Potency determination of antidandruff shampoos in nystatin international unit equivalents.
A convenient standard microbiological potency determination test for the antidandruff shampoos was developed by adopting the pharmacopoeial microbiological assay procedure of the drug nystatin. A standard curve was drawn consisting of the inhibition zone diameters vs. logarithm of nystatin concentrations in international units using the fungus Saccharomyces cerevisiae (yeast) strain National Collection of Type Culture (NCTC) 1071606 as the test organism. From the standard curve the yeast inhibitory potencies of the shampoos in nystatin international unit equivalents were determined from the respective inhibition zones of the test samples of the shampoos. Under test conditions four shampoo samples showed remarkable fungal inhibitory potencies of 10227, 10731, 12396 and 18211 nystatin international unit equivalents/ml while two shampoo samples had extremely feeble inhibitory potencies 4.07 and 4.37 nystatin international unit equivalents/ml although the latter two products claimed antifungal activity. The potency determination method could be applied to any antidandruff shampoo with any one or a combination of active ingredients.


Self-regulation of intake of polyethylene glycol by sheep fed diets varying in tannin concentrations.
Tannins occur in many plant species, and they often suppress intake by reducing nutrient availability or by causing malaise. Polyethylene glycol (PEG) binds to tannins and may thereby increase the availability of macronutrients and decrease malaise. Supplemental PEG increases intake of tannin-containing plants by sheep, goats, and cattle. Given the strong response to supplemental PEG, we speculated that animals might self-regulate their intake of PEG when offered foods high in tannins. The objective of the first experiment was to determine if the amount of supplemental PEG (0, 25, 50, 75, or 100 g; molecular weight, 3,350) affected intake by lambs of a food (milo-tannin mix) containing 20% quebracho tannin. There was a linear relationship (Y = 272 + 1.2X; R2 = .86; P = .023) between the amount of supplemental PEG ingested and the subsequent intake of milo-tannin food by lambs. The objective of the second experiment was to determine whether lambs self-regulated intake of PEG when fed a ration that contained 0, 5, 10, 15, or 20% quebracho tannin and whether they adjusted their intake of PEG when tannin was removed from the diet. There was a positive relationship between the amount of PEG ingested and intake of food and tannin (P = .0001). Lambs fed high-tannin diets ate more PEG than controls (P = .03). Lambs fed the 20% tannin diet ate the most PEG, and controls ate the least PEG. Tannin limited intake of the diets, but PEG attenuated the response to a great degree (P = .065). Immediately after tannin was removed from the ration, lambs that formerly had been fed the 20% tannin ration ate more PEG than lambs fed the other rations (P = .0075). Ten of the lambs (5 from the 20% tannin group, 1 from the 15% tannin, and 2 each from the 10 and 5% groups) continued to eat PEG for 7 d after tannin was removed from their ration. When they were tested again 6 wk after the trial and offered tannin-free diets, their intake of PEG had decreased.


Changes in diet through adolescence and early adulthood: longitudinal trajectories and association with key life transitions.
Early adulthood is a period associated with poor diet and rapid weight gain. This is also an age of transition, including environmental, social and lifestyle changes which may be associated with changes in diet. We assess longitudinal associations between four early adulthood life transitions (leaving home, leaving education, entering employment, and cohabitation) and changes in consumption of fruit, vegetables, confectionery and sugar-sweetened beverages (SSBs). Participants (n = 1100) from the Norwegian Longitudinal Health Behaviour Study, reported data on diet and life transitions on up to eight occasions from age 14 to age 30. Diet data were self-reported in response to questions on intake of fruit, vegetables, confectionery and sugar-sweetened beverages. Growth models were developed to describe changing intake of each of the four diet indicators with age. Fixed-effects regression models assessed associations between the four life transitions and within-individual changes in diet indicators, with adjustment for the remaining transitions and parenthood. Diet indicators showed quadratic trajectories with age: fruit and vegetable intakes declined from age 14 to ages 23 and 21 respectively, before increasing to age 30. SSB and confectionery intakes increased to age 18, before subsequently decreasing. Leaving the parental home was associated with a decrease in fruit intake of - 0.54 times/week (95% confidence interval (95%CI): -0.87;-0.22) and vegetable intake of - 0.43 times/week (95%CI: -0.70;-0.15). Leaving education was associated with increases in confectionery (0.33 times/week (95%CI: 0.04;0.62)) and SSB intakes (0.49 times/week (95%CI: 0.10;0.87). Leaving home and leaving education are associated with negative changes in diet and may present opportunities for effective diet and obesity intervention. Further study of these transitions is needed to understand the mechanisms mediating associations between life transitions and changes in diet.


Structure and bonding of molecular stirrers with formula B7M2- and B8M2 (M = Zn, Cd, Hg).
In this work, we systematically explored clusters with formula B7M2- and B8M2 (M = Zn, Cd, Hg). The putative global minima are formed by an M2 dimer and a disk-shaped boron wheel. Moreover, the chemical bonding analysis revealed that charge transfer from the metal atoms to the boron motifs resulted in (B7)3-(M2)2+ and (B8)2-(M2)2+ complexes with double (σ + π) aromatic boron wheels and a single bond for the metallic dimer. Above all, the computed rotational barriers of the M-M fragment with respect to the boron disk and molecular dynamics simulations indicate a virtually barrierless spin, resembling a magnetic stirrer on a baseplate.


