Hypothalamic expression of snoRNA Snord116 is consistent with a link to the hyperphagia and obesity symptoms of Prader-Willi syndrome.
The hypothalamus is integral to the regulation of body homeostasis, including food intake, energy balance, and blood pressure. Dysfunction of the hypothalamus has been associated with a broad range of disorders; many of which are sex-dependent in prevalence. Small nucleolar (sno) RNAs are a group of small RNAs located in nucleoli that modulate chemical modifications and maturation of ribosomal or other RNAs. Recent data suggest that snoRNA Snord116 is important for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia and obesity. The current study was conducted to assess a potential cellular link between Snord116 and phenotypes of PWS. Data from mice revealed Snord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally. These results provide a new lead for understanding the mechanism(s) related to hyperphagia and obesity symptoms in PWS patients.


Emotions and coping methods of Turkish parents of children with cancer.
This hermeneutic phenomenological study was conducted with the aim to determine the emotions and coping methods of Turkish parents whose children were diagnosed with cancer. Data were collected through in-person, in-depth interviews with 12 parents (8 mothers, 4 fathers). The semi-structured interview form was developed based on Elisabeth Kübler-Ross's model of the five stages of grief (denial, anger, bargaining, depression and acceptance) with the addition of questions on coping methods. Data interpretation proceeded through three phases: superficial reading, structural analysis and comprehensive understanding. All the parents made statements indicating their devastation while expressing their feelings at the moment they learned of the diagnosis. After overcoming the first shock, most thought it was a false diagnosis, and some thought it was a test from God. The parents were angry mostly with the doctors, themselves, their spouses and God. All the parents participating in the study stated that they had regrets about the past. Most engaged in more emotion-oriented and fewer problem-focused coping efforts. However, some parents used negative coping methods. These parents need help from healthcare professionals to come to terms with their grief.


Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.
Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus. This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.


Rotational alignment of femoral component between custom cutting block and conventional technique in total knee arthroplasty.
Rotation of femoral components could be optimized to improve function and durability of the knee joint. The purpose of the present study was to assess rotational alignment of femoral component comparing between CT-based, custom cutting blocks and the contemporary total knee arthroplasty, instrument technique. The prospective control study of 80 patients underwent total knee arthroplasty by using PFC Sigma PS total knee design. Rotation offemoral component was analyzed in all patients using postoperative CT scan. Forty patients were perfonned on by using CT-based, patient-specific cutting blocks with femoral rotational axis relative to transepicondylar axis while forty patients were performed on by using contemporaly instrumentation with alignment at 3 degrees external rotation from posterior condylar line. The rotation of the femoral component with external rotation ofmore than 3 degrees or internal rotation was considered outlier. There was no statistically significant difference among ages, gender; BMI, pre-operative mechanical axis between the two groups. There were eleven outliers in conventional group (range, 5 degrees ofexternal rotation to 3 degrees of internal rotation), three femoral components were in excessive external rotation with the angle of more than 3 degrees and eight femnoral components were in internal rotation. In contrast with custom cutting block group was no outliers offemoral rotation. The average rotational alignment was 1.040 +/- 0.62 external rotation from epicondylar axis in custom cutting group and 1.58 +/- 1.750 in contemporary group. Custom cutting, block technique significantly reduced the outlier of the femoral component rotation and aided in positioning of the femoral component in optimal alignment. The improvement of femoral rotation showed no difference in clinical outcome between the two groups.


Chloroquine and Hydroxychloroquine Are Novel Inhibitors of Human Organic Anion Transporting Polypeptide 1A2.
Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used to treat malaria and inflammatory diseases, long-term usage of which often causes severe side effects, especially retinopathy. Solute carrier transporters (SLCs) are important proteins responsible for the cellular uptake of endogenous and exogenous substances. Inhibitors competing with transporter substrates for SLCs often results in unfavorable toxicities and unsatisfactory therapeutic outcomes. We investigated the inhibitory effect of CQ and HCQ on substrate uptake mediated through a range of important SLC transporters in overexpressing human embryonic kidney (HEK293) cells. Our data revealed that both CQ and HCQ potently inhibit the uptake activity of organic anion transporting polypeptide 1A2 (OATP1A2). We recently reported OATP1A2 to be expressed in human retinal pigment epithelium (RPE), where it mediates cellular uptake of all-trans-retinol (atROL), a key step in the classical visual cycle. In this study, we demonstrate that CQ and HCQ could markedly impair atROL uptake in OATP1A2-expressing HEK293 cells and more importantly, in primary human RPE cells. Our study shows that CQ and HCQ are novel inhibitors of OATP1A2 and significantly impair OATP1A2-mediated substrate uptake, particularly transport of atROL into the RPE. This effect may compromise the function of the classic visual cycle leading to vision impairment and contribute to the retinopathy observed clinically in patients using CQ or HCQ.


Energetics of codon-anticodon recognition on the small ribosomal subunit.
Recent crystal structures of the small ribosomal subunit have made it possible to examine the detailed energetics of codon recognition on the ribosome by computational methods. The binding of cognate and near-cognate anticodon stem loops to the ribosome decoding center, with mRNA containing the Phe UUU and UUC codons, are analyzed here using explicit solvent molecular dynamics simulations together with the linear interaction energy (LIE) method. The calculated binding free energies are in excellent agreement with experimental binding constants and reproduce the relative effects of mismatches in the first and second codon position versus a mismatch at the wobble position. The simulations further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with the Phe UUU codon. It is also found that the ribosome significantly enhances the intrinsic stability differences of codon-anticodon complexes in aqueous solution. Structural analysis of the simulations confirms the previously suggested importance of the universally conserved nucleotides A1492, A1493, and G530 in the decoding process.


Body mass index as predictor for body fat:comparison between Chinese and Dutch adult subjects.
The relation between body mass index (kg/m2) and body fat from body density was compared in a group of Chinese and Dutch healthy subjects in relation to sex and age. The Dutch group was selected in relation to the Chinese group in that age, weight, height and body mass index did not exceed the maximal observed values of the Chinese subjects. Mean weight, height and body mass index was higher in the Dutch group, but body fat from density did not differ between the groups. Body fat predicted from body mass index, age and sex did not differ from the value obtained by densitometry in both countries. The correlation between measured body fat and predicted body fat was 0.84 (p<0.01) in the Chinese and 0.90 (p<0.01) in the Dutch. The difference between measured and predicted body fat was related to the level of body fatness (r=0.55, p<0.01), but did not differ between the countries. In different age groups there were slight differences in the measured minus predicted values of the countries, but these differences were less after correcting for differences in the level of body fatness in each age group. It is concluded that the relation between body fatness and body mass index is not different between the two studied populations.


Sucrose synthase activity is not required for cellulose biosynthesis in Arabidopsis.
Biosynthesis of plant cell walls requires UDP-glucose as the substrate for cellulose biosynthesis, and as an intermediate for the synthesis of other matrix polysaccharides. The sucrose cleaving enzyme sucrose synthase (SUS) is thought to have a central role in UDP-glucose biosynthesis, and a long-held and much debated hypothesis postulates that SUS is required to supply UDP-glucose to cellulose biosynthesis. To investigate the role of SUS in cellulose biosynthesis of Arabidopsis thaliana we characterized mutants in which four or all six Arabidopsis SUS genes were disrupted. These sus mutants showed no growth phenotypes, vascular tissue cell wall defects, or changes in cellulose content. Moreover, the UDP-glucose content of rosette leaves of the sextuple sus mutants was increased by approximately 20% compared with wild type. It can thus be concluded that cellulose biosynthesis is able to employ alternative UDP-glucose biosynthesis pathway(s), and thereby the model of SUS requirements for cellulose biosynthesis in Arabidopsis can be refuted.


[Urinary excretion of adrenaline, noradrenaline and 11-hydroxycorticoids under job stress (author's transl)].
The role of the sympathoadrenomedullary and adrenocortical systems has been assessed by measuring serially the urinary excretion of free adrenaline, noradrenaline and 11-hydroxycorticosteroids in 32 healthy men under two conditions of job stress: piece-work and assembly line. The urinary levels of two catecholamines and 11-hydroxycorticosteroids rose significantly in piece work and assembly line workers, compared with the values observed respectively during salaried and "ordinary" work. Identical results were obtained in the same workers after six months of stressor exposure to piece-work and assembly line conditions. The results support the assumption that long-term exposure of conditions of work stress significant effects on the function under study, this being in the same direction and of the same order of magnitude as that described during short-term exposure in other types of every-day stress and distress. The methodological and clinical implication of these results are discussed.


[The hepatitis C problem in transfusions in military medicine].
The article contains data on viral hepatitis C, its etiological factor, epidemiology, methods of diagnosis and prophylaxis. It's high time to conduct 100% screening control of donors for viral hepatitis C antibody, using national test system of fermental analysis. The authors worked out the method of "dry drop" to study the serum for hepatitis C virus antibody.


