of treatment. Adverse drug effects were minimal. Ketoconazole is a promising new agent for treatment of chronic mucocutaneous candidiasis.


Factors limiting device efficiency in organic photovoltaics.
The power conversion efficiency of the most efficient organic photovoltaic (OPV) cells has recently increased to over 10%. To enable further increases, the factors limiting the device efficiency in OPV must be identified. In this review, the operational mechanism of OPV cells is explained and the detailed balance limit to photovoltaic energy conversion, as developed by Shockley and Queisser, is outlined. The various approaches that have been developed to estimate the maximum practically achievable efficiency in OPV are then discussed, based on empirical knowledge of organic semiconductor materials. Subsequently, approaches made to adapt the detailed balance theory to incorporate some of the fundamentally different processes in organic solar cells that originate from using a combination of two complementary, donor and acceptor, organic semiconductors using thermodynamic and kinetic approaches are described. The more empirical formulations to the efficiency limits provide estimates of 10-12%, but the more fundamental descriptions suggest limits of 20-24% to be reachable in single junctions, similar to the highest efficiencies obtained for crystalline silicon p-n junction solar cells. Closing this gap sets the stage for future materials research and development of OPV.


Identification of cytomegalovirus-specific cytotoxic T lymphocytes in vitro is greatly enhanced by the use of recombinant virus lacking the US2 to US11 region or modified vaccinia virus Ankara expressing individual viral genes.
Cytomegalovirus (CMV) elicits a potent T-cell response in humans that appears to protect the host from virus-associated disease. Despite facing strong host defense mechanisms, CMV remains as a lifelong infection that may reactivate and cause life-threatening disease in immunocompromised individuals. This persistence is probably assisted by expression of immune subversion proteins of the virus encoded by genes belonging to the US gene family. These proteins modulate major histocompatibility complex expression in infected cells and bias in vitro experiments toward the detection of only certain specificities. We have combined the use of recombinant CMV, lacking the US2 to US11 region genes, and cytoplasmic gamma interferon staining to define a more accurate assessment of CMV-specific responses in vivo. Recombinant CMV stimulation reveals a CD8 response much larger than that of parental virus in all donors tested. In some cases, this represented up to 10-fold increases in the number of cells detected. Responses were directed mainly against pp65, IE-1, and pp50 in the majority of donors. In addition, previously unreported IE-2-specific T-cell responses could be detected in a minority of cases. Furthermore, we observed a less marked increase in the response to mutant CMV by CD4 T cells in some donors. This suggests that a much broader T-cell response to CMV exists in vivo than is revealed by restimulation with wild-type virus and adds to the evidence that the efficacy of immune evasion strategies may not be as absolute as previously believed.


Antigenic variants in Bordetella pertussis strains isolated from vaccinated and unvaccinated children.
Bordetella pertussis shows polymorphism in two proteins, pertactin (Prn) and the pertussis toxin (PT) S1 subunit, which are important for immunity. A previous study has shown antigenic shifts in these proteins in the Dutch B. pertussis population, and it was suggested that these shifts were driven by vaccination. The recent Italian clinical trial provided the opportunity to compare the frequencies of Prn and PT S1 subunit variants in strains isolated from unvaccinated children, and from children vaccinated with two acellular and one whole-cell pertussis vaccine. Four Prn variants (Prn1, Prn2, Prn3 and Prn5) were found in the 129 strains analysed. Prn1, Prn2 and Prn3 have been described previously, whereas Prn5 is a novel variant. Prn1, Prn2, Prn3 and Prn5 were found in, respectively, 6, 41, 51 and 2% of the strains. The B. pertussis strains used to produce the vaccines administered in the clinical trial were found to produce Prn1, or a type which differed from Prn1 in one amino acid. The frequency of the Prn1 variant was found to be lowest in the strains isolated from vaccinated groups, suggesting that Prn1 strains are more affected by vaccine-induced immunity than Prn2 and Prn3 strains. Only one PT S1 type (S1A) was observed in the examined strains, which was distinct from the types produced by the vaccine strains (S1B and S1D). The S1A type also predominates in the Dutch B. pertussis population. The genetic relationship among B. pertussis strains analysed by IS1002-based DNA fingerprinting revealed that three fingerprint types predominate, representing more than 70% of the strains. Prn2 strains showed a greater variety of fingerprint types compared to Prn3, suggesting that Prn3 has emerged more recently. The results are discussed in the light of vaccine-driven evolution.


Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness.
BACKGROUNDRBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.METHODSThis is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.RESULTSBlood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours.CONCLUSIONDonor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.FUNDINGFunding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).


The views of parents concerning the planning of services for rehabilitation of families of children with congenital cardiac disease.
Although much previous research has focused on the medical aspects of congenital cardiac disease, there is a growing body of research which suggests that families may need help and support with the wider issues associated with the medical condition. We have previously ascertained from young people with congenital cardiac disease their views on this subject. The purpose of this study was to obtain the views of their parents about the need for, and shape of, services for rehabilitation. This was a qualitative study using semi-structured interviews. We interviewed 17 parents in their own home. Interviews were tape-recorded and transcribed. Parents would welcome more help and support from health professionals to enable them to manage more effectively the condition with their children. Particular areas of concern relate to the information they receive about the condition; communication between themselves and health professionals; establishing safe levels of activity; and managing the condition at school. This is a small study of the experiences and views of parents, which provides some important information on ways in which health professionals could address the current lack of services for rehabilitation.


Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury.
Fetal development and growth occur in a sterile amniotic cavity while first exposure to microorganisms happens at birth. However, at least 25% of all preterm births, the leading cause of perinatal morbidity and mortality worldwide, occur in mothers with microbial invasion of the amniotic cavity. Microbial attack of the fetus takes place in approximately 10% of pregnancies with intra-amniotic infection, and the human fetus is capable of deploying an inflammatory response (cellular and humoral) in the mid-trimester of pregnancy. The onset of premature labor in the context of infection is mediated by pro-inflammatory cytokines, such as interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha), as these cytokines are produced by intrauterine tissues in response to microbial products, can stimulate prostaglandin production, and induce labor in animals. Moreover, knockout experiments suggest that infection is less likely to lead to premature labor when the IL-1 and TNF signaling pathways are disrupted. A fetal inflammatory systemic response occurs in a fraction of fetuses exposed to microorganisms in utero, and is associated with the impending onset of labor as well as multisystem organ involvement. Neonates born with funisitis, the histologic marker of such inflammation, are at increased risk for neurologic handicap and cerebral palsy. Evidence has begun to accumulate that gene-environment interactions determine the likelihood of preterm labor and delivery and, probably, the risk of fetal injury. Fetal inflammation has emerged as a major mechanism of disease responsible for complications in the perinatal period (in utero and in the first 28 days of life), as well as in infancy. Moreover, reprogramming of the fetal immune response may predispose to diseases in adulthood.