Response of protein synthesis in human skeletal muscle to insulin: an investigation with L-[2H5]phenylalanine.
The role of insulin in the regulation of muscle protein synthesis in adult humans has been investigated with intravenous infusion of insulin at levels comparable with those observed after normal feeding. Glucose was also infused to maintain euglycemia. Muscle protein synthesis was measured in six healthy subjects before and during insulin and glucose infusion from the incorporation of L-[2H5]phenylalanine into the protein of vastus lateralis sampled by percutaneous biopsy. L-[2H5]phenylalanine was given as a single injection of a flooding amount (45 mg/kg). The relatively low levels of enrichment of phenylalanine in protein (0.005 atom%) were measured by modified gas chromatography-mass spectrometry and verified by comparison with incorporation of L-[2,6-3H]phenylalanine. Similarity of enrichment in tissue-free and plasma pools (flooding) and linear incorporation over the period of measurement were also verified. The fractional rate of muscle protein synthesis in the group of postabsorptive subjects was 1.65 +/- 0.11% (SE)/day. The rate was unaltered by insulin and glucose infusion, 1.66 +/- 0.16%/day.


Low concentrations of ethanol induce apoptosis in human intestinal cells.
Increased systemic levels of endotoxin have been detected in human alcoholics and are thought to be derived from the gut. Although a 'leaky gut' is considered to be a necessary factor for alcohol-induced endotoxemia followed by chronic liver injury, the effects of low concentrations of ethanol on intestinal epithelial cells have not been fully understood. The aim of this study was to evaluate intestinal epithelial cell death induced by acute, low concentrations of ethanol in an in vitro system. The human intestinal Caco-2 cell line was incubated with 0%, 5%, 10% ethanol for up to 3 h. Phosphatidylserine (PS) externalization, caspase-mediated cytokeratin 18 (CK18) cleavage, and DNA fragmentation were evaluated using flow cytometry. The caspase inhibitor zVAD-fmk was used to test the role of caspases in ethanol-induced cell death. Treatment with 5% and 10% ethanol for 3 h led to a gradual increase in PS externalization. Caspase-mediated CK18 was significantly enhanced as early as 1 h after 10% ethanol incubation, while DNA fragmentation was detected from 2 h onwards. Not only caspase activation but also both PS externalization and DNA fragmentation were completely prevented by pretreatment with the caspase inhibitor. Apoptotic cell death in confluent Caco-2 cells was induced by acute and low concentrations of ethanol. These results suggest that clinically achievable doses of ethanol impair intestinal barrier function by induction of apoptosis in intestinal epithelial cells. This impairment of the barrier function would allow endotoxin to enter the circulation and evoke hepatic inflammation.


Dissociation of gp120 from HIV-1 virions induced by soluble CD4.
The CD4 antigen is the high affinity cellular receptor for the human immunodeficiency virus type-1 (HIV-1). Binding of recombinant soluble CD4 (sCD4) or the purified V1 domain of sCD4 to the surface glycoprotein gp120 on virions resulted in rapid dissociation of gp120 from its complex with the transmembrane glycoprotein gp41. This may represent the initial stage in virus-cell and cell-cell fusion. Shedding of gp120 from virions induced by sCD4 may also contribute to the mechanism by which these soluble receptor molecules neutralize HIV-1.


Genome mapping of Clostridium perfringens strains with I-CeuI shows many virulence genes to be plasmid-borne.
The intron-encoded endonuclease I-CeuI from Chlamydomonas eugametos was shown to cleave the circular chromosomes of all Clostridium perfringens strains examined at single sites in the rRNA operons, thereby generating ten fragments suitable for the rapid mapping of virulence genes by pulsed-field gel electrophoresis (PFGE). This method easily distinguishes between plasmid and chromosomal localisations, as I-CeuI only cuts chromosomal DNA. Using this approach, the genes for three of the four typing toxins, beta, epsilon, and tau, in addition to the enterotoxin and lambda-toxin genes, were shown to be plasmid-borne. In a minority of strains, associated with food poisoning, where the enterotoxin toxin gene was located on the chromosome, genes for two of the minor toxins, theta and mu, were missing.


Retinal Configuration of ppR Intermediates Revealed by Photoirradiation Solid-State NMR and DFT.
Pharanois phoborhodopsin (ppR) from Natronomonas pharaonis is a transmembrane photoreceptor protein involved in negative phototaxis. Structural changes in ppR triggered by photoisomerization of the retinal chromophore are transmitted to its cognate transducer protein (pHtrII) through a cyclic photoreaction pathway involving several photointermediates. This pathway is called the photocycle. It is important to understand the detailed configurational changes of retinal during the photocycle. We previously observed one of the photointermediates (M-intermediates) by in situ photoirradiation solid-state NMR experiments. In this study, we further observed the 13C cross-polarization magic-angle-spinning NMR signals of late photointermediates such as O- and N'-intermediates by illumination with green light (520 nm). Under blue-light (365 nm) irradiation of the M-intermediates, 13C cross-polarization magic-angle-spinning NMR signals of 14- and 20-13C-labeled retinal in the O-intermediate appeared at 115.4 and 16.4 ppm and were assigned to the 13-trans, 15-syn configuration. The signals caused by the N'-intermediate appeared at 115.4 and 23.9 ppm and were assigned to the 13-cis configuration, and they were in an equilibrium state with the O-intermediate during thermal decay of the M-intermediates at -60°C. Thus, photoirradiation NMR studies revealed the photoreaction pathways from the M- to O-intermediates and the equilibrium state between the N'- and O-intermediate. Further, we evaluated the detailed retinal configurations in the O- and N'-intermediates by performing a density functional theory chemical shift calculation. The results showed that the N'-intermediate has a 63° twisted retinal state due to the 13-cis configuration. The retinal configurations of the O- and N'-intermediates were determined to be 13-trans, 15-syn, and 13-cis, respectively, based on the chemical shift values of [20-13C] and [14-13C] retinal obtained by photoirradiation solid-state NMR and density functional theory calculation.


Interpersonal violence in adolescence: ecological correlates of self-reported perpetration.
Although growing attention is being paid to the problem of teen dating violence, to date less is known about perpetrators of victimization. The current article used a subset of 980 adolescents aged 11 to 19 who were surveyed as part of a statewide community service coordinated through Cooperative Extension to survey all youth in target communities about risky health behaviors. The current article examined correlates of perpetration of either physical dating violence or sexual abuse across all levels of the ecological model (individual, family, and community factors). At the bivariate level, individual factors including substance use and low social responsibility, family factors including divorce, low parental monitoring, and low social support, and community variables such as low school attachment and neighborhood monitoring were associated with self-reported perpetration. At the multivariate level, gender and history of victimization were most significant in explaining variance in perpetration.