Comparison of plasma and urinary methods for the direct measurement of the thyroxine to 3,5,3' - triiodothyronine conversion rate in man.
A further development of a new method recently proposed for the direct measurement of the conversion ratio (CR) of T4 to T3 in man is presented. [125I]T4 and [131I]T3 are injected simultaneously, and Sephadex chromatography is performed on urine samples to determine [125I]T3 formed in vivo, while plasma samples are used to measure the injected tracers. CR is calculated with the assumption that urinary [125I]T3 closely reflects [125I]T3 appearing in plasma after the injection of precursor [125I]T4. Four normal subjects and six patients with various thyroid disorders were studied using this method. The experimental data were also analyzed by our previous method based on plasma sampling only and by two recently described methods based on urinary measurements. These comparisons were made in an attempt to ascertain whether there is any systematic difference between the conversion values derived from plasma data and those derived from urinary data. Using plasma data alone, the CR was 28.6 +/- 3.4% (mean +/- SEM) in a group of four normal subjects, 37%, in two untreated hypothyroid patients, 40.2% in one hypothyroid subject receiving T4 treatment, 30.9% in one hyperthyroid patient, 24.9% in one patient with selective hyperthyroxinemia due to amiodarone treatment, and 10.7% in one normal subject after iopanoic acid administration. These values were in excellent agreement with those obtained by the modified procedure described here, in which both urinary and plasma measurements are used. Of the methods using urinary data alone, however, one gave similar results, while the other systematically overestimated the CR, possibly due to delayed excretion of labeled T4 metabolites into the urine. We conclude that 1) the analytical procedure to separate the labeled tracers and metabolites in urine or plasma is critical for the accurate estimation of CR; 2) when an adequate separation procedure is available, plasma and urinary methods for measuring CR yield comparable results; and 3) the plasma method should be used when, in addition to CR, other kinetic (distribution and turnover) parameters of T4 and T3 metabolism are to be estimated.


MicroRNA-486-3p functions as a tumor suppressor in oral cancer by targeting DDR1.
Discoidin domain receptor-1 (DDR1) tyrosine kinase is highly expressed in a variety of human cancers and involved in various steps of tumorigenesis. However, the precise mechanisms underlying the abnormal expression of DDR1 in oral squamous cell carcinoma (OSCC) has not been well investigated. The expression of DDR1 on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-486-3p and DDR1 were accessed by MTT and Annexin V analyses using gain- and loss-of-function approaches. Chromatin immunoprecipitation (ChIP) and methylation specific PCR (MSP) were performed to explore the molecular mechanisms by arecoline treatment. Here, we reported that DDR1 was significantly upregulated in OSCC tissues and its levels were inversely correlated with miR-486-3p expression. The experimental results in vitro confirmed that miR-486-3p decreased DDR1 expression by targeting the 3'-UTR of DDR1 mRNA. Overexpression of miR-486-3p led to growth inhibition and apoptosis induction with a similar function by knockdown of DDR1. Aberrant methylation of ANK1 promoter was a highly prevalent in OSCC and contributes to oral carcinogenesis by epigenetic silencing of ANK1 and miR-486-3p. We found that miR-486-3p can be transcriptionally co-regulated with its host gene ANK1 through epigenetic repression. DNA methylation inhibitor treatment re-expressed ANK1 and miR-486-3p. Importantly, arecoline, a major betel nut alkaloid, recruited DNMT3B binding to ANK1 promoter for DNA methylation and then attenuated the expression of miR-486-3p in OSCC. This study was the first to demonstrate that betel nut alkaloid may recruit DNMT3B to regulate miR-486-3p/DDR1 axis in oral cancer andmiR-486-3p and DDR1 may serve as potential therapeutic targets of oral cancer.


Control of protein synthesis in Escherichia coli: strain differences in control of translational initiation after energy source shift-down.
We have studied the parameters of protein synthesis in a number of Escherichia coli strains after a shift-down from glucose-minimal to succinate-minimal medium. One group of strains, including K-12(lambda) (ATCC 10798) and NF162, showed a postshift translational yield of 50 to 65% and a 2- to 2.5-fold increase in the functional lifetime of general messenger ribonucleic acid. There was no change in the lag time for beta-galactosidase induction in these strains after the shift-down. A second group, including W1 and W2, showed no reduction in translational yield, no change in the functional lifetime of messenger ribonucleic acid, and a 50% increase in the lag time for beta-galactosidase induction. Evidence is presented which indicates that this increased lag time is not the result of a decreased rate of polypeptide chain propagation. A third group of strains, including NF161, CP78, and NF859, showed an intermediate pattern: translational yield was reduced to about 75% of normal, and the messenger ribonucleic acid functional lifetime was increased by about 50%. Calculation of the relative postshift rates of translational initiation gave about 0.2, 1.0, and 0.5, respectively, for the three groups. There was no apparent correlation between the ability to control translation and the genotypes of these strains at the relA, relX, or spoT loci. Measurements of the induction lag for beta-galactosidase during short-term glucose starvation or after a down-shift induced by alpha-methylglucoside indicated that these regimens elicit responses that are physiologically distinct from those elicited by a glucose-to-succinate shift-down.


Clinical evaluation of a samarium compound filter and E-speed film.
Producing radiographs of good diagnostic quality while keeping the dose as low as possible is the goal of the dental radiographer. Rare earth compound filters reduce the dose, but few clinical studies have evaluated the diagnostic yield. The diagnostic quality of a samarium compound filter used with E-speed film was compared with that of a conventional aluminum filter used with E-speed film. Bitewing projections with the test and standard filters were exposed for 39 patients. Agreement was evaluated with kappa statistics. The results indicated a substantial level of agreement between the two filter types. The combination of samarium compound filter and E-speed film appears to be a good mechanism for achieving dose reduction without compromising the diagnostic yield of the film.


Characterization of cimetidine transport in LLCPK1 cells.
In this study, cimetidine uptake and its regulation by LLCPK1 monolayers were investigated. Uptake was temperature dependent with kinetic and specificity characteristics typical of a carrier-mediated mechanism. With cimetidine uptake in the presence of an excess concentration of the potent inhibitor quinidine as a measure of nonspecific transport, the estimated kinetic parameters for cimetidine uptake at 37 degrees C under steady-state conditions are Km = 32.3 +/- 6.4 microM and Vmax = 20.2 +/- 2.1 pmol/mg per minute. Amiloride, quinidine, and quinine inhibited cimetidine uptake, whereas N1-methylnicotinamide, tetraethylammonium, and guanidine did not. The uptake of cimetidine was increased in the presence of a cell-->lumen H+ gradient, consistent with the behavior of a cimetidine-H+ antiport system. Furthermore, the activity of both the Na(+)-H+ exchanger and H(+)-ATPase acted to dissipate the cell-->lumen H+ gradient, thereby decreasing net cimetidine transport. These results suggest that there is a cimetidine-H+ exchange system in LLCPK1 cells and that the net secretion of organic base in vivo may be regulated by luminal acidification mechanisms.


Kansas Board of Nursing position statement on multistate regulation of nurses.
The Kansas State Board of Nursing cannot support multistate licensure under the current interstate compact language. Because each state determines the qualifications for the practice of nursing, the Kansas Attorney General believes the nurse licensure compact in its present form would be an unconstitutional delegation of legislative authority. Other practical issues of concern are the privacy and confidentiality of shared information, the ability to discipline licenses, the Board's ability to provide the information needed for the operation of the system, and lastly the cost to all licensees.


Thermoacoustic tomography--consistency conditions and the partial scan problem.
Hybrid imaging techniques using either radiofrequency (RF) or near-infrared radiation (NIR) as excitation energy measure averages of tissue RF/NIR absorptivity over spheres centred at ultrasound (US) transducer locations on the bottom of a spherical bowl, where [z < 0]. Inversion formulae for the 'complete data' case where transducers measure all over the bowl weight data from the lower hemisphere more heavily for reconstructions points also satisfying (z < 0]. We derive consistency conditions for the data and use them to compute the unmeasured data corresponding to transducer locations on the top of the bowl. This process is clearly unstable, but somewhat tempered by the reconstruction's l/r weighting.


Macroscopic three-dimensional particle location using stereoscopic imaging and astigmatic aberrations.
This Letter presents a stereoscopic imaging concept for measuring the locations of particles in three-dimensional space. The method is derived from astigmatism particle tracking velocimetry (APTV), a powerful technique that is capable of determining 3D particle locations with a single camera. APTV locates particle xy coordinates with high accuracy, while the particle z coordinate has a larger location uncertainty. This is not a problem for 3D2C (i.e., three dimensions, two velocity components) measurements, but for highly three-dimensional flows, it is desirable to measure three velocity components with similar accuracy. The stereoscopic APTV approach discussed in this report has this capability. The technique employs APTV for giving an initial estimate of the particle locations. With this information, corresponding particle images on both sensors of the stereoscopic imaging system are matched. Particle locations are then determined by mapping the two particle image sensor locations to physical space. The measurement error of stereo APTV, determined by acquiring images of 1-μm DEHS particles in a 40 mm×40 mm×20 mm measurement volume in air at Δxyz→0 between two frames, is less than 0.012 mm for xy and 0.025 mm for z. This error analysis proves the excellent suitability of stereo APTV for the measurement of three-dimensional flows in macroscopic domains.


Treatment of wastewater containing acid rose red dye by biologically aerated filter after chemical oxidation.
Combined processes of pre-chemical oxidation and biological aerated filter (BAF) were used to treat wastewater containing non-biodegradable acid rose red dye. Advance oxidation processes (AOPs) of ozone and Fenton reagent were applied for pre-chemical oxidation, which reduced the degree of color and organic matter simultaneously increasing the biodegradability of the wastewater. The majority of the organic matter was removed by BAF. When using ozone as pre-chemical oxidation, the operation is simpler. The combined processes of AOPs, including ozone and Fenton reagent, followed by BAF reduced the color and chemical oxygen demand (COD) to less than 20 degrees and 40 mg l(-1), respectively from the influent concentration of about 4000 degree color and 300 mg l(-1) COD. The effluent water quality could meet the required standard for grey water reuses.


Genetic diversity, inbreeding and cancer.
Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer.