Correction of anemia and iron deficiency in vegetarians by administration of ascorbic acid.
Twenty-eight strict vegetarians were given 500 mg ascorbic acid twice daily after lunch and dinner for two months. Hemoglobin and certain iron status parameters were measured before and after the treatment. Ascorbate treatment increased mean hemoglobin by 8%, serum iron by 17% and transferrin saturation by 23% and decreased total iron binding capacity by 7%. All these changes were statistically significant. The rise in serum ferritin was 12%. The serum protein or copper level did not indicate their dietary deficiency, while initial serum ascorbate level were low which rose by 60% on therapy. It is concluded that ascorbate supplementation is a better method of improving hematologic and iron status than iron salt administration.


Combined radiological and surgical treatment of arteriovenous malformations of the head and neck.
Arteriovenous malformations (AVMs) are high-flow lesions. More than 50% of all AVMs are located in the head and neck region. They represent a therapeutic challenge because of their hemodynamic characteristics and their modality of growth. AVMs have a tendency to recur and often require radical resection, making surgical ablation and reconstruction difficult. AVMs require angiography not only for diagnostic purposes but as an initial therapeutic step in the form of embolization. Surgical ablation, which follows a few days after embolization, is facilitated by the reduction in vascularity and shrinkage of the lesion, both of which are afforded by the embolization. These benefits allow for less blood loss at the time of ablation, and less extensive resection. The authors report their experience with 16 patients with extracranial AVMs of the head and neck examined over the last decade.


d-Glycero-β-d-Manno-Heptose 1-Phosphate and d-Glycero-β-d-Manno-Heptose 1,7-Biphosphate Are Both Innate Immune Agonists.
d-Glycero-β-d-manno-heptose 1,7-biphosphate (β-HBP) is a novel microbial-associated molecular pattern that triggers inflammation and thus has the potential to act as an immune modulator in many therapeutic contexts. To better understand the structure-activity relationship of this molecule, we chemically synthesized analogs of β-HBP and tested their ability to induce canonical TIFA-dependent inflammation in human embryonic kidney cells (HEK 293T) and colonic epithelial cells (HCT 116). Of the analogs tested, only d-glycero-β-d-manno-heptose 1-phosphate (β-HMP) induced TIFA-dependent NF-κB activation and cytokine production in a manner similar to β-HBP. This finding expands the spectrum of metabolites from the Gram-negative ADP-heptose biosynthesis pathway that can function as innate immune agonists and provides a more readily available agonist of the TIFA-dependent inflammatory pathway that can be easily produced by synthetic methods.


Association of vitamin K deficiency with bone metabolism and clinical disease activity in inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a chronic inflammatory process in the digestive tract and patients with IBD develop osteopenia. Although vitamins K and D are important for maintaining bone health and inhibiting inflammation, their roles in patients with IBD are not clear. We investigated the roles of vitamins K and D in the bone health and inflammation in patients with IBD. Bone mineral density (BMD) of patients with IBD (Crohn's disease [CD], n = 47, and ulcerative colitis [UC], n = 40) was measured with dual-energy X-ray absorptiometry. Vitamin K and D levels of patients with IBD and healthy volunteers (n = 41) were evaluated by measuring serum undercarboxylated osteocalcin and 1,25 dihydroxyvitamin D, respectively. Clinical activity index was evaluated in patients with CD and UC. BMD was low in patients with CD and UC. Serum undercarboxylated osteocalcin levels were significantly higher in patients with CD, but not with UC, compared with healthy subjects, indicating that bone vitamin K is insufficient in patients with CD. The levels of undercarboxylated osteocalcin were significantly correlated with the clinical activity index of CD, although they were not correlated with BMD. The levels of 1,25 dihydroxyvitamin D were significantly lower in patients with CD and UC than in healthy subjects. The levels of 1,25 dihydroxyvitamin D were inversely correlated with BMD in patients with UC and were not correlated with the clinical activity index of CD. Vitamins K and D are insufficient in patients with IBD. Insufficiency of vitamin K is suggested to be associated with inflammatory processes of CD.


Anakinra and canakinumab for patients with R92Q-associated autoinflammatory syndrome: a multicenter observational study from the AIDA Network.
This study aims at describing the therapeutic outcome of patients carrying the R92Q variant in the TNFRSF1A gene treated with anakinra (ANA) or canakinumab (CAN) and identifying any factors predictive of complete response to IL-1 inhibition. Clinical data of patients treated with ANA or CAN for recurrent inflammatory attacks due to the presence of the R92Q variant were retrospectively collected and analysed. Data about 20 treatment courses with IL-1 inhibitors (16 with ANA and 4 with CAN) from 19 patients were collected. Mean age at disease onset was 20.2 ± 14.8 years. In 5 cases (26%) the R92Q variant was found in a family member affected by recurrent fever. The therapeutic response was complete in 13(68%) and partial in 2 patients (11%); treatment failure was observed in 4 cases (21%). Median AIDAI decreased from 10 (interquartile range [IQR] = 28) to 0 (IQR = 1) at the 12-month follow-up visit (p < 0.001). Mean ESR and median CRP dropped respectively from 40.8 ± 24.8 to 9.1 ± 4.5 mm/h (p < 0.001) and from 3.0 (IQR = 1.9) to 0.3 (IQR = 0.3) mg/dl (p < 0.001) after 12 months of treatment. A steroid-sparing effect was observed from the third month of treatment (p < 0.01). Thirteen patients (65%) were still on treatment at the last follow-up visit (median duration of treatment 17 (IQR = 38) months). The presence of R92Q mutation in a symptomatic relative (p = 0.022), the relapsing remitting disease course (p < 0.001) and the presence of migratory erythematous skin rashes during fever attacks (p = 0.005) were associated with complete efficacy of IL-1 inhibitors. R92Q patients showed a favourable response to ANA and CAN, particularly when the mutation segregated in a family member and when a relapsing-remitting disease course or TNF-α receptor-associated periodic syndrome (TRAPS) typical skin rash were observed. In the subgroup of patients not taking advantage of IL-1 blockage different molecular mechanisms underlying the autoinflammatory picture are likely to exist.