Novel insight into the genetic context of the cadAB genes from a 4-chloro-2-methylphenoxyacetic acid-degrading Sphingomonas.
The 2-methyl-4-chlorophenoxyacetic (MCPA) acid-degrader Sphingomonas sp. ERG5 has recently been isolated from MCPA-degrading bacterial communities. Using Illumina-sequencing, the 5.7 Mb genome of this isolate was sequenced in this study, revealing the 138 kbp plasmid pCADAB1 harboring the 32.5 kbp composite transposon Tn6228 which contains genes encoding proteins for the removal of 2,4-dichlorophenoxyacetic acid (2,4-D) and MCPA, as well as the regulation of this pathway. Transposon Tn6228 was confirmed by PCR to be situated on the plasmid and also exist in a circular intermediate state - typical of IS3 elements. The canonical tfdAα-gene of group III 2,4-D degraders, encoding the first step in degradation of 2,4-D and related compounds, was not present in the chromosomal contigs. However, the alternative cadAB genes, also providing the initial degradation step, were found in Tn6228, along with the 2,4-D-degradation-associated genes tfdBCDEFKR and cadR. Putative reductase and ferredoxin genes cadCD of Rieske non-heme iron oxygenases were also present in close proximity to cadAB, suggesting that these might have an unknown role in the initial degradation reaction. Parts of the composite transposon contain sequence displaying high similarity to previously analyzed 2,4-D degradation genes, suggesting rapid dissemination and high conservation of the chlorinated-phenoxyacetic acid (PAA)-degradation genotype among the sphingomonads.


Spatiotemporal Strategies for Joint Segmentation and Motion Tracking From Cardiac Image Sequences.
Although accurate and robust estimations of the deforming cardiac geometry and kinematics from cine tomographic medical image sequences remain a technical challenge, they have significant clinical value. Traditionally, boundary or volumetric segmentation and motion estimation problems are considered as two sequential steps, even though the order of these processes can be different. In this paper, we present an integrated, spatiotemporal strategy for the simultaneous joint recovery of these two ill-posed problems. We use a mesh-free Galerkin formulation as the representation and computation platform, and adopt iterative procedures to solve the governing equations. Specifically, for each nodal point, the external driving forces are individually constructed through the integration of data-driven edginess measures, prior spatial distributions of myocardial tissues, temporal coherence of image-derived salient features, imaging/image-derived Eulerian velocity information, and cyclic motion model of myocardial behavior. The proposed strategy is accurate and very promising application results are shown from synthetic data, magnetic resonance (MR) phase contrast, tagging image sequences, and gradient echo cine MR image sequences.


Adsorption geometry, molecular interaction, and charge transfer of triphenylamine-based dye on rutile TiO2(110).
The fast development of new organic sensitizers leads to the need for a better understanding of the complexity and significance of their adsorption processes on TiO(2) surfaces. We have investigated a prototype of the triphenylamine-cyanoacrylic acid (donor-acceptor) on rutile TiO(2) (110) surface with special attention on the monolayer region. This molecule belongs to the type of dye, some of which so far has delivered the record efficiency of 10%-10.3% for pure organic sensitizers [W. Zeng, Y. Cao, Y. Bai, Y. Wang, Y. Shi, M. Zhang, F. Wang, C. Pan, and P. Wang, Chem. Mater. 22, 1915 (2010)]. The molecular configuration of this dye on the TiO(2) surface was found to vary with coverage and adopt gradually an upright geometry, as determined from near edge x-ray absorption fine structure spectroscopy. Due to the molecular interaction within the increasingly dense packed layer, the molecular electronic structure changes systematically: all energy levels shift to higher binding energies, as shown by photoelectron spectroscopy. Furthermore, the investigation of charge delocalization within the molecule was carried out by means of resonant photoelectron spectroscopy. A fast delocalization (∼1.8 fs) occurs at the donor part while a competing process between delocalization and localization takes place at the acceptor part. This depicts the "push-pull" concept in donor-acceptor molecular system in time scale.


Selenium-containing tRNA(Glu) and tRNA(Lys) from Escherichia coli: purification, codon specificity and translational activity.
In response to low (approximately 1 microM) levels of selenium, Escherichia coli synthesizes tRNA(Glu) and tRNA(Lys) species that contain 5-methylaminomethyl-2-selenouridine (mnm5Se2U) instead of 5-methylaminomethyl-2-thiouridine (mnm5S2U). Purified glutamate- and lysine-accepting tRNAs containing either mnm5Se2U (tRNA(SeGlu), tRNA(SeLys] or mnm5S2U (tRNA(SGlu), tRNA(SLys] were prepared by RPC-5 reversed-phase chromatography, affinity chromatography using anti-AMP antibodies and DEAE-5PW ion-exchange HPLC. Since mnm5Se2U, like mnm5S2U, appears to occupy the wobble position of the anticodon, the recognition of glutamate codons (GAA and GAG) and lysine codons (AAA and AAG) was studied. While tRNA(SGlu) greatly preferred GAA over GAG, tRNA(SeGlu) showed less preference. Similarly, tRNA(SGlu) preferred AAA over AAG, while tRNA(SeLys) did not. In a wheat germ extract--rabbit globin mRNA translation system, incorporation of lysine and glutamate into protein was generally greater when added as aminoacylated tRNA(Se) than as aminoacylated tRNA(S). In globin mRNA the glutamate and lysine codons GAG and AAG are more numerous than GAA and AAA, thus a more efficient translation of globin message with tRNA(Se) might be expected because of facilitated recognition of codons ending in G.