Peptide-functionalized iron oxide magnetic nanoparticle for gold mining.
Here, we present our work on preparing a novel nanomaterial composed of inorganic binding peptides and magnetic nanoparticles for inorganic mining. Two previously selected and well-characterized gold-binding peptides from cell surface display, AuBP1 and AuBP2, were exploited. This nanomaterial (AuBP-MNP) was designed to fulfill the following two significant functions: the surface conjugated gold-binding peptide will recognize and selectively bind to gold, while the magnetic nano-sized core will respond and migrate according to the applied external magnetic field. This will allow the smart nanomaterial to mine an individual material (gold) from a pool of mixture, without excessive solvent extraction, filtration, and concentration steps. The working efficiency of AuBP-MNP was determined by showing a dramatic reduction of gold nanoparticle colloid concentration, monitored by spectroscopy. The binding kinetics of AuBP-MNP onto the gold surface was determined using surface plasmon resonance (SPR) spectroscopy, which exhibits around 100 times higher binding kinetics than peptides alone. The binding capacity of AuBP-MNP was demonstrated by a bench-top mining test with gold microparticles. Graphical abstract.


[Autoinflammatory bone disorders in childhood].
Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disease with unpredictable, painful courses of osteolytic lesions in the bones. CNO is frequently associated with psoriasis and inflammatory bowel disease. In cases with multifocal lesions the term chronic recurrent multifocal osteomyelitis (CRMO) is preferably used. SAPHO (synovitis, acne, pustulosis palmoplantaris, hyperostosis and osteitis) syndrome is regarded as CRMO in adults. New knowledge of the hereditary forms like Majeed syndrome, deficiency of IL-1-receptor antagonist and cherubism is described.


Morphological changes in the pancreas and glucose reduction of the aqueous extract of Costus afer leaf on alloxan-induced diabetic rats.
Considering the antihyperglycemic and antioxidant activities of herbs, this study has evaluated the morphological changes, hypoglycemic effect, and comparative ameliorating effects of Costus afer Ker Gawl leaf and glibenclamide on pancreatic injury induced by alloxan. Thirty adult male albino rats that were divided into six groups of five weight-matched animals each were used in the study. Groups 1 and 2 served as controls, whereas groups 3-6 were alloxan-induced diabetic groups treated with different doses of the extract (375, 750, and 1125 mg/kg C. afer) and glibenclamide, respectively. The glucose level was measured daily, whereas the weight of the animal was monitored on a weekly basis for 21 days. The oral glucose tolerance test was measured on overnight fasted rats after glucose load at 0, 30, 60, 90, and 120 min. The histopathology of the pancreas was also investigated. The phytoconstituents of C. afer Ker Gawl leaves include glycosides, tannins, saponins, terpenoid, phenolic compound, flavonoids, and alkaloids. Costus afer possessed significant hypoglycemic (p<0.05) effect and reversed the histopathologic damage of pancreases in alloxan-induced diabetic rats comparable to those of glibenclamide. Costus afer leaves possess both antidiabetic and tissue protective properties on pancreases of investigated rats.


Macromolecular beta-adrenergic antagonists discriminating between receptor and antibody.
The beta-adrenergic antagonist, alprenolol, was attached in an irreversible manner to macromolecular dextran via side arms that differed in length. The ability of these macromolecules to bind to the beta-adrenergic receptor of frog erythrocytes and to catecholamine-binding antibodies raised against partially purified receptors was studied. Compared to the parent drug the potency of binding of macromolecular alprenolol to the receptor decreased about 1/10, 1/600, and 1/8000 when the length of the arm separating alprenolol from the dextran moiety was 13, 8, and 4 atoms, respectively. In contrast, the binding potencies of the parent drug and of all its macromolecular derivatives for the antibody were within the same order of magnitude. Thus, conversion of a drug to a macromolecular form may not only sustain its binding activity but may also lead in a higher selectivity. The macromolecular derivatives described here may be suitable probes for investigation of the location and of the molecular properties of the binding sites for beta-adrenergic drugs.


Pharmacological effect of a new idebenone formulation in a model of carrageenan-induced inflammatory pain.
Considerable evidence demonstrated that the central role of reactive oxygen species and reactive nitrogen species (ROS and RNS) in the development of thermal hyperalgesia is associated to acute and chronic inflammation. Idebenone (IDE), a synthetic analogue of the endogenous cellular antioxidant coenzyme Q10 (CoQ10), is an active drug in the central nervous system which shows a protection in a variety of neurological disorders. Since it is lipophilic, poorly water soluble and highly bound to plasma proteins, different technological approaches have been explored to increase its solubility and new pharmaceutical properties. Therefore, it has been complexed with HP-β-cyclodextrins (HP) and its efficacy has been assessed in an animal model of carrageenan-induced thermal hyperalgesia. All male rats used for this study received a subplantar injection of carrageenan into the right hindpaw in the presence or absence of IDE alone and IDE/HP complex. We observed that IDE poorly reduced painful carrageenan effects whereas IDE/HP complex was able to prevent carrageenan-induced hyperalgesia and edema in a dose-dependent manner, reducing spinal MDA levels and protein nitration. Hence, our results demonstrated that when complexed with HP, idebenone exerts a potent analgesic and anti-inflammatory efficacy.


Pigment-epithelium-derived factor is upregulated in photocoagulated human retinal pigment epithelial cells.
There is much evidence that pigment-epithelium-derived factor (PEDF) is a potent antiangiogenic cytokine which inhibits retinal and choroidal neovascularization by inducing apoptosis in activated vascular endothelial cells. Furthermore, the regulation of PEDF appears to be linked to the regulation of vascular endothelial growth factor (VEGF), one of the most potent inducers of intraocular neovascularization. Previous studies have established that thermal photocoagulation, the mainstay in the therapy of various neovascular diseases of the posterior segment, results in a decrease in intraocular concentrations of VEGF and other angiogenic growth factors, thereby inhibiting active retinal neovascularization. In the current study, we sought to determine whether thermal photocoagulation has the potential to regulate the expression of PEDF in human retinal pigment epithelial (RPE) cells. Cultures of RPE cells were photocoagulated with a 532-nm diode laser. Subsequently, RNA was isolated for RT-PCR, and whole-cell extracts and precipitated cell culture supernatant were subjected to Western blot analysis. According to our results, PEDF mRNA and protein are significantly upregulated after photocoagulation. Moreover, PEDF protein was found to be secreted in the cell culture medium.


Angiography and MR-angiography in the diagnosis of peripheral arterial occlusive disease in diabetic patients.
An invasive diagnostic procedure as angiography which involves direct arterial injection of contrast through suitable catheters, is still considered the gold standard in the evaluation of diabetic patients with peripheral arterial occlusive disease. The accuracy of anatomical details is combined on angiography with a pan view, indispensable for correct therapeutic planning. MR-angiography, with the 2D time of flight sequences in particular, supplies images of great anatomical accuracy and very sensitive in the detection of occlusive lesions which compare well with angiography and superior in the assessment of the length of occluded tracts. This noninvasive, cost-effective procedure seems bound to replace angiography in the pretreatment evaluation of diabetic patients with peripheral arterial occlusive disease.


Dolichopodidae of riverbeds and springs in Croatia with an updated checklist of Croatia (Diptera).
Several invertebrate surveys in Croatia conducted between 2005 and 2014 and including; e.g., Plitvice Lakes, produced 123 bycatch samples of Dolichopodidae (Diptera) from 68 sampling sites collected at 36 localities in seven counties. Seventy-seven were retrieved from emergence traps, six from pan traps and 40 were collected with sweep net and/or aspirator. They contained 420 dolichopodid flies that belonged to 64 species in 22 genera. Four species, Campsicnemus umbripennis, Hercostomus chetifer, Liancalus virens and Syntormon pallipes, accounted for over half of the yields. Contrary to most species that were found in largest numbers in rivers, and their beds in particular, S. pallipes and Hercostomus gracilis were considerably more abundant at springs. Fifty-five species could be added to the national checklist which raises the total number to 94 species. All species records are given, the habitat of each species is described, if possible, and taxonomic notes are provided for some dubious species. Finally, elements are presented to support the assumption that the extant dolichopodid species richness of Croatia is at least three- to fourfold of the current number.


Long-time dynamics of concentrated charge-stabilized colloids.
Dynamic light scattering was used to study the dynamic structure factor, S(q,t), of suspensions of charged colloidal silica spheres over the full colloidal time range. We show that a dynamic scaling relation for S(q,t) found by Segrè and Pusey [Phys. Rev. Lett. 77, 771 (1996)10.1103/PhysRevLett.77.771] for hard spheres, relating long-time and short-time dynamics, and collective and self-diffusion, also applies to charged colloids up to the freezing concentration. The universality of this scaling is analyzed theoretically. Our experimental data confirm dynamic freezing criteria proposed for the long-time self- and cage-diffusion coefficients, along with a theoretical prediction for the self-diffusion coefficient.