Prevention of acute otitis media using currently available vaccines.
Acute otitis media (AOM) is common in infants and children. Although approximately two-thirds of cases are due to bacteria, almost all of the episodes are preceded by upper respiratory viral infection. Several viruses, among which respiratory syncytial virus is the most common, are involved in the determination of AOM. However, a significant number of AOM cases are associated with influenza infection, and influenza viruses are among the most frequently found respiratory viruses in the middle ear fluid during an acute episode of AOM. Consequently, influenza vaccination may have a favorable impact on the incidence and course of AOM. Moreover, as Streptococcus pneumoniae is one of the leading AOM bacterial pathogens and it is well known that influenza virus infection predisposes to pneumococcal infection, there is a further reason to suggest the use of influenza vaccine to reduce the risk of AOM. On the other hand, the administration of pneumococcal conjugate vaccine is considered per se a possible means of reducing the incidence of the disease. However, although a number of studies have measured the impact of both vaccines on AOM, it is still not known whether (and to what extent) they are really effective, nor what impact the more recently licensed vaccines may have. The aim of this review is to examine the clinical impact of vaccinations on AOM.


Referral of patients with depression to mental health care by Dutch general practitioners: an observational study.
Depression is a common illness, often treated in primary care. Guidelines provide recommendations for referral to mental health care. Several studies investigated determinants of referral, none investigated guideline criteria as possible determinants.We wanted to evaluate general practitioner's referral of depressed patients to mental health care and to what extent this is in agreement with (Dutch) guideline recommendations. We used data of primary care respondents from the Netherlands Study of Depression and Anxiety with major depressive disorder in the past year (n = 478). We excluded respondents with missing data (n = 134). Referral data was collected from electronic patient files between 1 year before and after baseline and self report at baseline and 1-year follow-up. Logistic regression was used to describe association between guideline referral criteria (e.g. perceived need for psychotherapy, suicide risk, severe/chronic depression, antidepressant therapy failure) and referral. A high 58% of depressed patients were referred. Younger patients, those with suicidal tendency, chronic depression or perceived need for psychotherapy were referred more often. Patients who had used ≥2 antidepressants or with chronic depression were more often referred to secondary care. Referred respondents met on average more guideline criteria for referral. However, only 8-11% of variance was explained. The majority of depressed patients were referred to mental health care. General practitioners take guideline criteria into account in decision making for referral of depressed patients to mental health care. However, other factors play a part, considering the small percentage of variance explained. Further research is necessary to investigate this.


Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.
Proteoglycans (PGs), a family of glycosaminoglycan (GAG)-protein glycoconjugates, contribute to animal physiology through interactions between their glycan chains and growth factors, chemokines and adhesion molecules. However, it remains unclear how GAG structures are changed during the aging process. Here, we found that polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin. In cultured cell lines, the EXT1 and EXT2 enzymes, initiating HS biosynthesis, were stimulated at the translational level by polyamines. Interestingly, the initiation codon recognition by 43S preinitiation complex during EXT2 translation is suppressed by let-7b, a member of the let-7 microRNA family, through binding at the N-terminal amino acid coding sequence in EXT2 mRNA. Let-7b-mediated suppression of initiation codon depends on the length of 5'-UTR of EXT2 mRNA and its suppression is inhibited in the presence of polyamines. These findings provide new insights into the HS biosynthesis related to miRNA and polyamines.


cAMP-dependent reduction in membrane fluxes during relaxation of arterial smooth muscle.
Forskolin, an activator of adenylate cyclase, inhibited contractures induced in rat aorta by norepinephrine (NE) and angiotensin II and by KCl depolarization. The concentration of forskolin required to inhibit NE-induced contractures was significantly lower than required to inhibit KCl-induced contractures (IC50 0.18 +/- 0.01 vs. 2.2 +/- 0.2 microM). Forskolin effectively relaxed NE-induced contractures when active Na+-K+ transport was inhibited. Stimulation of 42K and 36Cl effluxes by NE was inhibited by low concentrations of forskolin. The IC50 for forskolin inhibition of 42K efflux, 0.17 +/- 0.02 M, was similar to that for relaxation of NE contraction. The time course for forskolin-induced increases in adenosine 3',5'-cyclic monophosphate (cAMP) was consistent with that for forskolin-mediated relaxation and its maintenance. Fifty percent inhibition of both NE-induced contractures and NE-stimulated 42K effluxes occurred at levels of cAMP that were 1.4 times basal, and 90% inhibition of both processes was associated with a two to threefold increase in cAMP content. In sharp contrast, the level of tissue cAMP associated with inhibition of KCl contractures was 6-10 times higher than that associated with inhibition of NE-induced contractures. We postulate that cAMP-dependent regulation of membrane fluxes stimulated by receptor occupancy represents a primary mechanism for relaxation of a NE contracture, whereas the processes that regulate depolarization-dependent channels and the phosphorylation of myosin light chain kinase occur at much higher cAMP content and apparently function in a secondary capacity.


The correlation of the spraying volume with herbicide adherence and herbicide penetration in glyphosate treatments.
The relationship between the spraying volume and glyphosate effectiveness has been widely studied over the years. Likewise, the effect of different adjuvants on glyphosate leaf adherence/penetration is currently well understood. However, not much is known about the way spraying volumes may influence these two herbicide properties or, in other words, which factor (adherence or penetration) is the limiting factor when spraying at low or high volumes of treatment. Using grass-weed Lolium rigidum and broad-leaved weed Portulaca oleracea as experimental systems, the effect of low (200 L ha(-1)) and high (800 L ha(-1)) spraying volumes and six commercial adjuvants (poly-l-p-menthene, a mixture of methyl oleate and palmitate, alkylglycol ester, dodecylbenzene ammonium sulphonate, and two paraffinic oils) plus ammonium sulfate on the effectiveness of five commercial glyphosate formulations has been studied under laboratory controlled conditions. Dose-response assays showed significant differences between low and high spraying volume treatments as expected, the former being much more effective than the latter. However, and in all commercial formulations and weed species tested, the best results at low spraying volumes were always obtained when formulating glyphosate with oils or their derivatives, with a minimal improvement observed in glyphosate/surfactant mixtures. On the contrary, both the use of ionic or non-ionic surfactants as glyphosate adjuvants gave the best results at high spraying volumes, with only a marginal success observed on paraffinic oils and fatty acidesters. Data point out glyphosate absorption as being a two-step process made up of adherence first and then penetration, both events being essential for glyphosate effectiveness. Under these terms, high performance glyphosate-rich low spraying volumes succeed by themselves in soaking leaf surfaces, penetration therefore being the main and only limiting factor, while low performance glyphosate-poor high spraying volumes fail to either soak or penetrate leaf cuticles. The use of penetrative agents such as oils is therefore advised as a single method to increase glyphosate effectiveness at low spraying volumes, whereas glyphosate treatments at high spraying volumes are better improved by using surfactant agents or surfactant + oil mixtures.