Timing is everything: GTPase regulation in phototransduction.
As the molecular mechanisms of vertebrate phototransduction became increasingly clear in the 1980s, a persistent problem was the discrepancy between the slow GTP hydrolysis catalyzed by the phototransduction G protein, transducin, and the much more rapid physiological recovery of photoreceptor cells from light stimuli. Beginning with a report published in 1989, a series of studies revealed that transducin GTPase activity could approach the rate needed to explain physiological recovery kinetics in the presence of one or more factors present in rod outer segment membranes. One by one, these factors were identified, beginning with PDEγ, the inhibitory subunit of the cGMP phosphodiesterase activated by transducin. There followed the discovery of the crucial role played by the regulator of G protein signaling, RGS9, a member of a ubiquitous family of GTPase-accelerating proteins, or GAPs, for heterotrimeric G proteins. Soon after, the G protein β isoform Gβ5 was identified as an obligate partner subunit, followed by the discovery or R9AP, a transmembrane protein that anchors the RGS9 GAP complex to the disk membrane, and is essential for the localization, stability, and activity of this complex in vivo. The physiological importance of all of the members of this complex was made clear first by knockout mouse models, and then by the discovery of a human visual defect, bradyopsia, caused by an inherited deficiency in one of the GAP components. Further insights have been gained by high-resolution crystal structures of subcomplexes, and by extensive mechanistic studies both in vitro and in animal models.


Epigenetic control of cardiovascular health by nutritional polyphenols involves multiple chromatin-modifying writer-reader-eraser proteins.
Nowadays, epigenetic mechanisms involving DNA methylation, histone modifications and microRNA regulation emerge as important players in cardiovascular disease (CVD). Epigenetics may provide the missing link between environment, genome and disease phenotype and be responsible for the strong interindividual variation in disease risk factors underlying CVD. Daily diet is known to have a major influence on both the development and the prevention of CVD. Interestingly, the dietary lifestyle of our (grand)parents and of us contributes to CVD risk by metabolic (re)programming of our epigenome in utero, after birth or during life. In contrast to genetic mutations, the plasticity of CVD related epigenetic changes makes them attractive candidates for nutritional prevention or pharmacological intervention. Although a growing number of epidemiologic studies have shown a link between the ingestion of nutritional polyphenols and cardiovascular health benefits, potential involvement of epigenetic mechanisms has been underexplored. In this review, we will give an overview of epigenetic alterations in atherosclerosis, with the focus on DNA and histone modifications by chromatin-modifying proteins. Finally, we illustrate that cocoa flavanols and other classes of dietary molecules may promote cardiovascular health by targeting multiple classes of chromatin writer-reader-eraser proteins related to histone acetylation-methylation and DNA methylation.


Imaging Calcium Dynamics in Subpopulations of Mouse Pancreatic Islet Cells.
Pancreatic islet hormones regulate blood glucose homeostasis. Changes in blood glucose induce oscillations of cytosolic calcium in pancreatic islet cells that trigger secretion of three main hormones: insulin (from β-cells), glucagon (α-cells) and somatostatin (δ-cells). β-Cells, which make up the majority of islet cells and are electrically coupled to each other, respond to the glucose stimulus as one single entity. The excitability of the minor subpopulations, α-cells and δ-cells (making up around 20% (30%) and 4% (10%) of the total rodent1 (human2) islet cell numbers, respectively) is less predictable and is therefore of special interest. Calcium sensors are delivered into the peripheral layer of cells within the isolated islet. The islet or a group of islets is then immobilized and imaged using a fluorescence microscope. The choice of the imaging mode is between higher throughput (wide-field) and better spatial resolution (confocal). Conventionally, laser scanning confocal microscopy is used for imaging tissue, as it provides the best separation of the signal between the neighboring cells. A wide-field system can be utilized too, if the contaminating signal from the dominating population of β-cells is minimized. Once calcium dynamics in response to specific stimuli have been recorded, data are expressed in numerical form as fluorescence intensity vs. time, normalized to the initial fluorescence and baseline-corrected, to remove the effects linked to bleaching of the fluorophore. Changes in the spike frequency or partial area under the curve (pAUC) are computed vs. time, to quantify the observed effects. pAUC is more sensitive and quite robust whereas spiking frequency provides more information on the mechanism of calcium increase. Minor cell subpopulations can be identified using functional responses to marker compounds, such as adrenaline and ghrelin, that induce changes in cytosolic calcium in a specific populations of islet cells.


Treatment of acne in children.
Acne is a common skin condition in adolescents. It is not uncommon in childhood and it persists into adulthood. A broad range of acne treatments are available and have been shown to be safe and effective in adolescents and adults. However, there is limited literature regarding acne treatment in childhood and its available therapeutic options. It seems reasonable to extrapolate findings of the various studies reported on treatment of acne in the adolescent and adult age group, with the exclusion of the use of tetracycline derivatives. As clinicians, we must be more familiar with the clinical presentation of acne and available treatment options in our younger patients. Early recognition of acne with prompt and appropriate initiation of therapy in childhood will help prevent severe scarring in children.


Dynamic phenotypes of degenerative myxomatous mitral valve disease: quantitative 3-dimensional echocardiographic study.
Fibro-elastic deficiency (FED) and diffuse myxomatous degeneration (DMD) are phenotypes of degenerative mitral valve disease defined morphologically. Whether physiological differences in annular and valvular dynamics exist between these phenotypes remains unknown. We performed triple quantitation of cardiac remodeling and of mitral regurgitation severity and of annular and valvular dimensions by real-time 3-dimensional-transesophageal-echocardiography. Forty-nine patients with degenerative mitral valve disease classified as FED (n=31) and DMD (n=18) by surgical observation showed no difference in age (65±10 versus 59±13; P=0.5), body surface area (2.0±0.2 versus 2.0±0.2 m(2); P=0.5), left ventricular and atrial dimensions (all P>0.55), and mitral regurgitation regurgitant orifice (P=0.62). On average, annular dimensions were larger in DMD versus FED, but height was similar resulting in lower saddle shape. Dynamically, annular DMD versus FED display poorer contraction and saddle-shape accentuation in early systole and abnormal enlargement, particularly intercommissural, in late-systole (all P<0.05). Valvular dynamics showed stable valvular area in systole in FED versus considerable systolic increased area in DMD (P<0.001). Prolapse height and volume increased little throughout systole in FED versus marked increase in DMD (P<0.001). Our novel observations show that FED and DMD, although both labeled myxomatous, display considerable physiological phenotypic differences. In DMD, the annular increased size and profoundly abnormal dynamics demonstrate DMD-specific annular degeneration compared with the enlarged but relatively normal FED annulus. DMD does not incur more severe mitral regurgitation, despite larger prolapse and valve redundancy, underscoring potential compensatory role of tissue redundancy of DMD (or aggravating role of tissue paucity of FED) on mitral regurgitation severity.