An investigation of dose changes for therapeutic kilovoltage X-ray beams with underlying lead shielding.
Kilovoltage x-ray beams are used to treat cancer on or close to the skin surface. Many clinical cases use high atomic number materials as shielding to reduce dose to underlying healthy tissues. In this work, we have investigated the effect on both the surface dose and depth doses in a water phantom with lead shielding at depth in the phantom. The EGSnrc Monte Carlo code was used to simulate the water phantom and to calculate the surface doses and depth doses using primary x-ray beam spectra derived from an analytical model. The x-ray beams were in the energy range of 75-135 kVp with field sizes of 2, 5 and 8 cm diameter. The lead sheet was located beneath the water surface at depths ranging from 0.5-7.5 cm. The surface dose decreased as the lead was positioned closer to the water surface and as the field size was increased. The variation in surface dose as a function of x-ray beam energy was only small but the maximum reduction occurred for the 100 kVp x-ray beam. For the 8 cm diameter field with the lead at 1 cm depth and using the 100 kVp x-ray beam, the surface dose was reduced to 0.898 of the surface dose in the water phantom only. Measured surface dose changes, using a Farmer-type ionization chamber, agreed with the Monte Carlo calculated doses. Calculated depth doses in water with a lead sheet positioned below the surface showed that the dose fall-off increased as the lead was positioned closer to the water surface as compared to the depth dose in the water phantom only. Monte Carlo calculations of the total x-ray beam spectrum at the water surface showed that the total fluence decreased due to a reduction in backscatter from within the water and very little backscatter from the lead. The mean energy of the x-ray spectrum varied less than 1 keV, with the lead at 1 cm beneath the water phantom surface. As the Monte Carlo calculations showed good agreement with the measured results, this method can be used to verify surface dose changes in clinical situations where measurements are difficult. The clinical impact of the use of lead must be considered in the dose prescription for patients being treated with kilovoltage x-ray beams.


The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A.
S100 proteins comprise a multigene family of EF-hand calcium binding proteins that engage in multiple functions in response to cellular stress. In one case, the S100B protein has been implicated in oligodendrocyte progenitor cell (OPC) regeneration in response to demyelinating insult. In this example, we report that the mitochondrial ATAD3A protein is a major, high-affinity, and calcium-dependent S100B target protein in OPC. In OPC, ATAD3A is required for cell growth and differentiation. Molecular characterization of the S100B binding domain on ATAD3A by nuclear magnetic resonance (NMR) spectroscopy techniques defined a consensus calcium-dependent S100B binding motif. This S100B binding motif is conserved in several other S100B target proteins, including the p53 protein. Cellular studies using a truncated ATAD3A mutant that is deficient for mitochondrial import revealed that S100B prevents cytoplasmic ATAD3A mutant aggregation and restored its mitochondrial localization. With these results in mind, we propose that S100B could assist the newly synthesized ATAD3A protein, which harbors the consensus S100B binding domain for proper folding and subcellular localization. Such a function for S100B might also help to explain the rescue of nuclear translocation and activation of the temperature-sensitive p53val135 mutant by S100B at nonpermissive temperatures.


Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations.
Increasing evidence indicates a role of hyperpolarization activated cation (HCN) channels in controlling the resting membrane potential, pacemaker activity, memory formation, sleep, and arousal. Their disfunction may be associated with the development of epilepsy and age-related memory decline. Neuronal hyperexcitability involved in epileptogenesis and EEG desynchronization occur in the course of dementia in human Alzheimer's Disease (AD) and animal models, nevertheless the underlying ionic and cellular mechanisms of these effects are not well understood. Some suggest that theta rhythms involved in memory formation could be used as a marker of memory disturbances in the course of neurogenerative diseases, including AD. This review focusses on the interplay between hyperpolarization HCN channels, theta oscillations, memory formation and their role(s) in dementias, including AD. While individually, each of these factors have been linked to each other with strong supportive evidence, we hope here to expand this linkage to a more inclusive picture. Thus, HCN channels could provide a molecular target for developing new therapeutic agents for preventing and/or treating dementia.


Modeling of Sustainable Base Production by Microbial Electrolysis Cell.
A predictive model for the microbial/electrochemical base formation from wastewater was established and compared to experimental conditions within a microbial electrolysis cell. A Na2 SO4 /K2 SO4 anolyte showed that model prediction matched experimental results. Using Shewanella oneidensis MR-1, a strong base (pH≈13) was generated using applied voltages between 0.3 and 1.1 V. Due to the use of bicarbonate, the pH value in the anolyte remained unchanged, which is required to maintain microbial activity.


Racial Discrimination in the Life Course of Older Adults Experiencing Homelessness: Results from the HOPE HOME Study.
Over 2.5 million people experience homelessness yearly in the United States. Black persons are overrepresented by three-fold among those experiencing homelessness but little research has examined the relationship between race and homelessness. We aimed to understand the relationship between race and the experience of homelessness for older adults. We used grounded theory methodology to analyze in-depth qualitative interviews (n = 65) of persons experiencing homelessness. We recruited participants who were enrolled in two sub-studies of the Health Outcomes of People Experiencing Homelessness in Older Middle AgE (HOPE HOME) Study in Oakland California. We identified two major themes within interviews with Black participants (n=52) related to race: (1) participants experienced overt racial discrimination in early life and (2) structural racism precipitated and perpetuated adult homelessness. Further, we identified sub-themes of structural racism that contributed to participants becoming or staying homeless: criminal justice discrimination, employment discrimination, exposure to violence, premature death, and limited family wealth. We developed a theoretical model of how these elements of structural racism may increase susceptibility to homelessness. These relationships between racial discrimination and homelessness may serve as targets for policies aimed at preventing homelessness.


Longitudinal changes in brain CT scans and development of dementia in Down's syndrome.
To determine the relationship of the development of dementia to longitudinal changes in brain CT scans in patients with Down's syndrome (DS), we studied 14 Japanese DS patients at an interval of 10 years. The age at entry to the study was 35.7 +/- 9.9 (mean +/- SD) years in 1989 when we did the first CT scans. We performed the second CT scans in 1999 and quantitatively compared them with those taken in 1989. The 4 oldest of the patients (the demented group, 55.3 +/- 1.4 years of age in 1999) developed symptoms of cognitive decline before 1999. The younger 10 (the non-demented group, 41.9 +/- 9.0 years of age in 1999) remained stable in cognitive function until 1999. Despite the clear difference between the demented and the non-demented group in brain atrophy in 1999, CT measures of the demented group were similar to those of the non-demented group in 1989. These results indicate that age is a better predictor of dementia than imaging studies and that CT does not show a quantitative difference between the demented and the non-demented group before the onset of dementia.


Office microlaparoscopy under local anesthesia.
Laparoscopic surgery has been at the forefront of gynecologic surgical innovation in the past decade. Significant benefits which have been realized by the utilization of laparoscopy include: 1) a reduced size of surgical incisions 2) reduced length of hospital stays 3) increased utilization of outpatient surgery 4) a more rapid postoperative recovery period 5) reduced morbidity and 6) reduced total costs of treatment. Recent refinements in surgical technique and instrumentation have allowed for the development of a new incarnation of laparoscopy which has the potential to further realize each of these goals. Office microlaparoscopy under local anesthesia is the most recent advance in gynecologic minimally invasive surgery.


Combined low-dose antimuscarinics for refractory detrusor overactivity in children.
Behavioral therapy and bowel management are the initial and mainstay treatments for overactive bladder (OAB). Antimuscarinic agents are initiated if these measures fail or symptoms are severe. This study reported the results of treatment with a high dosage of a single drug in children with refractory detrusor overactivity (DO). After the children maintained their previous antimuscarinic medication, a second antimuscarinic drug (trospium chloride) was added as a combination therapy. Seventy-two children with DO were enrolled in this prospective study (Figure). They had persistent urgency and urgency urinary incontinence (UUI), even with behavioral bowel therapy, and used an optimized dosage of oxybutynine. All patients demonstrated DO at urodynamic study and started on oxybutynin and trospium chloride at the lowest weight-adjusted dose (10-20 mg/day for trospium chloride). A bladder diary was recorded for 3 days, and urodynamic studies were repeated at 3 and 6 months. Sixteen children (22.2%) became dry. Thirty-three children (45.8%) attained a significant decrease in incontinence from an average of 5 to 1.3 episodes per day. A statistically significant increase of mean cystometeric bladder capacity (P = 0.006) was also observed at the 6-month follow-up. The overall success rate was 68%, since 23 children (32%) discontinued combined treatment due to persistent symptoms and/or intolerable side effects. A total of 41 children (57%) reported no side effects, 25 (34.7%) reported mild side effects, six (8.3%) reported moderate side effects, and two withdrew from the study due to their side effects. The addition of low-dose trospium chloride to oxybutynine seemed to be an effective and safe treatment approach for children with DO who were refractory to high-dosage monotherapy. Different combinations with different antimuscarinics drugs could be evaluated in the future.


Psychosocial influences on mortality after myocardial infarction.
Psychosocial interviews with 2320 male survivors of acute myocardial infarction, participants in the beta-Blocker Heart Attack Trial, permitted the definition of two variables strongly associated with an increased three-year mortality risk. With other important prognostic factors controlled for, the patients classified as being socially isolated and having a high degree of life stress had more than four times the risk of death of the men with low levels of both stress and isolation. An inverse association of education with mortality in this population reflected the gradient in the prevalence of the defined psychosocial characteristics. High levels of stress and social isolation were most prevalent among the least-educated men and least prevalent among the best-educated. The increase in risk associated with stress and social isolation applied both to total deaths and to sudden cardiac deaths and was noted among men with both high and low levels of ventricular ectopy during hospitalization for the acute infarction.


Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.
Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1β levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.