Methods of assigning accurate values to reference serum. Part 1. The use of reference laboratories and consensus values, with an evaluation of a procedure for transferring values from one reference serum to another.
A method is described for transferring the accuracy of values obtained by reference laboratories from one serum, which is used as a calibration standard, to another, which is treated as the unknown test sample. Six batches of lyophilised horse serum, of closely similar composition, were analysed by 10 European reference laboratories during 1978-1982, and used to obtain transfer values for one masterlot of a similar serum. No evidence was found that the transfer process introduced any inaccuracy. A comparison has been made, for bilirubin, creatinine, iron, phosphate, total protein and urea, between transferred values, the results obtained by direct analysis of the masterlot by reference laboratories, and consensus values found in two independent external quality assessment schemes. The transfer technique enables an evaluation to be made of these different procedures for assigning values to reference serum, and may reveal methodological differences, such as those described for iron and creatinine.


Unusual side effects due to warfarin.
Two cases demonstrating unusual side effects of warfarin are described. The first case illustrates the 'purple toes' syndrome, which occurred as a complication following the use of warfarin for the treatment of atrial fibrillation and stroke. The second case is an example of warfarin-induced vasculitis in a patient with a mechanical valve prosthesis. He was unable to tolerate warfarin but was successfully managed with nicoumalone, a related compound. These complications are rare but potentially dangerous effects of a commonly used agent, warfarin.


Vitamin D3--resistant fibroblasts have immunoassayable 1,25-dihydroxyvitamin D3 receptors.
Cultured fibroblasts obtained from patients with tissue resistance to 1,25-dihydroxyvitamin D3 (vitamin D3--dependent rickets, type II) contain normal, low, or undetectable concentrations of this hormone's receptor protein as measured by a ligand-binding assay. Extracts from these cells were evaluated for receptors by immunoassay with a recently developed monoclonal antibody to the chick receptor. The results show that a protein sedimenting at 3.7S and recognizable by the antibody exists in comparable concentrations in cells from both normal and resistant patients, irrespective of the hormone-binding abnormalities of the cells. This implies that deficiencies in hormone binding associated with inherited tissue resistance to 1,25-dihydroxyvitamin D3 probably arise from structural variations in the receptor molecule and not from defective receptor synthesis.


Prognosis factors in cancer of the vulva.
A series of factors and its possible influence on the prognosis of cancer of the vulva are analyzed. In the present study 71 patients were studied. We have been able to establish that the main prognosis factor of cancer of the vulva is, beyond doubt, the presence of lymph node metastasis, since in absence of lymph node affection due to the cancer, survival was 100%, after five years, in those patients having positive lymph nodes, survival was 92.5% after the first year, 82.5% after three years and 70% after five years.


Relationship Between Different Resistance Mechanisms and Virulence in Acinetobacter baumannii.
Aim: This study analyzed the virulence of several Acinetobacter baumannii strains expressing different resistance mechanisms using the Caenorhabditis elegans infection model. Results: Strains susceptible/resistant to carbapenems (presenting class D (OXA-23, OXA-24), class B metallo-β-lactamase (MBL) (NDM-1), penicillin binding protein (PBP) altered and decreased expression of Omp 33-36 kDa) and isogenic A. baumannii strains susceptible/resistant to colistin (presenting loss of lipopolysaccharide (LPS) and pmrA mutations) were included to evaluate the virulence using the C. elegans infection model. The nematode killing assay, bacterial ingestion in worms, and bacterial lawn avoidance assay were performed with the Fer-15 mutant line. A. baumannii strains generally presented low virulence, showing no difference between carbapenem-resistant strains (expressing class D, MBLs, or altered PBP) and their isogenic susceptible strains. In contrast, the absence of the Omp 33-36 kDa protein in the knockout was associated with a decrease of virulence, and a significant difference was observed between colistin-resistant mutants and their susceptible counterpart when the mechanism of resistance was associated with the loss of LPS but not with its modification. Conclusions: Resistance to carbapenems in A. baumannii associated with the production of OXA-type or NDM-type enzymes does not seem to affect their virulence in the C. elegans infection model. In contrast, the presence of Omp 33-36 kDa, and high level resistance to colistin related with the loss of LPS, might contribute with the virulence profile in A. baumannii.


Huffmanela mexicana n. sp. (Nematoda: Trichosomoididae) from the marine fish Sphoeroides annulatus in Mexico.
A new species of trichosomoidid nematodes, Huffmanela mexicana n. sp., is established on the basis of its egg morphology and biological characters. The dark-shelled, embryonated eggs of this histozoic parasite occur in masses in the inner layer of the swimbladder wall of the bullseye puffer fish Sphoeroides annulatus Jenyns, 1843 (Tetraodontidae, Tetraodontiformes) off the Pacific coast of Mexico (Sinaloa State) and are characterized mainly by their shape and size (63-69 x 30-33 microm), an aspinose surface, relatively small polar plugs, and their thick egg wall (4-5 microm). A key to Huffmanela species based on egg morphology is presented.


Bioactive Compounds and Diabetes Mellitus: Prospects and Future Challenges.
Diabetes mellitus is a metabolic condition that influences the endocrine framework. Hyperglycemia and hyperlipidemia are two of the most widely recognized metabolic irregularities in diabetes and two of the most well-known reasons for diabetic intricacies. Diabetes mellitus is a persistent illness brought about by metabolic irregularities in hyperglycemic pancreatic cells. Hyperglycemia can be brought about by an absence of insulin-producing beta cells in the pancreas (Type 1 diabetes mellitus) or inadequate insulin creation that does not work effectively (Type 2 diabetes mellitus). Present diabetes medication directs blood glucose levels in the systemic circulation to the typical levels. Numerous advanced prescription medicines have many negative results that can bring about unexpected severe issues during treatment of the bioactive compound from a different source that is beneficially affected by controlling and adjusting metabolic pathways or cycles. Moreover, a few new bioactive medications disengaged from plants have shown antidiabetic action with more noteworthy adequacy than the oral hypoglycemic agent that specialists have utilized in clinical treatment lately. Since bioactive mixtures are collected from familiar sources, they have a great activity in controlling diabetes mellitus. This study discusses bioactive compounds, their activity in managing diabetes mellitus, and their prospects. Though bioactive compounds have many health-beneficial properties, adequate clinical studies still need to acknowledge that they effectively manage diabetes mellitus.