The influence of family-supportive supervisor training on employee job performance and attitudes: An organizational work-family intervention.
Training supervisors to increase their family-supportive supervisor behaviors (FSSB) has demonstrated significant benefits for employee physical health, job satisfaction, and turnover intentions among employees with high levels of family-to-work conflict in prior research in a grocery store context. We replicate and extend these results in a health care setting with additional important employee outcomes (i.e., employee engagement, organizational commitment, and supervisor ratings of job performance), and consider the role of the 4 dimensions underlying the FSSB. Using a quasi-experimental, pretest-posttest design, 143 health care employees completed surveys at 2 time periods approximately 10 months apart, along with their supervisors who provided ratings of employees' job performance. Between these surveys, we offered their supervisors FSSB training; 86 (71%) of these supervisors participated. Results demonstrated significant and beneficial indirect effects of FSSB training on changes in employee job performance, organizational commitment, engagement, job satisfaction, and turnover intentions through changes in employee perceptions of their supervisor's overall FSSBs. Further analyses suggest that these indirect effects are due primarily to changes in the creative work-family management dimension of FSSB. (PsycINFO Database Record


Stability of alcohol use and teen dating violence for female youth: A latent transition analysis.
Alcohol use is one of the most widely accepted and studied risk factors for teen dating violence (TDV). Too little research has explored longitudinally if it is true that an adolescent's alcohol use and TDV involvement simultaneously occur. In the current study, we examined whether there were latent status based on past-year TDV and alcohol use and whether female adolescents changed their statuses of TDV and alcohol use over time. The sample consisted of 583 female youths in seven public high schools in Texas. Three waves of longitudinal data collected from 2011 to 2013 were utilised in this study. Participants completed self-report assessments of alcohol use (past-year alcohol use, number of drinks in the past month and episodic heavy drinking within the past month) and psychological and physical TDV victimisation and perpetration. Latent transition analysis was used to examine if the latent status based on TDV and alcohol use changed over time. Five separate latent statuses were identified: (i) no violence, no alcohol; (ii) alcohol; (iii) psychological violence, no alcohol; (iv) psychological violence, alcohol; and (v) physical and psychological violence, alcohol. Latent transition analysis indicated that adolescents generally remained in the same subgroup across time. This study provides evidence on the co-occurrence of alcohol use and teen dating violence, and whether teens' status based on dating violence and alcohol use are stable over time. Findings from the current study highlight the importance of targeting both TDV and substance use in intervention and prevention programs. [Choi HJ, Elmquist J, Shorey RC, Rothman EF, Stuart GL,Temple JR. Stability of alcohol use and teen dating violence for female youth: Alatent transition analysis. Drug Alcohol Rev 2017;36:80-87].


Agency and Anxiety: Delusions of Control and Loss of Control in Schizophrenia and Agoraphobia.
We review the distinction between sense of agency and sense of ownership, and then explore these concepts, and their reflective attributions, in schizophrenic symptoms and agoraphobia. We show how the underlying dynamics of these experiences are different across these disorders. We argue that these concepts are complex and cannot be reduced to neural mechanisms, but involve embodied and situated processes that include the physical and social environments. We conclude by arguing that the subjective and intersubjective dimensions of agency and ownership cannot be considered in isolation from one another, but instead form an interdependent pairing.


Mechanism of action of methyldopa in the rat. Role of 3-O-methylated metabolites.
We studied the effect of 3-O-methyl-methyldopa (OMMD), the 3-O-methylated metabolite of the antihypertensive drug methyldopa (alpha-methyldopa, AMD), on blood pressure in the spontaneously hypertensive rat. OMMD lowered blood pressure in a dose-related manner when given orally or intraperitoneally. Its action lasted longer than that of AMD, and daily oral administration produced a cumulative fall in blood pressure. Oral and intraperitoneal OMMD produced similar reductions of blood pressure and similar tissue OMMD levels. After intraperitoneal injection of different doses, levels of OMMD measured in brain, spinal cord, and plasma correlated with the magnitude of the antihypertensive effect. No AMD was detected in tissues after either route of administration, which suggests that the antihypertensive effect was not based on demethylation of OMMD to AMD. Peripheral inhibition of the enzyme, aromatic amino acid decarboxylase (AAAD), failed to suppress OMMD's effect on blood pressure; in contrast, central inhibition of AAAD did decrease OMMD's antihypertensive effect. These observations suggest that 3-O-methylated metabolites may participate in the antihypertensive effect of AMD.