Effects of pre-harvest glyphosate use on protein composition and shikimic acid accumulation in spring wheat.
During wheat cultivation, glyphosate-based herbicides are recommended to be applied a week prior to harvest during the ripe stage of physiological maturity. However, some grains may not be at this physiological stage due to non-uniform maturation within the field. The goal of this study was to determine the effect of glyphosate-based herbicide timing on the chemistry of wheat gluten proteins and shikimic acid accumulation. The results of the study indicate that pre-harvest glyphosate application does not impact the amino acid composition, protein secondary structure or gluten protein composition. However, pre-harvest glyphosate application decreased the molecular weight of SDS extractable and unextractable proteins, and significantly increased the amount of shikimic acid accumulation, especially when applied early. Thus, this study indicates that pre-harvest use of glyphosate-based herbicides can cause significant differences in wheat protein chemistry and shikimic acid levels, especially when applied earlier than recommended, emphasizing the importance of timely application.


Childhood Poverty and the Transition to Adulthood.
The authors used the Panel Study of Income Dynamics 2007 Transition to Adulthood data in combination with the 2002 Child Development Supplement to examine social class bifurcation in young adulthood. Results indicate that poor youth possibly take on adult roles "too early" at the same time that high-income youth may be supported for a long period past their 18th birthday. Although not all evidence is consistent with this bifurcated story, childhood poverty does play a key role. Young adults from poor families establish financial independence early (e.g., contributing to family bills during adolescence, considering themselves fully responsible for their finances as young adults), whereas young adults from more affluent homes are more likely to receive financial transfers from their parents (who often help them pay for college and other expenses). These findings highlight the ways in which socioeconomic inequality in childhood can differentiate youth's experiences of adolescence and young adulthood.


Language and functionality of post-stroke adults: evaluation based on International Classification of Functioning, Disability and Health (ICF).
Cerebrovascular accident is an important Public Health problem because of the high rates of mortality and sequelae such as language disorders. The conceptual health changes have led to the incorporation of functional and social aspects in the assessments as proposed by the World Health Organization in the International Classification of Functioning, Disability and Health. The purpose was to evaluate and classify language aspects, functionality and participation of post-stroke individuals based on the concepts of the International Classification of Functioning, Disability and Health and characterize the sociodemographic profile of participants. Data collection was carried out through the application of a clinical instrument to evaluate language, participation and functionality in fifty individuals based on the International Classification of Functioning, Disability and Health. The age of the participants varied between 32 and 88 years, and the majority were elderly men. Among body functions, the participants reported more difficulties in "memory functions". As for activity and participation, more difficulties were reported in "recreation and leisure". As for environmental factors, the component "healthcare professionals" was indicated as a facilitator by the majority of participants. The results show the impact of language difficulties in the lives of post-stroke adults and reinforce the applicability of the International Classification of Functioning, Disability and Health as an important complementary tool for assessing language, functionality and participation in a comprehensive and humane approach, towards the improvement of health assistance in ambulatory care.


Acute nonlymphocytic leukemia, monocytic variant. Report of a case.
This report documents a case of a patient presenting unusual oral features of one of the rarer variants of acute nonlymphocytic leukemia, a malignancy whose oral manifestations may be the first indication of the presence of an underlying blood dyscrasia. The findings at the initial appointment and the patient's progress for the following 13 months until his death are presented. Initial suspicion of the clinical symptoms and an immediate, subsequent hospital hematology report established the diagnosis. The histologic features of a gingival biopsy taken during the oral examination were strongly suggestive of leukemia. Since the leukemias may imitate other oral conditions, especially various diseases of the periodontium, it is of paramount importance that the dental clinician recognize their clinical manifestations. As future treatment modalities improve, the dental clinician is seeing more leukemic patients in remission as well as more cases that have relapsed.


Linear relations in microbial reaction systems: a general overview of their origin, form, and use.
In microbial reaction systems, there are a number of linear relations among net conversion rates. These can be very useful in the analysis of experimental data. This article provides a general approach for the formation and application of the linear relations. Two type of system descriptions, one considering the biomass as a black box and the other based on metabolic pathways, are encountered. These are defined in a linear vector and matrix algebra framework. A correct a priori description can be obtained by three useful tests: the independency, consistency, and observability tests. The independency are different. The black box approach provides only conservations relations. They are derived from element, electrical charge, energy, and Gibbs energy balances. The metabolic approach provides, in addition to the conservation relations, metabolic and reaction relations. These result from component, energy, and Gibbs energy balances. Thus it is more attractive to use the metabolic description than the black box approach. A number of different types of linear relations given in the literature are reviewed. They are classified according to the different categories that result from the black box or the metabolic system description. Validation of hypotheses related to metabolic pathways can be supported by experimental validation of the linear metabolic relations. However, definite proof from biochemical evidence remains indispensable.


Evaluation of disposable microfluidic chip design for automated and fast Immunoassays.
We report here, the design and development of a disposable immunoassay chip for protein biomarker detection within ∼1 h. The unique design allows for real-time dynamic calibration of immunoassay for multiple biomarker detections on the chip. The limit of detection achieved for this test chip is 10 pg/ml for IL6, and 50 pg/ml for GFAP with a detection time of 1 h. The prototype instrument used for flowing the reagents through the chip can be easily assembled from off-the-shelf components with the final chemiluminescent detection carried out in a commercial plate reader. Optimization of different aspects of chip design, fabrication, and assay development is discussed in detail.


Association between vasectomy and risk of testicular cancer: A systematic review and meta-analysis.
A number of researchers have reported that vasectomy is a risk factor for testicular cancer. However, this conclusion is inconsistent with a number of other published articles. Hence, we conducted this meta-analysis to assess whether vasectomy increases the risk of testicular cancer. We identified all related studies by searching the PubMed, Embase, and Cochrane Library database from January 01, 1980 to June 01, 2017. The Newcastle-Ottawa Scale (NOS) checklist was used to assess all included non-randomized studies. Summarized odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the difference in outcomes between case and control groups. Subgroup analyses were performed according to the study design and country. A total of eight studies (2176 testicular cancer patients) were included in this systematic review and meta-analysis. Six articles were case-control studies, and two were cohort studies. The pooled estimate of the OR was 1.10 (95% CI: 0.93-1.30) based on the eight studies in a fixed effects model. Two subgroup analyses were performed according to the study design and country. The results were consistent with the overall findings. Publication bias was detected by Begg's test and Egger's test and p values > 0.05, respectively. Our meta-analysis suggested that there was no association between vasectomy and the development of testicular cancer. More high-quality studies are warranted to further explore the association between vasectomy and risk of testicular cancer.


Impact of ranolazine on coronary microvascular dysfunction (MICRO) study.
Patients with angina and coronary microvascular dysfunction, without evidence of structural or epicardial coronary disease (Type I CMVD) remain without evidence based treatment options. Previous work has demonstrated that ranolazine can improve angina frequency and stability among patients with Type 1 CMVD; however, the mechanism remains unclear. Therefore, the objective of this pilot project was to assess the impact of ranolazine on Type I CMVD as measured using an invasive tool to measure global resistance (index of microcirculatory resistance (IMR)). Patients with Type 1 CMVD diagnosed using IMR were enrolled and treated with ranolazine 1000mg BID. Coronary angiography and IMR were performed at baseline and on treatment after four weeks. The primary outcome measure was change in IMR pre- and post-treatment. Secondary outcome measures, improvement in angina and activity level, were assessed using the Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI) and Metabolic equivalent for Task (MET) scores. A total of 7 patient were enrolled and completed the study. Mean age was 57.6±7.5, 43% were female and 43% were Hispanic. Mean baseline IMR was 37.25±16.27 which decreased to 19.48±5.69 (p=0.02; (-48% Δ) after treatment with ranolazine. Four of the five SAQ domains improved on treatment with significant improvement in physical limitation (p=0.001), angina frequency (p=0.04), angina stability (p=0.05) and disease perception (p=0.001). Non-significant improvements in activity were also seen in both the DASI and MET scores. Among patients with Type 1 CMVD, our pilot data suggest favorable changes in IMR, anginal symptoms and activity status with ranolazine treatment. These findings support further evaluation of the effects of ranolazine on microcirculatory function and angina symptoms in a larger cohort of patients with Type 1 CMVD.


Dengue virus infection activates cellular chaperone Hsp70 in THP-1 cells: downregulation of Hsp70 by siRNA revealed decreased viral replication.
The pathogenic mechanism of dengue virus infection is related to the host responses within target cells, and therefore we assessed intracellular changes in stress proteins following dengue virus infection. This study provides evidence that Hsp70 helps in viral multiplication by suppressing the type 1 interferon response. Dengue virus infection in human monocytic THP-1 cells led to overexpression of Hsp70, which also acts as a chaperone. The functional role of Hsp70 in dengue virus multiplication was identified by downregulating the Hsp70 gene with its specific siRNA duplexes, which led to a decrease in viral RNA copy numbers in cellular supernatants and intracellular viral load. It also resulted in an increased IFN-α level, which mediates its antiviral effect through double-stranded RNA-induced protein kinase-PKR. Collectively these results suggest that an increased level of Hsp70 expression in dengue-virus-infected THP-1 cells assists in viral replication by escaping the antiviral effect of type 1 interferon.


Tobacco dependence treatment guidelines.
These recommendations are relevant for all clinical fields and all medical professions, although for some more and for some less. Smoking is the cause of every sixth death in the Czech Republic and is related to diseases of all organ systems. Effective treatment for the diagnosis of F17 exists and should be offered and available to approximately 2 million smokers in the Czech Republic as a standard part of medical and preventive care according to time availability - from brief intervention in frame of each clinical contact with the patient to intensive care. It includes psycho-socio-behavioral support and pharmacotherapy. It should cover all professions in clinical medicine - according to WHO recommendations, especially doctors, nurses, pharmacists and dentists and should be reimbursed within health systems. It should also be offered in other services like e.g., social or addictology care. From an economic point of view, it is one of the most cost-effective interventions in medicine.