Calmodulin antagonism and growth-inhibiting activity of triphenylethylene antiestrogens in MCF-7 human breast cancer cells.
The triphenylethylene antiestrogen tamoxifen has been shown previously to inhibit both calmodulin and protein kinase C activities, which are involved in the control of cell proliferation. We have studied the effect of several derivatives of the triphenylethylene antiestrogen family on the inhibition of both calmodulin-dependent cyclic adenosine 3':5'-monophosphate-phosphodiesterase activity and proliferation of breast cancer cells cultured with 0.5 microM estradiol in order to prevent interaction of these drugs with the estrogen receptor. We have observed that hydroxylation of the triphenylethylene molecule significantly decreases its ability to inhibit the calmodulin-dependent phosphodiesterase activity in vitro. Furthermore, the growth-inhibiting activity of several antiestrogens and other calmodulin antagonists [R24571, trifluoperazine, N-(6-aminohexyl)-5-chloronaphthalene-1-sulfonamide, and N-(6-aminohexyl)-1-naphthalenesulfonamide] correlated with their antagonistic effects on calmodulin activity. The level of activity was determined as follows: R24571 greater than tamoxifen = N-demethyltamoxifen = nafoxidine greater than 4-hydroxytamoxifen greater than 3,4-dihydroxytamoxifen = trifluoperazine greater than N-(6-aminohexyl)-5-chloronaphthalene-1-sulfononamide greater than metabolite A greater than N-(6-aminohexyl)-1-naphthalenesulfonamide. On the other hand both protein kinase C-activating and -inhibiting drugs (phorboltetradecanoate-13-acetate and tamoxifen, respectively) have a synergistic inhibitory effect on the growth of MCF-7 cells. Our data suggest that antiestrogen interactions with calmodulin and not protein kinase C may play a role in mediating the drug-induced estrogen-independent inhibition of breast cancer cell growth.


AGRICULTURAL RESEARCH IN CHINA. II.
The rapid expansion of agricultural research in China in recent years is one indication of the wide-spread interest among Chinese leaders in improving the living conditions of the people. The present tendency is to work primarily on problems of an immediate practical importance. With the basic farm crops the immediate end in view is to make China self-sufficient. There is, however, in China a growing appreciation of the value of agricultural research as one means of helping to develop efficiency in agriculture.


Protective effects of Ginkgo Biloba Dropping Pills against liver ischemia/reperfusion injury in mice.
Liver ischemia/reperfusion (I/R) injury is an inevitable pathological phenomenon in various clinical conditions, such as liver transplantation, resection surgery, or shock, which is the major cause of morbidity and mortality after operation. Ginkgo Biloba Dropping Pill (GBDP) is a unique Chinese Ginkgo Biloba leaf extract preparation that exhibits a variety of beneficial biological activities. The aim of this study is to investigate the protective effects of GBDP on the liver I/R injury both in the in vitro and in vivo. Hypoxia/reoxygenation (H/R) experiments were performed in alpha mouse liver 12 (AML-12) cells and primary hepatocytes, which were pretreated with GBDP (60 or 120 µg/mL) followed by incubation in a hypoxia chamber. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining as well as western blot analysis of apoptosis-related proteins was performed to detect the protective effect of GBDP on cell apoptosis induced by H/R injury. C57BL/6 mice were used to establish the liver I/R injury model, and were pretreated with GBDP (100 or 200 mg/kg/day, i.g.) for two weeks. The liver damage was evaluated by detection of plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST), as well as histopathological examinations. Liver inflammation was determined by detecting the secretion of pro-inflammatory cytokines and neutrophil infiltration through enzyme-linked immunosorbent assay (ELISA) and myeloperoxidase (MPO) immunohistochemistry staining. Finally, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick and labeling (TUNEL) staining and western blot analysis of apoptosis-related proteins were used to investigate the anti-apoptotic effect of GBDP in mice. In the in vitro study, GBDP pretreatment improved the cell viability of AML-12 cells in the H/R injury model. Similarly, the same result was found in the primary hepatocytes isolated from C57BL/6 mice. Moreover, GBDP decreased the number of apoptotic cells and reduced the expression of apoptosis-related proteins induced by H/R injury. In the in vivo study, oral administration of GBDP ameliorated liver injury evidenced by a significant decline in the levels of ALT and AST. Furthermore, the result of hematoxylin and eosin (H&E) staining showed that GBDP reduced the size of necrosis area in the liver tissue. In addition, the decreased infiltration of neutrophils and secretion of pro-inflammatory cytokines indicated that GBDP may play an anti-inflammatory effect. More importantly, GBDP reduced TUNEL-positive cells and the expression of apoptosis-related proteins in the liver indicating GBDP has anti-apoptotic effects. Our findings elucidated that GBDP has potential effects for protecting against liver I/R injury characterized by its anti-apoptotic, anti-necrotic, and anti-inflammatory properties, which would promisingly make contributions to the exploration of therapeutic strategies in the liver I/R injury.


A reaction-based near-infrared fluorescent probe that can visualize endogenous selenocysteine in vivo in tumor-bearing mice.
Monitoring the fluctuations of endogenous selenocysteine (Sec) in vivo is of significant interest to understand the physiological roles of Sec and the mechanisms of Sec-relevant diseases. Herein, a new near-infrared fluorescent probe, Fsec-1, has been developed for the determination of endogenous Sec in living cells and in vivo. Fsec-1 exhibits large fluorescence enhancement (136-fold) and a remarkably large Stokes shift (195 nm) when reacted with Sec. With the advantages of high sensitivity (a detection limit of 10 nM), good selectivity and low cytotoxicity, Fsec-1 was able to recognize both exogenous and endogenous Sec in living cells. The probe was also successfully applied in visualizing both exogenous and endogenous Sec in living mice. Notably, endogenously generated Sec in living tumors xenografted in nude mice was selectively detected by our reaction-based NIR probe for the first time. These results indicated that our new probe could serve as an efficient tool in monitoring endogenous Sec in vivo and exploring the anticancer mechanism of selenium.


Smokefree legislation effects on respiratory and sensory disorders: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis is to synthesize the available evidence in scientific papers of smokefree legislation effects on respiratory diseases and sensory and respiratory symptoms (cough, phlegm, red eyes, runny nose) among all populations. Systematic review and meta-analysis were carried out. A search between January 1995 and February 2015 was performed in PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and Google Scholar databases. Inclusion criteria were: 1) original scientific studies about smokefree legislation, 2) Data before and after legislation were collected, and 3) Impact on respiratory and sensory outcomes were assessed. Paired reviewers independently carried out the screening of titles and abstracts, data extraction from full-text articles, and methodological quality assessment. A total number of 1606 papers were identified. 50 papers were selected, 26 were related to symptoms (23 concerned workers). Most outcomes presented significant decreases in the percentage of people suffering from them, especially in locations with comprehensive measures and during the immediate post-ban period (within the first six months). Four (50%) of the papers concerning pulmonary function reported some significant improvement in expiratory parameters. Significant decreases were described in 13 of the 17 papers evaluating asthma hospital admissions, and there were fewer significant reductions in chronic obstructive pulmonary disease admissions (range 1-36%) than for asthma (5-31%). Six studies regarding different respiratory diseases showed discrepant results, and four papers about mortality reported significant declines in subgroups. Low bias risk was present in 23 (46%) of the studies. Smokefree legislation appears to improve respiratory and sensory symptoms at short term in workers (the overall effect being greater in comprehensive smokefree legislation in sensory symptoms) and, to a lesser degree, rates of hospitalization for asthma.