Astragaloside IV Supplementation Promotes A Neuroprotective Effect in Experimental Models of Neurological Disorders: A Systematic Review.
Neurological disorders constitute a growing worldwide concern due to the progressive aging of the population and the risky behavior they represent. Herbal medicines have scientific relevance in the treatment of these pathologies. One of these substances, Astragaloside IV (AS-IV), is the main active compound present in the root of Astragalus membranaceus (Fisch.) Bge, a Chinese medicinal herb with neuroprotective properties. In the present study we performed a systematic review that sought to comprehend the neuroprotective effect presented by AS-IV in experimental models of neurological disorders. This study is a systematic review, where an electronic search in United States National Library of Medicine (PubMed), Science Direct, Cochrane Library, Scientific Electronic Library Online (SciELO), Scopus, Web of Science, Medline via Proquest and Periodicos Capes databases covering the years between 2007 and 2017, using "Astragaloside IV" and "Neurodegenerative diseases"; "Astragaloside IV" and " Neurological disorders" as reference terms was made. A total of 16 articles were identified, in which the efficacy of AS-IV was described in experimental models of Parkinson's disease, Alzheimer's disease, cerebral ischemia and autoimmune encephalomyelitis, by improving motor deficits and/or neurochemical activity, especially antioxidant systems, reducing inflammation and oxidative stress. The findings of the present study indicate that the administration of AS-IV can improve behavioral and neurochemical deficits largely due to its antioxidant, antiapoptotic and antiinflammatory properties, emerging as an alternative therapeutic approach for the treatment of neurological disorders.


Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle.
Pharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challenge drug over a short time scale, and functional imaging to rapidly provide quantitative estimates of drug sensitivity including EC 50 (the concentration of drug that produces half the maximum possible effect). We first test the method with simulated data, assuming a typical sigmoidal dose-response curve and assuming imperfect imaging that includes artifactual baseline signal drift and random error. With these few assumptions, rapid quantitative pharmacodynamic imaging reliably estimates EC 50 from the simulated data, except when noise overwhelms the drug effect or when the effect occurs only at high doses. In preliminary fMRI studies of primate brain using a dopamine agonist, the observed noise level is modest compared with observed drug effects, and a quantitative EC 50 can be obtained from some regional time-signal curves. Taken together, these results suggest that research and clinical applications for rapid quantitative pharmacodynamic imaging are realistic.


Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection.
Palivizumab was licensed in June 1998 by the Food and Drug Administration for the reduction of serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at increased risk of severe disease. Since that time, the American Academy of Pediatrics has updated its guidance for the use of palivizumab 4 times as additional data became available to provide a better understanding of infants and young children at greatest risk of hospitalization attributable to RSV infection. The updated recommendations in this policy statement reflect new information regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. This policy statement updates and replaces the recommendations found in the 2012 Red Book.


Naltrexone Restores Impaired Transient Receptor Potential Melastatin 3 Ion Channel Function in Natural Killer Cells From Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a seriously long-term and debilitating illness of unknown cause hallmarked by chronic pain and fatigue, memory and concentration impairment, and inflammation. ME/CFS hypothesis involves impaired Transient receptor potential melastatin 3 (TRPM3) ion channel function, affecting calcium signaling and Natural killer (NK) cell functions. Currently, substances called opioids, agonists of mu (μ)-opioid receptors (μOR), are the strongest painkillers clinically available for people suffering from strong or long-lasting pain characteristic of ME/CFS. μOR have been reported to specifically inhibit TRPM3 and to be expressed in immune cells where they play an immunomodulatory and immunosuppressive role. Naltrexone hydrochloride (NTX) acts as an antagonist to the μOR thus negating the inhibitory function of this opioid receptor on TRPM3. Therefore, understanding the mechanism of action for NTX in regulating and modulating TRPM3 channel function in NK cells will provide important information for the development of effective therapeutic interventions for ME/CFS. Whole-cell patch-clamp technique was used to measure TRPM3 activity in Interleukin-2 (IL-2) stimulated and NTX-treated NK cells for 24 h on eight ME/CFS patients and 8 age- and sex-matched healthy controls, after modulation with a TRPM3-agonist, pregnenolone sulfate (PregS), NTX and a TRPM3-antagonist, ononetin. We confirmed impaired TRPM3 function in ME/CFS patients through electrophysiological investigations in IL-2 stimulated NK cells after modulation with PregS and ononetin. Importantly, TRPM3 channel activity was restored in IL-2 stimulated NK cells isolated from ME/CFS patients after incubation for 24 h with NTX. Moreover, we demonstrated that NTX does not act as an agonist by directly coupling on the TRPM3 ion channel gating. The opioid antagonist NTX has the potential to negate the inhibitory function of opioid receptors on TRPM3 in NK cells from ME/CFS patients, resulting in calcium signals remodeling, which will in turn affect cell functions, supporting the hypothesis that NTX may have potential for use as a treatment for ME/CFS. Our results demonstrate, for the first time, and based on novel patch clamp electrophysiology, potential pharmaco-therapeutic interventions in ME/CFS.


β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells.
Complement system and dendritic cells (DCs) form - beside neutrophils and macrophages - the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1tetOnrep under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1tetOn mutant a good model to study immune-modulatory actions of these drugs. We now demonstrate herein, that complement was activated to significantly higher levels by the fks1-deficient strain compared to its respective wild type. This enhanced covalent linking of complement fragments to the A. fumigatus fks1tetOnrep mutant further resulted in enhanced DC binding and internalization of the fungus. Additionally, we found that fks1tetOnrep induced a Th1-/Th17-polarizing cytokine profile program in DCs. The effect was essentially dependent on massive galactomannan shedding, since blocking of DC-SIGN significantly reduced the fks1tetOnrep-mediated induction of an inflammatory cytokine profile.Our data demonstrate that lack of ß-1,3-glucan, also found under echinocandin therapy, results in improved recognition of Aspergillus fumigatus by complement and DCs and therefore not only directly affects the fungus by its fungistatic actions, but also is likely to exert indirect antifungal mechanisms by strengthening innate host immune mechanisms.Abbreviations: C: complement; CR:complement receptor; DC: dendritic cell; iDC: immature dendritic cell; DC-SIGN: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; ERK: extracellular signal-regulated kinases; JNK : c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinase; NHS: normal human serum; PRR: pattern recognition receptor; Th :T helper; TLR :Toll-like receptor; WT: wild type.