In situ regeneration of rice (Oryza sativa L.) callus immobilized in polyurethane foam.
An in situ regeneration system for rice calli comprised of a callus growth stage and two regeneration stages was developed. After the first stage of regeneration, the medium is changed and the calli are immobilized in polyurethane foam supports, in each of which 3-5 regenerated plantlets develop from the immobilized calli during the second stage. While no significant change in callus size was observed during the first stage of regeneration, in the second stage callus enlargement and shoot regeneration predominated. In the light of these findings, calli were immobilized in the second stage after medium exchange. The use of 10-mm support cubes with an average pore size of 3.6 mm resulted in the most efficient immobilization and in situ regeneration. Medium exchange after 15 d gave the largest number of support cubes with shoots. When rice calli were cultivated in support cubes placed in 60 ml second-stage medium in a 500-ml flask, the immobilization ratio was 83%, and 82% of the support cubes contained 3-5 regenerated plantlets after 25 d. The shoot lengths of the regenerated plantlets obtained from the in situ regeneration culture were longer than those from a suspension culture. When support cubes with 3-5 regenerated plantlets were transferred from the flask to 1 4 MS solid medium supplemented with 10 g/l sorbitol and 5 g/l sucrose, the regenerated plantlets developed quickly into plants with a length above 10 cm after 10 d.


Novel redispersible nanosuspensions stabilized by co-processed nanocrystalline cellulose-sodium carboxymethyl starch for enhancing dissolution and oral bioavailability of baicalin.
To improve the dissolution and bioavailability of poorly soluble drugs, novel nanosuspensions using co-processed nanocrystalline cellulose-sodium carboxymethyl starch (NCCS) as a synergetic stabilizer were first designed. Co-processed NCCS was prepared by means of homogenization. Poorly soluble baicalin (BCA) was used as a model drug. BCA nanosuspension (BCA-NS/NCCS) using co-processed NCCS as a dispersant was prepared via homogenization and further converted into the dried BCA nanosuspension particle (BCA-NP/NCCS) via spray drying. The influence of NCCS on the dispersion efficiency of BCA-NS/NCCS was investigated. Morphology and crystal characteristic of NCCS and BCA-NP were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of NCCS as a stabilizer for BCA-NS/NCCS and BCA-NP. The optimum 50% concentration of NCCS (nanocrystalline cellulose [NCC]:sodium carboxymethyl starch [SCS]=60:40) could be mostly beneficial for formation and stability of BCA-NS/NCCS. NCCS could completely prevent aggregation of BCA-NP during spray drying and enhance the redispersibility as well as dissolution of spray-dried BCA-NP, which might be attributed to "brick-concrete"-based barrier effect of NCCS and the swelling capacity of superdisintegrant SCS. The crystal state of NCC and BCA presented in BCA-NP/NCCS remained unchanged during the homogenization. The BCA-NP/NCCS exhibited a fast dissolution rate and significantly enhanced bioavailability of BCA. The AUC(0-∞) of the BCA-NP/NCCS (8,773.38±718.18 µg/L·h) was 2.01 times (P<0.05) as high as that of the crude BCA (4,354.61±451.28 µg/L·h). This study demonstrated that novel surfactant-free nanosuspensions could be prepared using co-processed NCCS as a synergetic stabilizer and also provided a feasible strategy to improve the dissolution and oral bioavailability of poorly soluble drug.


Top-down modulation of early print-tuned neural activity in reading.
Fast neural tuning to print has been found within the first 250ms of stimulus processing across different writing systems, indicated by larger N1 negativity in the ERP to words (or characters) compared to control stimuli, such as symbols. However, whether print tuning effects can be modulated by task demands at early stages of visual word recognition is still under debate. To further explore this issue, an ERP study in Chinese was conducted. Familiar, high-frequency, left/right-structured Chinese characters and unfamiliar, stroke number-matched symbols (Korean characters) were used as stimulus conditions. While viewing the characters and symbols, 20 native Chinese speakers performed three tasks: delayed naming, repetition detection, and blue color detection. Results from occipito-temporal and whole map analyses suggest that the influence of task on print tuning changes throughout the N1. Accordingly in the N1 onset, a print tuning main effect was found, with a stronger N1 to words than symbols, irrespective of task. In the N1 offset, a print-by-task interaction reflected a more negative N1 to symbols than words in both delayed naming and color detection, but not in the repetition detection. After the N1 an N2 was observed with task and condition main effects at the whole map level. Taken together, the current study provides evidence that neural tuning to print is modulated by task demands already within the first 250ms, suggesting that early visual-orthographic processing may be less automatic than it was thought, and the possible top-down modulation may be much faster than it was previously assumed.


High levels of serum β2-microglobulin predict severity of coronary artery disease.
The identification of new risk factors for coronary artery disease (CAD) is increasingly sought in an effort to tackle this threatening disease. β2-microglobulin (B2M) is reported to associate with peripheral arterial disease and adverse cardiovascular outcomes. However, the association between B2M and cardiovascular disease remains under-researched. This study evaluated the effects of B2M on CAD without renal dysfunction. One thousand seven hundred sixty-two subjects (403 non-CAD subjects and 1,359 CAD subjects) were investigated. Fasting samples were collected to determine B2M level. The Gensini and SYNTAX scores were used to assess the severity of CAD. CAD subjects were significantly higher in serum B2M level comparing with non-CAD subjects (1.25 ± 0.46 vs 1.14 ± 0.28 mg/L, p < 0.001). Serum B2M level was a risk factor of CAD after adjusting potential confounders (Odds Ratio (OR) = 2.363, 95% confidence interval (CI): 1.467-3.906, p = 0.001). Receiver operating characteristics (ROC) showed B2M level moderately predicted diagnosis of CAD (the area under the ROC curve (AUC) = 0.608, 95% CI: 0.577-0.639, p < 0.001). Furthermore, serum B2M level was positively associated with Gensini score system, SYNTAX score system and the number of disease vessels (NDV ≥ 2). The significant association between serum B2M and CAD suggests that B2M could be a biomarker for CAD.


Enhanced optoelectronic quality of perovskite films with excess CH3NH3I for high-efficiency solar cells in ambient air.
Solution-processed polycrystalline perovskite films contribute critically to the high photovoltaic performance of perovskite-based solar cells (PSCs). The inevitable electronic trap states at grain boundaries and intrinsic defects such as metallic lead (Pb0) and halide vacancies in perovskite films cause serious carrier recombination loss. Furthermore, the film can easily decompose into PbI2 in a moist atmosphere. Here, we introduce a simple strategy, through a small increase in methylammonium iodide (CH3NH3I, MAI), molar proportion (5%), for perovskite fabrication in ambient air with ∼50% relative humidity. Analysis of the morphology and crystallography demonstrates that excess MAI significantly promotes grain growth without decomposition. X-ray photoemission spectroscopy shows that no metallic Pb0 exists in the perovskite film and the I/Pb ratio is improved. A time-resolved photoluminescence measurement indicates efficient suppression of non-radiative recombination in the perovskite layer. As a result, the device yields improved power conversion efficiency from 14.06% to 18.26% with reduced hysteresis and higher stability under AM1.5G illumination (100 mW cm-2). This work strongly provides a feasible and low-cost way to develop highly efficient PSCs in ambient air.


Managing ethical issues in patient care and the need for clinical ethics support.
To investigate the range, frequency and management of ethical issues encountered by clinicians working in hospitals in New South Wales (NSW), Australia. A cross-sectional survey was conducted of a convenience sample of 104 medical, nursing and allied health professionals in two NSW hospitals. Some respondents did not provide data for some questions, therefore the denominator is less than 105 for some items. Sixty-two (62/104; 60%) respondents reported occasionally to often having ethical concerns. Forty-six (46/105; 44%) reported often to occasionally having legal concerns. The three most common responses to concerns were: talking to colleagues (96/105; 91%); raising the issue in a group forum (68/105; 65%); and consulting a relevant guideline (64/105; 61%). Most respondents were highly (65/99; 66%) or moderately (33/99; 33%) satisfied with the ethical environment of the hospital. Twenty-two (22/98; 22%) were highly satisfied with the ethical environment of their department and 74 (74/98; 76%) were moderately satisfied. Most (72/105; 69%) respondents indicated that additional support in dealing with ethical issues would be helpful. Clinicians reported frequently experiencing ethical and legal uncertainty and concern. They usually managed this by talking with colleagues. Although this approach was considered adequate, and the ethics of their hospital was reported to be satisfactory, most respondents indicated that additional assistance with ethical and legal concerns would be helpful. Clinical ethics support should be a priority of public hospitals in NSW and elsewhere in Australia.


Incidental finding of Bochdalek hernia in an adult: a case report.
A Bochdalek hernia, also known as a congenital diaphragmatic hernia (CDH), is a type of hernia that occurs in infants. The diaphragm, the muscle that separates the chest cavity from the abdominal cavity, is characterized by a hole or gap during birth. This opening allows the abdominal organs, such as the stomach, intestines, or liver, to pass through the thoracic cavity. Here, we report a 56-year-old male patient who came to our hospital because of rectal bleeding, symptoms unrelated to the hernia. We performed a Computed Tomography (CT) scan with contrast enhancement to find the cause of the bleeding and as an incidental finding we diagnosed the hernia: it is very rare to find a silent Bochdalek hernia for more than 50 years.