Towards clinical grating-interferometry mammography.
Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose. We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device. Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study. • Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.


Rectal Delivery of a DNAzyme That Specifically Blocks the Transcription Factor GATA3 and Reduces Colitis in Mice.
GATA3 is a transcription factor that regulates T-cell production of cytokines. We investigated the role of GATA3 in development of colitis in mice. We performed quantitative polymerase chain reaction and immunofluorescence analyses of colon tissues from patients with Crohn's disease (n = 61) or ulcerative colitis (UC, n = 74) or from patients without inflammatory bowel diseases (n = 22), to measure levels of GATA3. Colitis was induced by administration of oxazolone or 2,4,6-trinitrobenzenesulfonic acid to control mice, mice with T-cell-specific deletion of GATA3, and mice with deletion of tumor necrosis factor receptor (TNFR) 1 and TNFR2 (TNFR double knockouts); some mice were given a GATA3-specific DNAzyme (hgd40) or a control DNAzyme via intrarectal administration, or systemic injections of an antibody to TNF before or during sensitization and challenge phase of colitis induction. Colon tissues were collected and immunofluorescence and histochemical analyses were performed. Lamina propria mononuclear cells and T cells were isolated and analyzed by flow cytometry or cytokine assays. Colonic distribution of labeled DNAzyme and inflammation were monitored by in vivo imaging (endoscopy) of mice. Levels of GATA3 messenger RNA were higher in colon tissues from patients with UC, but not ileal Crohn's disease, than control tissues; levels of GATA3 correlated with levels of inflammatory cytokines (interleukin [IL] 9, IL17A, IL6, IL5, IL4, IL13, and TNF). We observed increased expression of GATA3 by lamina propria T cells from mice with colitis compared with controls. Mice with T-cell-specific deletion of GATA3 did not develop colitis and their colonic tissues did not produce inflammatory cytokines (IL6, IL9, or IL13). The DNAzyme hgd40 inhibited expression of GATA3 messenger RNA by unstimulated and stimulated T cells, and distributed throughout the inflamed colons of mice with colitis. Colon tissues from mice given hgd40 had reduced expression of GATA3 messenger RNA, compared with mice given a control DNAzyme. Mice given hgd40 did not develop colitis after administration of oxazolone or 2,4,6-trinitrobenzenesulfonic acid; lamina propria cells from these mice expressed lower levels of IL6, IL9, and IL13 than cells from mice given the control DNAzyme. Mini-endoscopic images revealed that hgd40 and anti-TNF reduced colon inflammation over 3 days; hgd40 reduced colitis in TNFR double-knockout mice. Levels of GATA3 are increased in patients with UC and correlate with production of inflammatory cytokines in mice and humans. A DNAzyme that prevents expression of GATA3 reduces colitis in mice, independently of TNF, and reduces levels of cytokines in the colon. This DNAzyme might be developed for treatment of patients with UC.


Update on the cytologic and molecular features of medullary thyroid carcinoma.
Medullary thyroid carcinoma (MTC) accounts for only 5% to 10% of all thyroid carcinomas, but it is the most aggressive form of well-differentiated thyroid carcinoma, being responsible for 8% to 15% of all thyroid cancer-related deaths. MTC is frequently diagnosed at a locally advanced or metastatic stage, and 10-year survival rates in these cases are <20%. Fine-needle aspiration biopsy of the thyroid gland is an accurate method to diagnose MTC, having a high sensitivity and specificity. The cytologic features of MTC are characteristic and the cytologic diagnosis of classic MTC is often straightforward, especially when combined with immunocytochemistry. However, because of its morphologic heterogeneity and overlap with other tumors, the differential diagnosis of MTC on cytology and on histology is broad with several potential pitfalls. Significant advances have been made over the last decade in understanding MTC. This concerns mainly the early detection of MTC, especially in familial forms (eg, multiple endocrine neoplasia type 2), and the identification of key molecular pathways and alterations which now offer promising targets for specific therapies in progressive MTC cases. Genetic testing (eg, RET mutation) has allowed for early detection in asymptomatic carriers and high-risk patients, with prophylactic thyroidectomy often being curative. Targeted therapies with multityrosine-kinase inhibitors (eg, vandetanib or cabozantinib) have emerged as promising new treatments for recurrent or metastatic MTC. In this review article, we discuss the cytologic features of MTC and its variants, its differential diagnosis, the role of ancillary studies, and the salient molecular features of MTC.


Anatomy of the posterior iliac crest as a reference to sacral bar insertion.
There are no detailed anatomic studies focusing on the posterior iliac crest although it frequently is used for posterior stabilization of unstable pelvic fractures. Anatomic dissections were done to evaluate the size of the extraarticular region of the posterior iliac crest and its relationship to the lumbosacral lamina and to show on cadavers the level of sacral bar placement that offers safe and solid fixation. Sixty cadavers were dissected bilaterally. Fifty-one were male and nine were female. The distance between the posterior wall of the sacral canal and the tip of the iliac crest was measured at various levels between the level of the upper border of L5 lamina to the level of the posterosuperior iliac spine. In all the dissections the greatest distances were at the level of the L5-S1 junction, which consequently is the safest level for good bony purchase. The entire length of the posterior iliac crest from the level of the upper border of L5 lamina to the posterosuperior iliac spine was shown to be appropriate for safe and solid bar fixation because all of the distance measurements were greater than 13 mm, which is the smallest safe distance. Below the posterosuperior iliac spine level, insertion of the sacral bars was dangerous because the average measured distance was only 10.38 mm.


Potentiation of slow action potentials with theophylline or "micro" adenosine deaminase.
The effects of endogenous adenosine on rat atrial and ventricular slow action potentials (AP) were studied using theophylline, an adenosine receptor antagonist, or "micro" adenosine deaminase (mADA), small polypeptides having adenosine deaminase activity. Exogenous adenosine (10(-6) M) depressed slow APs at low and high isoproterenol concentrations and shifted the isoproterenol dose-response curve to the right in the atrium. In the ventricle, exogenous adenosine inhibited slow APs at low isoproterenol doses and only shifted the bottom of the dose-response relationship to the right. mADA (0.84 U) or theophylline (5 X 10(-5) M) potentiated the response to threshold concentrations of isoproterenol and caused a parallel shift of the curve to the left in the atrium but only shifted the bottom portion of the curve in the ventricle. This potentiation of slow APs in the presence of mADA or theophylline suggests that endogenous adenosine attenuates the response to isoproterenol in cardiac muscle.