Elongated Hypocotyl 5-Homolog (HYH) Negatively Regulates Expression of the Ambient Temperature-Responsive MicroRNA Gene MIR169.
Arabidopsis microRNA169 (miR169) is an ambient temperature-responsive microRNA that plays an important role in stress responses and the floral transition. However, the transcription factors that regulate the expression of MIR169 have remained unknown. In this study, we show that Elongated Hypocotyl 5-Homolog (HYH) directly binds to the promoter of MIR169a and negatively regulates its expression. Absolute quantification identified MIR169a as the major locus producing miR169. GUS reporter assays revealed that the deletion of a 498-bp fragment (-1,505 to -1,007, relative to the major transcriptional start site) of MIR169a abolished its ambient temperature-responsive expression. DNA-affinity chromatography followed by liquid chromatography-mass spectrometry analysis identified transcription factor HYH as a trans-acting factor that binds to the 498-bp promoter fragment of pri-miR169a. Electrophoretic mobility shift assays and chromatin immunoprecipitation-quantitative PCR demonstrated that the HYH.2 protein, a predominant isoform of HYH, directly associated with a G-box-like motif in the 498-bp fragment of pri-miR169a. Higher enrichment of HYH.2 protein on the promoter region of MIR169a was seen at 23°C, consistent with the presence of more HYH.2 protein in the cell at the temperature. Transcript levels of pri-miR169a increased in hyh mutants and decreased in transgenic plants overexpressing HYH. Consistent with the negative regulation of MIR169a by HYH, the diurnal levels of HYH mRNA and pri-miR169a showed opposite patterns. Taken together, our results suggest that HYH is a transcription factor that binds to a G-box-like motif in the MIR169a promoter and negatively regulates ambient temperature-responsive expression of MIR169a at higher temperatures in Arabidopsis.


Right-hemispheric dominance for visual remapping in humans.
We review evidence showing a right-hemispheric dominance for visuo-spatial processing and representation in humans. Accordingly, visual disorganization symptoms (intuitively related to remapping impairments) are observed in both neglect and constructional apraxia. More specifically, we review findings from the intervening saccade paradigm in humans--and present additional original data--which suggest a specific role of the asymmetrical network at the temporo-parietal junction (TPJ) in the right hemisphere in visual remapping: following damage to the right dorsal posterior parietal cortex (PPC) as well as part of the corpus callosum connecting the PPC to the frontal lobes, patient OK in a double-step saccadic task exhibited an impairment when the second saccade had to be directed rightward. This singular and lateralized deficit cannot result solely from the patient's cortical lesion and, therefore, we propose that it is due to his callosal lesion that may specifically interrupt the interhemispheric transfer of information necessary to execute accurate rightward saccades towards a remapped target location. This suggests a specialized right-hemispheric network for visuo-spatial remapping that subsequently transfers target location information to downstream planning regions, which are symmetrically organized.


Shared characteristics underpinning C4 leaf maturation derived from analysis of multiple C3 and C4 species of Flaveria.
Most terrestrial plants use C3 photosynthesis to fix carbon. In multiple plant lineages a modified system known as C4 photosynthesis has evolved. To better understand the molecular patterns associated with induction of C4 photosynthesis, the genus Flaveria that contains C3 and C4 species was used. A base to tip maturation gradient of leaf anatomy was defined, and RNA sequencing was undertaken along this gradient for two C3 and two C4 Flaveria species. Key C4 traits including vein density, mesophyll and bundle sheath cross-sectional area, chloroplast ultrastructure, and abundance of transcripts encoding proteins of C4 photosynthesis were quantified. Candidate genes underlying each of these C4 characteristics were identified. Principal components analysis indicated that leaf maturation and the photosynthetic pathway were responsible for the greatest amount of variation in transcript abundance. Photosynthesis genes were over-represented for a prolonged period in the C4 species. Through comparison with publicly available data sets, we identify a small number of transcriptional regulators that have been up-regulated in diverse C4 species. The analysis identifies similar patterns of expression in independent C4 lineages and so indicates that the complex C4 pathway is associated with parallel as well as convergent evolution.


Mitral valvular cyst mimicking a solid mass: misdiagnosis with imaging modalities.
This report describes a mitral valvular cyst mimicking a solid mass in an 80-year-old patient. The diagnosis was based on histopathological evaluation of the resected material. This report emphasizes the possibility of misdiagnosis by echocardiographic and other imaging modalities of a mitral valvular mass in a patient without any clinical signs and symptoms.


Compartmentalization and regulation of mitochondrial function by methionine sulfoxide reductases in yeast.
Elevated levels of reactive oxygen species can damage proteins. Sulfur-containing amino acid residues, cysteine and methionine, are particularly susceptible to such damage. Various enzymes evolved to protect proteins or repair oxidized residues, including methionine sulfoxide reductases MsrA and MsrB, which reduce methionine (S)-sulfoxide (Met-SO) and methionine (R)-sulfoxide (Met-RO) residues, respectively, back to methionine. Here, we show that MsrA and MsrB are involved in the regulation of mitochondrial function. Saccharomyces cerevisiae mutant cells lacking MsrA, MsrB, or both proteins had normal levels of mitochondria but lower levels of cytochrome c and fewer respiration-competent mitochondria. The growth of single MsrA or MsrB mutants on respiratory carbon sources was inhibited, and that of the double mutant was severely compromised, indicating impairment of mitochondrial function. Although MsrA and MsrB are thought to have similar roles in oxidative protein repair each targeting a diastereomer of methionine sulfoxide, their deletion resulted in different phenotypes. GFP fusions of MsrA and MsrB showed different localization patterns and primarily localized to cytoplasm and mitochondria, respectively. This finding agreed with compartment-specific enrichment of MsrA and MsrB activities. These results show that oxidative stress contributes to mitochondrial dysfunction through oxidation of methionine residues in proteins located in different cellular compartments.