The hunt for a global killer.
As a veterinary student I always felt misplaced. Not until I attended a course in immunology did I really feel the urge and drive to dive into the matter. Almost by coincidence, as a brand new candidate, I had the fortune to get a position in Tuberculosis vaccine research, and never since have I doubted that it was the right choice for me. Since then I have been driven by scientific curiosity and the prospects of generating results that can be used for products for which there is a real need.


Anthropometry and body composition in children.
Changes in body fat, fat-free mass and extracellular water occur in many disorders, and during normal growth in children. Thus, body composition is an increasingly important measurement in paediatric clinical practice, and is used for diagnostic purposes, for decisions for treatment and for monitoring improvement. A number of different methods exist for determining body composition in children; however, their use is complicated by the absence of a gold standard and the lack of validity data in children both with and without growth disorders. In this report, validity and usefulness are compared among anthropometric methods and weighted against other techniques used in children. Recent recommendations of a number of expert committees are discussed.


A simple assessment of lung nodule location for reduction in unnecessary invasive procedures.
CT screening for lung cancer results in a significant mortality reduction but is complicated by invasive procedures performed for evaluation of the many detected benign nodules. The purpose of this study was to evaluate measures of nodule location within the lung as predictors of malignancy. We analyzed images and data from 3,483 participants in the National Lung Screening Trial (NLST). All nodules (4-20 mm) were characterized by 3D geospatial location using a Cartesian coordinate system and evaluated in logistic regression analysis. Model development and probability cutpoint selection was performed in the NLST testing set. The Geospatial test was then validated in the NLST testing set, and subsequently replicated in a new cohort of 147 participants from The Detection of Early Lung Cancer Among Military Personnel (DECAMP) Consortium. The Geospatial Test, consisting of the superior-inferior distance (Z distance), nodule diameter, and radial distance (carina to nodule) performed well in both the NLST validation set (AUC 0.85) and the DECAMP replication cohort (AUC 0.75). A negative Geospatial Test resulted in a less than 2% risk of cancer across all nodule diameters. The Geospatial Test correctly reclassified 19.7% of indeterminate nodules with a diameter over 6mm as benign, while only incorrectly classifying 1% of cancerous nodules as benign. In contrast, the parsimonious Brock Model applied to the same group of nodules correctly reclassified 64.5% of indeterminate nodules as benign but resulted in misclassification of a cancer as benign in 18.2% of the cases. Applying the Geospatial test would result in reducing invasive procedures performed for benign lesions by 11.3% with a low rate of misclassification (1.3%). In contrast, the Brock model applied to the same group of patients results in decreasing invasive procedures for benign lesion by 39.0% but misclassifying 21.1% of cancers as benign. Utilizing information about geospatial location within the lung improves risk assessment for indeterminate lung nodules and may reduce unnecessary procedures. NCT00047385, NCT01785342.


Use of monoclonal antibodies for the diagnosis of cytomegalovirus infection by the detection of early antigen fluorescent foci (DEAFF) in cell culture.
A pool of seven monoclonal antibodies, each reactive with cytomegalovirus (CMV) early antigens, was used in an indirect immunofluorescence method for the rapid detection of CMV-infected fibroblasts following inoculation with clinical specimens. A total of 1,639 specimens were examined, and the results were compared with those of conventional isolation procedures. The detection of CMV by early antigen fluorescent foci (DEAFF) was found to be comparable, both in terms of specificity and sensitivity, to that of conventional cell culture. Its great advantage, however, is the rapidity with which results are achieved. Thus, results were available from the DEAFF test within 24 hours of receipt of the specimens as compared to a mean of 16 days for cell culture. This single rapid assay for the detection of CMV in clinical samples may be performed by any laboratory familiar with cell culture techniques and in our hands is the preferred diagnostic method for CMV.


A Systematic Review of the Impact of Surgical Special Care Units on Patient Outcomes and Health Care Resource Utilization.
Perioperative intermediate care units (termed surgical special care units) have been widely implemented across health systems because they are believed to improve surveillance and management of high-risk surgical patients. Our objective was to conduct a systematic review to investigate the effects of a 3-level model of perioperative care delivery (ie, ward, surgical special care unit, or intensive care unit) compared to a 2-level model of care (ie, ward, intensive care unit) on postoperative outcomes. Our protocol was registered with PROSPERO, the international prospective register of systematic reviews (CRD42015025155). Randomized controlled studies and nonrandomized comparator studies were included. We performed a systematic search of Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, and the Cochrane library (inception - 11/2017). The primary outcome was mortality; secondary outcomes included length of stay and hospital costs. We identified 1995 citations with our search, and 21 studies met eligibility criteria (2 randomized controlled studies and 19 nonrandomized comparator studies; 44,134 patients in total). Surgical special care units were characterized by continuous monitoring (12 studies), the absence of mechanical ventilation (8 studies), nurse-to-patient ratios (range, 1:2-1:4), and number of beds (median: 5; range: 3-33). Thirteen studies reported on mortality. Notable findings included no observed difference in overall in-hospital mortality, but an apparent increase in intensive care unit mortality in a 3-level model of care. This may reflect a decanting of lower acuity patients from the intensive care unit to the surgical special care unit. No significant difference was found in hospital length of stay; however, 2 studies demonstrated reductions in hospital costs with the implementation of a surgical special care unit. Significant clinical and methodological heterogeneity precluded pooled analysis. Given the prevalence of surgical special care units, the results of our review suggest that additional methodologically rigorous investigations are needed to understand the effect of these units on the surgical population.


Predictors of Recurrent Atrial Fibrillation Using Mode Switch Quantification.
The efficacy of mode switching to predict atrial fibrillation has been established in the literature. There have been few studies investigating the incidence and clinical implication of mode switch episodes quantified from implantable cardioverter defibrillator and pacemaker interrogation. We sought to investigate the incidence of mode switch recurrence in patients with implantable cardioverter defibrillators and permanent pacemakers. Mode switch was defined as any occurrence documented during device interrogation after the date of implantation. Clinical predictors (age, gender, hypertension, diabetes, syncope, atrial fibrillation (AF)), and medications were analyzed to determine association with single and recurrent mode switch occurrences. There were 21 patients experiencing a mode switch event, identified from a group of 54 patients (42 males; mean age 70 ± 12 years; mean follow-up 29.1 ± 22 months (3.4 - 81.4 months)). All but two patients were receiving medical therapy including beta blockers, statins, ace-inhibitors, and anti-arrhythmics. There were 21 subjects who experienced at least one mode switch during their follow-up and 33 subjects who never experienced a mode switch during their follow-up time. The median time to first mode switch from device implantation was 39.3 months. Risk factors individually associated with any mode switch episode included: diabetes (DM) (P < 0.04) and use of digitalis (P = 0.02). Subjects who had a history of DM were 5 times more likely to have at least one mode switch occurrence. There was a significantly higher rate of mode switch among patients who were diabetic than patients who were not (3.7 per follow-up month ± 5.3 vs. 0.98 per follow-up month ± 2.02; P = 0.02). There was a significantly higher rate of mode switch among patients who were on digitalis than those who were not (3.1 per follow-up month ± 4.3 vs. 0.73 per follow-up month ± 1.9; P = 0.02). The main factors associated with any mode switch are having a history of diabetes and digitalis use. Those patients who are diabetics and those on digitalis may warrant closer observation and management for the development of atrial fibrillation.


Multi-Gene Prognostic Signatures and Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in ER-positive, HER2-negative Breast Cancer Patients.
Determining which patients with early-stage breast cancer should receive chemotherapy is an important clinical issue. Chemotherapy has several adverse side effects, impacting on quality of life, along with significant economic consequences. There are a number of multi-gene prognostic signatures for breast cancer recurrence but there is less evidence that these prognostic signatures are predictive of therapy benefit. Biomarkers that can predict patient response to chemotherapy can help avoid ineffective over-treatment. The aim of this work was to assess if the OncoMasTR prognostic signature can predict pathological complete response (pCR) to neoadjuvant chemotherapy, and to compare its predictive value with other prognostic signatures: EndoPredict, Oncotype DX and Tumor Infiltrating Leukocytes. Gene expression datasets from ER-positive, HER2-negative breast cancer patients that had pre-treatment biopsies, received neoadjuvant chemotherapy and an assessment of pCR were obtained from the Gene Expression Omnibus repository. A total of 813 patients with 66 pCR events were included in the analysis. OncoMasTR, EndoPredict, Oncotype DX and Tumor Infiltrating Leukocytes numeric risk scores were approximated by applying the gene coefficients to the corresponding mean probe expression values. OncoMasTR, EndoPredict and Oncotype DX prognostic scores were moderately well correlated according to the Pearson's correlation coefficient. Association with pCR was estimated using logistic regression. The odds ratio for a 1 standard deviation increase in risk score, adjusted for cohort, were similar in magnitude for all four signatures. Additionally, the four signatures were significant predictors of pCR. OncoMasTR added significant predictive value to EndoPredict, Oncotype DX and Tumor Infiltrating Leukocytes signatures as determined by bivariable and trivariable analysis. In this in silico analysis, OncoMasTR, EndoPredict, Oncotype DX, and Tumor Infiltrating Leukocytes were significantly predictive of pCR to neoadjuvant chemotherapy in ER-positive and HER2-negative breast cancer patients.