Regulation of aromatase gene expression in the adult rat brain.
Brain aromatase plays an important role in the regulation of adult reproductive behavior in male rodents. This report focuses on recent experiments from our laboratory that examined the distribution and regulation of aromatase mRNA in the rat brain. Aromatase mRNA was measured by a highly sensitive ribonuclease protection assay using a 32P-labeled antisense RNA probe that was complimentary to the 5' coding region of rat aromatase mRNA. This probe protects two RNA fragments in rat brain tissue: a 430-nt length fragment and a shorter 300-nt fragment. The presence of the 300-nt RNA fragment is not associated with enzyme activity in the rat brain and appears to represent an alternative brain-specific aromatase transcript whose function, if any, is unknown. In contrast, the 430-nt RNA fragment represents mRNA, which is thought to encode functional aromatase enzyme because its levels are correlated with aromatase activity concentrations in preoptic area, hypothalamus, amygdala, and ovary. Aromatase activity and mRNA levels in the preoptic area and hypothalamus decreased by 7 days after castration and were maintained at intact levels by treatment with testosterone and dihyhdrotestosterone, but not with estradiol. In contrast, neither aromatase activity nor mRNA levels in the amygdala are affected by castration or hormone replacement. In addition, sex differences in the regulation of aromatase mRNA were apparent in both the preoptic area and hypothalamus. These results demonstrate that androgens regulate the transcription or stability of aromatase mRNA in specific brain areas. Moreover, they suggest that gender differences in androgen responsiveness play an important role in regulating gene expression in the adult rat brain.


Genome-scale phylogeny and the detection of systematic biases.
Phylogenetic inference from sequences can be misled by both sampling (stochastic) error and systematic error (nonhistorical signals where reality differs from our simplified models). A recent study of eight yeast species using 106 concatenated genes from complete genomes showed that even small internal edges of a tree received 100% bootstrap support. This effective negation of stochastic error from large data sets is important, but longer sequences exacerbate the potential for biases (systematic error) to be positively misleading. Indeed, when we analyzed the same data set using minimum evolution optimality criteria, an alternative tree received 100% bootstrap support. We identified a compositional bias as responsible for this inconsistency and showed that it is reduced effectively by coding the nucleotides as purines and pyrimidines (RY-coding), reinforcing the original tree. Thus, a comprehensive exploration of potential systematic biases is still required, even though genome-scale data sets greatly reduce sampling error.


Neuregulin-ErbB signaling promotes microglial proliferation and chemotaxis contributing to microgliosis and pain after peripheral nerve injury.
A key component in the response of the nervous system to injury is the proliferation and switch to a "proinflammatory" phenotype by microglia (microgliosis). In situations where the blood-brain barrier is intact, microglial numbers increase via the proliferation and chemotaxis of resident microglia; however, there is limited knowledge regarding the factors mediating this response. After peripheral nerve injury, a dorsal horn microgliosis develops, which directly contributes to the development of neuropathic pain. Neuregulin-1 (NRG-1) is a growth and differentiation factor with a well characterized role in neural and cardiac development. Microglia express the NRG1 receptors erbB2, 3, and 4, and NRG1 signaling via the erbB2 receptor stimulated microglial proliferation, chemotaxis, and survival, as well as interleukin-1beta release in vitro. Intrathecal treatment with NRG1 resulted in microglial proliferation within the dorsal horn, and these cells developed an activated morphology. This microglial response was associated with the development of both mechanical and cold pain-related hypersensitivity. Primary afferents express NRG1, and after spinal nerve ligation (SNL) we observed both an increase in NRG1 within the dorsal horn as well as activation of erbB2 specifically within microglia. Blockade of the erbB2 receptor or sequestration of endogenous NRG after SNL reduced the proliferation, the number of microglia with an activated morphology, and the expression of phospho-P38 by microglia. Furthermore, consequent to such changes, the mechanical pain-related hypersensitivity and cold allodynia were reduced. NRG1-erbB signaling therefore represents a novel pathway regulating the injury response of microglia.


Distribution of small integrin-binding ligand, N-linked glycoproteins (SIBLING) in the condylar cartilage of rat mandible.
The Small Integrin-Binding LIgand, N-linked Glycoprotein (SIBLING) family is one category of non-collagenous proteins closely related to osteogenesis. In this study, the authors systematically evaluated the presence and distribution of four SIBLING family members, dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone sialoprotein (BSP) and osteopontin (OPN), in rat mandibular condylar cartilage using protein chemistry and immunohistochemistry. For protein chemistry, SIBLING proteins in the dissected condylar cartilage were extracted with 4M guanidium-HCl, separated by ion-exchange chromatography, and analyzed by Western immunoblotting. Immunohistochemistry was employed to assess the distribution of these four SIBLING proteins in the condylar cartilage of 2-, 5- and 8-week-old rats. Results from both approaches showed that all four members are expressed in the condylar cartilage. DSPP, unlike that observed in dentin and bone, exists as a full-length form (uncleaved) in the condylar cartilage. The NH(2)-terminal fragment of DMP1 is mainly detected in the matrix of the cartilage while the COOH-terminal fragment is primarily localized in the nuclei of cells in the chondroblastic and hypertrophic layers. The data obtained in this investigation provide clues about the potential roles of these SIBLING proteins in chondrogenesis.


Comparison of the effect of betamethasone versus dexamethasone on the amniotic fluid index in the women at risk of preterm labor.
The aim of this study was to compare the biophysical profile parameters (BPP), especially amniotic fluid index (AFI), before and after administration of corticosteroids (dexamethasone and betamethasone) and these two groups with each other. This double-blind clinical trial study was done on 70 patients for 28-34 weeks women having at least one preterm labor in their previous pregnancy has been submitted in Al Zahra and Shahid Beheshti clinic in 2012-2013. 70 women were randomly allocated in two groups. The first group were received 8 mg each 12 h for 4 doses dexamethasone when the patient at risk of preterm labor admitted in clinic or hospitalized and the second group were received 12 mg betamethasone each 24 h similarly. Nonstress test (NST) and BPP and sonography AFI were done in all cases, and then NST was done in the before and 3 days after intervention. Data were analyzed by SPSS software version 20 using t-test, Chi-square, and Fisher's test. There was no significant difference between the range of AFI before and after the drug intervention (P > 0.05). Two groups had no significant difference in AFI before and after administration of corticosteroids. No significant difference was seen in NST acceleration tests between the two groups before and after corticosteroids administration. Biophysical profile had a significant difference in dexamethasone group respect to that of betamethasone group. Furthermore, the biophysical profile had a significant difference before and after the administration of corticosteroids in two groups. It is noted that AFI had no role in this matter.


Fine tuning cellular recognition: The function of the leucine rich repeat (LRR) trans-membrane protein, LRT, in muscle targeting to tendon cells.
The formation of complex tissues during embryonic development is often accompanied by directed cellular migration towards a target tissue. Specific mutual recognition between the migrating cell and its target tissue leads to the arrest of the cell migratory behavior and subsequent contact formation between the two interacting cell types. Recent studies implicated a novel family of surface proteins containing a trans-membrane domain and single leucine-rich repeat (LRR) domain in inter-cellular recognition and the arrest of cell migration. Here, we describe the involvement of a novel LRR surface protein, LRT, in targeting migrating muscles towards their corresponding tendon cells in the Drosophila embryo. LRT is specifically expressed by the target tendon cells and is essential for arresting the migratory behavior of the muscle cells. Additional studies in Drosophila S2 cultured cells suggest that LRT forms a protein complex with the Roundabout (Robo) receptor, essential for guiding muscles towards their tendon partners. Genetic analysis supports a model in which LRT performs its activity non-autonomously through its interaction with the Robo receptors expressed on the muscle surfaces. These results suggest a novel mechanism of intercellular recognition through interactions between LRR family members and Robo receptors.


Recognition of distorted patterns using the viterbi algorithm.
In this paper a new recognition system of distorted patterns is presented, where the Viterbi algorithm and a modified trellis incorporating a pertinent statistics of distorted patterns are used. The system works in a manner quite similar to our own human decision process. The trellis is so constructed that it can eliminate all the irrelevant pattern classes at the outset and leave only the most probable for its fimal decision, yielding a great economy of processing time and the accuracy of decision. The method was applied to recognition of handwritten English letters and Japanese Katakana's with success. The method is also universal and can be applied to any category of distorted pattems.


Ex vivo foam cell formation is enhanced in monocytes from older individuals by both extrinsic and intrinsic mechanisms.
Aging is the strongest predictor of cardiovascular diseases such as atherosclerosis, which are the leading causes of morbidity and mortality in elderly men. Monocytes play an important role in atherosclerosis by differentiating into foam cells (lipid-laden macrophages) and producing atherogenic proinflammatory cytokines. Monocytes from the elderly have an inflammatory phenotype that may promote atherosclerotic plaque development; here we examined whether they are more atherogenic than those from younger individuals. Using an in vitro model of monocyte transmigration and foam cell formation, monocytes from older men (median age [range]: 75 [58-85] years, n=20) formed foam cells more readily than those of younger men (32 [23-46] years, n=20) (P<0.003) following transmigration across a TNF-activated endothelial monolayer. Compared to young men, monocytes from the elderly had impaired cholesterol efflux and lower expression of regulators of cholesterol transport and metabolism. Foam cell formation was enhanced by soluble factors in serum from older men, but did not correlate with plasma lipid levels. Of the three subsets, intermediate monocytes formed the most foam cells. Therefore, both cellular changes to monocytes and soluble plasma factors in older men primes monocytes for foam cell formation following transendothelial migration, which may contribute to enhanced atherosclerosis in this population.


Delphinidin 3-rutinoside-rich blackcurrant extract ameliorates glucose tolerance by increasing the release of glucagon-like peptide-1 secretion.
Glucagon-like peptide-1 (GLP-1) is an incretin that is secreted from enteroendocrine L-cells. Dietary factor-stimulation of endogenous GLP-1 is a promising strategy for increasing the action of GLP-1. Recent studies have shown that berries rich in anthocyanins improve insulin sensitivity and reduce the risk of type 2 diabetes. Our previous study found that the anthocyanin delphinidin 3-rutinoside (D3R) significantly increases GLP-1 secretion in GLUTag cells (enteroendocrine L cell line). Blackcurrants are berries that contain high levels of anthocyanins, particularly D3R. Pre-administered blackcurrant extract (BCE) 5 mg/kg body weight (1 mg D3R/kg) significantly ameliorated glucose tolerance after intraperitoneal glucose injection in rats by stimulating the secretion of GLP-1 and subsequently inducing insulin secretion. D3R did not break down significantly in the gastrointestinal tract for at least 45-60 min after BCE was administered, suggesting that BCE-induced GLP-1 secretion is mainly mediated by D3R and not its degradation products. These findings demonstrate the novel biological function of D3R-rich BCE as a GLP-1 secretagogue. An increase in endogenous GLP-1 secretion induced by BCE may help to reduce the dosages of diabetic medicines and prevent diabetes.


Muscle artifacts in the sleep EEG: automated detection and effect on all-night EEG power spectra.
Owing to the use of scalp electrodes in human sleep recordings, cortical EEG signals are inevitably intermingled with the electrical activity of the muscle tissue on the skull. Muscle artifacts are characterized by surges in high frequency activity and are readily identified because of their outlying high values relative to the local background activity. To detect bursts of myogenic activity a simple algorithm is introduced that compares high frequency activity (26.25-32.0 Hz) in each 4-s epoch with the activity level in a local 3-min window. A 4-s value was considered artifactual if it exceeded the local background activity by a certain factor. Sensitivity and specificity of the artifact detection algorithm were empirically adjusted by applying different factors as artifact thresholds. In an analysis of sleep EEG signals recorded from 25 healthy young adults 2.3% (SEM: 0.16) of all 4-s epochs during sleep were identified as artifacts when a threshold factor of four was applied. Contamination of the EEG by muscle activity was more frequent towards the end of non-REM sleep episodes when EEG slow wave activity declined. Within and across REM sleep episodes muscle artifacts were evenly distributed. When the EEG signal was cleared of muscle artifacts, the all-night EEG power spectrum showed significant reductions in power density for all frequencies from 0.25-32.0 Hz. Between 15 and 32 Hz, muscle artifacts made up a substantial part (20-70%) of all-night EEG power density. It is concluded that elimination of short-lasting muscle artifacts reduces the confound between cortical and myogenic activity and is important in interpreting quantitative EEG data. Quantitative approaches in defining and detecting transient events in the EEG signal may help to determine which EEG phenomena constitute clinically significant arousals.


Genetic analysis of Pseudomonas aeruginosa by pulsed field gel electrophoresis.
We identified the serotypes and genomes patterns of 100 strains of Pseudomonas aeruginosa (P. aeruginosa) that had been isolated from patients who were admitted to the hospital of the Fukui Medical School between 1992 and 1995. A monoclonal diagnostic kit was used to identify the serotypes. Genome patterns were determined by pulsed field gel electrophoresis (PFGE). Serotypes A, B, C, D, E, F, G and I exhibited distinct genome patterns. Differences in genome patterns were also observed in strains of serotypes E and G, depending on the types of clinical samples collected and/or the area of the hospital from which they were isolated. Many of the multiple antibiotic-resistant strains of P. aeruginosa exhibited serotype E. The genome pattern differed between strains that were susceptible vs. resistant to multiple antibiotics. The latter strains exhibited similar genome patterns regardless of their origin. These findings suggest that analysis of genome patterns is important for identifying the origin of nosocomial infection caused by P. aeruginosa, serotype E.