[Selection of Laboratory Procedures to Detect Toxigenic by the 2-Step Method].
The 2-step method is an algorithm to detect toxigenic Clostridium difficile. We herein compared the sensitivities and specificities of an enzyme immunoassay (toxin A/B-EIA), toxigenic culture (TC-EIA), Loop-Mediated Isothermal Amplification assay (LAMP), and Xpert C. difficile (Xpert) with the detection of the toxin B gene by a polymerase chain reaction (PCR). The results obtained showed that the sensitivities and specificities of toxin A/B-EIA, Xpert, TC-EIA, and LAMP were 30 and 100%, 87.2 and 100%, 97.5 and 89.7%, and 95 and 100%, respectively. We also evaluated the turnaround time (TAT) and cost of toxigenic C. difficile detection. Our hospital TAT for toxin A/B-EIA and TC-EIA are 37 min and 5 days, respectively. We estimated the TAT of Xpert, LAMP, and PCR to be 105 min, 5 days, and 6 days, respectively. On the other hand, the cost to detect toxigenic C. difficile increased in the order of TC-EIA, LAMP, Xpert, and PCR. We have never experienced outbreak of Clostridium difficile infection (CDI) in our hospital, and there is less the number of CDI than other place. So we selected TC-EIA that is good sensitivity and low cost per specimen. Hereafter it'll be necessary to solve a problem it takes time, because we have to respond to outbreak of CDI quickly if it happens.


The difficult pediatric airway--a review of new devices for indirect laryngoscopy in children younger than two years of age.
During the last decade, several new look-around-corner or video airway devices have proven useful in clinical adult practice. Only four of them are currently available in sizes that may be used in children younger than 2 years of age: the AIRTRAQ® Disposable Optical Laryngoscope (Prodol Meditec, Vizcaya, Spain), the GlideScope® Video Laryngoscope (Verathon, Bothell, WA, USA), the Storz DCI® Video Laryngoscope (Karl Storz, Tuttlingen, Germany), and the Truview PCD™ Infant (Truphatek, Netanya, Israel). Here, we review the literature and describe the clinical use of each device in this age-group. The four new laryngoscopes are generally effective and may solve many of the problems with difficult intubations in children younger than 2 years of age. The size of the device and the mouth opening it requires determines its usefulness in the smallest infants. Training will be necessary in implementing and deciding when to use the new airway devices, although one of the big challenges of the future will be to maintain the teaching and training of fiber-optic-guided intubations, which remain the gold standard in difficult endotracheal intubations.


Medical devices; immunology and microbiology devices; classification of Plasmodium species antigen detection assays. Final rule.
The Food and Drug Administration (FDA) is classifying Plasmodium species antigen detection assays into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Plasmodium Species Antigen Detection Assays." The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document that will serve as the special control for this device.


[Risk factors for allergic diseases in children aged 0-24 months in the Wuhu urban area, Anhui Province, China].
To investigate the prevalence of allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province and risk factors for allergic diseases. Cluster random sampling was performed to select 600 children aged 0-24 months and their mothers from the Wuhu urban area, and a questionnaire survey was conducted to collect the data of disease history, family history, mothers' conditions during pregnancy, and child-rearing situation. Univariate analysis and multivariate logistic regression analysis were performed for such data. Among the 597 children included in the analysis, 56 (9.4%) were diagnosed with allergic diseases in the past. The univariate analysis showed that the age, use of antipyretic and analgesic drugs, a history of allergy in the father or grandparents, and the consumption of fish, shrimps, crabs, and shellfish during pregnancy were significantly associated with past allergic diseases (P<0.05). The multivariate logistic regression analysis showed that the age and a history of allergy in the father or grandparents were positively associated with past allergic diseases (OR=4.0-4.9, 2.7, and 2.4 respectively; P<0.05), while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy was negatively associated with past allergic diseases (OR=0.3; P<0.05). A family history of allergy is an independent risk factor for allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province, while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy is a protective factor.


Ability of Ultrasonography in Detection of Different Extremity Bone Fractures; a Case Series Study.
Despite radiography being the gold standard in evaluation of orthopedic injuries, using bedside ultrasonography has several potential supremacies such as avoiding exposure to ionizing radiation, availability in pre-hospital settings, being extensively accessible, and ability to be used on the bedside. The aim of the present study is to evaluate the diagnostic accuracy of ultrasonography in detection of extremity bone fractures. This study is a case series study, which was prospectively conducted on multiple blunt trauma patients, who were 18 years old or older, had stable hemodynamic, Glasgow coma scale 15, and signs or symptoms of a possible extremity bone fracture. After initial assessment, ultrasonography of suspected bones was performed by a trained emergency medicine resident and prevalence of true positive and false negative findings were calculated compared to plain radiology. 108 patients with the mean age of 44.6 ± 20.4 years were studied (67.6% male). Analysis was done on 158 sites of fracture, which were confirmed with plain radiography. 91 (57.6%) cases were suspected to have upper extremity fracture(s) and 67 (42.4%) to have lower ones. The most frequent site of injuries were forearm (36.7%) in upper limbs and leg (27.8%) in lower limbs. Prevalence of true positive and false negative cases for fractures detected by ultrasonography were 59 (64.8%) and 32 (35.52%) for upper and 49 (73.1%) and 18 (26.9%) for lower extremities, respectively. In addition, prevalence of true positive and false negative detected cases for intra-articular fractures were 24 (48%) and 26 (52%), respectively. The present study shows the moderate sensitivity (68.3%) of ultrasonography in detection of different extremity bone fractures. Ultrasonography showed the best sensitivity in detection of femur (100%) and humerus (76.2%) fractures, respectively. It had low sensitivity in detection of in intra-articular fractures.


Knowledge of teachers about suicidal behavior in adolescents.
To identify the knowledge of teachers about suicidal behavior in adolescents. Qualitative exploratory-descriptive study conducted in a state school in the municipality of Porto Alegre, RS, Brazil. Twelve teachers participated in the study. Data were collected through semi-structured interviews analyzed using Bardin's Content Analysis. Three categories were built: "Warning signs of suicide", related to the signs identified by the professionals; "Risk factors for suicide", which indicate the reasons that may lead adolescents to present this type of behavior; and "Difficulties in dealing with the behaviors", referring to the behaviors adopted by adolescents and the difficulties of teachers before the theme. It was possible to identify that teachers recognize some signs of suicidal behavior, as well as some risk factors. Nonetheless, it is necessary to qualify them to approach the subject, since they feel insecure to act in more critical moments, thus generating mainly feelings of sadness, guilt and powerlessness.


Judgements of time to contact are affected by rate of appearance of visible texture.
More fine-grained texture becomes visible if the distance between an observer and an object or surface is reduced. This article illustrates with a schematic example that the inverse rate of the relative appearance of visible texture provides information about time to contact if the observer has a constant visual acuity and the texture has a certain scale-independent structure. An experiment is reported in which texture appearance was manipulated. Participants were asked to make forced-choice time-to-contact judgements. A small but significant effect indicates that the judgements were affected by the rate of appearance of the texture. It is concluded that observers use this type of information.


Major depressive disorder and comorbid cardiac disease: is there a depressive subtype with greater cardiovascular morbidity? Results from the STAR*D study.
The authors conducted exploratory analyses to determine whether specific symptoms of major depressive disorder (MDD) are associated with cardiac disease in 4,041 outpatients at baseline in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. MDD was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; depressive symptoms were evaluated with the 30-item Inventory of Depressive Symptomatology, Clinician-Rated; and cardiac disease, with the Cumulative Illness Rating Scale. After adjustments for gender, age, ethnicity, education, and employment status, sympathetic arousal and early-morning insomnia were significantly associated with cardiac disease. Prospective studies are warranted to confirm these results.


Sonoelastography in differentiation of benign and malignant testicular lesion in dogs.
Present study aimed to evaluae the elasticity of tumorous testicular lesions and usefulness of the elastographic examination for diagnosing lesions in the testes. The study was carried out on nine dogs in which tumorous testicular lesions had been found in the ultrasonographic examination. In all the animals examined, the elastographic examination of the lesions was performed and then castration and the histopathological examination of specimens in order to determine the type of the changes. On the basis of the results of the histopathological examination the dogs were divided into two groups: group I--consisted of three dogs in which nonneoplastic testicular lesions were found and group II comprised six dogs in which neoplasic lesions that began in testicular interstitial cells (Leydigoma) were detected. The lesions observed in dogs of group I showed low stiffness (average 11.25 kPa, range 6.1 to 16.4 kPa), whereas the lesions found in dogs of group II were characterized by high stiffness (average 91.85 kPa, range 52.3 to 131.4 kPa). On the basis of a scale proposed by Goodie et al. (2012), the lesions in group I were in the range of SC1, and in turn, the lesions in group II were in the range of SC 3 inverted. Based on the results obtained, it can be stated that the sonoelastographic examination is useful method for the screening diagnostics of testicular lesions.


Regulatory T cells and IL-17-producing cells in graft-versus-host disease.
Graft-versus-host disease (GvHD), a major complication following allogeneic hematopoietic stem cell transplantation, is mediated by donor-derived T cells. On activation with alloantigens expressed on host antigen-presenting cells, naive CD4(+) T cells differentiate into T-helper cell subsets of effector T cells expressing distinct sets of transcriptional factors and cytokines. Classically, acute GvHD was suggested to be predominantly related to Th1 responses. However, we now face a completely different and complex scenario involving possible roles of newly identified Th17 cells as well as Tregs in GvHD. Accumulating data from experimental and clinical studies suggest that the fine balance between Th1, Th2, Th17 and Tregs after transplantation may be an important determinant of the severity, manifestation and tissue distribution of GvHD. Understanding the dynamic process of reciprocal differentiation of regulatory and T-helper cell subsets as well as their interactions will be important in establishing novel strategies for preventing and treating GvHD.