Genetic determinants of Potato virus Y required to overcome or trigger hypersensitive resistance to PVY strain group O controlled by the gene Ny in potato.
Potato virus Y (PVY) (genus Potyvirus) is the most economically damaging and widely distributed virus in potato. Spread of PVY in the field is controlled by growing resistant cultivars. The dominant potato gene Ny(tbr) for hypersensitive resistance (HR) controls ordinary PVY strains (PVY(O)) but is overcome by PVY(N) strains. Studies with infectious PVY chimeras and mutants indicated that the viral determinants necessary and sufficient to overcome Ny(tbr) reside within the helper component proteinase (HC-Pro) (residues 227 to 327). Specifically, eight residues and the modeled three-dimensional conformation of this HC-Pro region distinguish PVY(N) from PVY(O) strains. According to the model, the conserved IGN and CCCT motifs implicated in potyvirus replication and movement, respectively, are situated in a coiled structure and an α-helix, respectively, within this region in PVY(O); however, their locations are reversed in PVY(N). Two residues (R269 and K270) are crucial for the predicted PVY(O)-specific HC-Pro conformation. Two viral chimeras triggered Ny(tbr) and induced veinal necrosis in tobacco, which is novel for PVY. One chimera belonged to strain group PVY(E). Our results suggest a structure-function relationship in recognition of PVY(O) HC-Pro by Ny(tbr), reveal HC-Pro amino acid signatures specific to PVY(O) and PVY(N), and facilitate identification of PVY strains overcoming Ny(tbr).


Treating prediabetes with metformin: systematic review and meta-analysis.
To determine if the use of metformin in people with prediabetes (impaired glucose tolerance or impaired fasting glucose) would prevent or delay the onset of frank type 2 diabetes mellitus. MEDLINE was searched from January 1966 to the present, and articles meeting the selection criteria were hand searched. Randomized controlled trials that involved administration of metformin to delay or prevent type 2 diabetes in individuals with impaired glucose tolerance or impaired fasting glucose were included. Development of diabetes was a required outcome measure; follow-up time of at least 6 months was required. Three studies met these criteria. The 3 studies varied in ethnicity of the population studied, in the rates of conversion to diabetes from prediabetes, and in the dose of metformin used. In general the studies were well done, although 2 of the 3 did not do true intention-to-treat analyses. A sensitivity analysis was completed by converting all data to intention-to-treat data and assuming a worst-case scenario for the people who were lost to follow-up. Metformin decreases the rate of conversion from prediabetes to diabetes. This was true at higher dosage (850 mg twice daily) and lower dosage (250 mg twice or 3 times daily); in people of varied ethnicity; and even when a sensitivity analysis was applied to the data. The number needed to treat was between 7 and 14 for treatment over a 3-year period.


Selectivity control in the separation of aromatic amino acid enantiomers with sulphated beta-cyclodextrin.
Control of selectivity in the enantiomeric separation of three aromatic amino acids (phenylalanine, tyrosine and tryptophan) is demonstrated by electrokinetic capillary chromatography utilising temperature variations coupled with the use of sulphated-beta-cyclodextrin (s-beta-CD) as a pseudostationary phase. The concentration of s-beta-CD and temperature were used as experimental variables to control the observed selectivity. A double-coated capillary was used and proved very robust with reproducibility of migration times being <2.0% R.S.D. between runs and <2.6% on using a new capillary. The system was modelled successfully using an artificial neural network (ANN) comprising one input layer, two hidden layers and one output layer. The model accurately described the observed separations with a correlation coefficient of 0.999 being observed between predicted and observed migration times. Selectivity optimisation was achieved using the normalised resolution product and minimum resolution criteria, with both providing optima at different experimental conditions. The selectivity changes observed also allowed the estimation of electrolyte temperatures within the capillary at high operating currents (>100 microA). Using a 50 microm i.d. capillary and an electrolyte comprising 20 mM phosphate and 15 mM s-beta-CD, a temperature of 52 degrees C was calculated within the capillary at an applied voltage of +30 kV.


Lipopolysaccharide induces cyclooxygenase-2 in intestinal epithelium via a noncanonical p38 MAPK pathway.
Necrotizing enterocolitis (NEC), a severe intestinal inflammation in neonates, occurs following bacterial colonization of the gut. LPS-induced production of inflammatory factors in immature enterocytes may be a factor in NEC. Previously, we described LPS-induced p38 MAPK-dependent expression of cyclooxygenase-2 (COX-2) in rat IEC-6 cells. In this study, we examine COX-2 expression in newborn rat intestinal epithelium and further characterize the mechanisms of COX-2 regulation in enterocytes. Induction of NEC by formula feeding/hypoxia increased phospho-p38 and COX-2 levels in the intestinal mucosa. Celecoxib, a selective COX-2 inhibitor, exacerbated the disease, suggesting a protective role for COX-2. COX-2 was induced in the intestinal epithelium by LPS in vivo and ex vivo. The latter response was attenuated by the p38 inhibitor SB202190, but not by inhibitors of ERK, JNK, or NF-kappaB. In IEC-6 enterocytes, COX-2 was induced by the expression of MAPK kinase 3 EE (MKK3EE), a constitutive activator of p38, but not of activators of ERK or JNK pathways. However, neither MKK3/6 nor MKK4, the known p38 upstream kinases, were activated by LPS. Dominant-negative MKK3 or MKK4 or SB202190 failed to prevent LPS-induced, p38-activating phosphorylation, ruling out important roles of these kinases or p38 autophosphorylation. LPS increased COX-2 and activating phosphorylation of p38 with similar dose-response. Blockade of LPS-induced expression of COX-2-luciferase reporter and destabilization of COX-2 message by SB202190 indicate that p38 regulates COX-2 at transcription and mRNA stability levels. Our data indicate that p38-mediated expression of COX-2 proceeds through a novel upstream pathway and support the role of the neonate's enterocytes as bacterial sensors.


Indomethacin attenuates the cerebral blood flow response to hypotension in late-gestation fetal sheep.
Previous studies by us and others have demonstrated that PGE(2) and thromboxane (Tx) B(2) are produced in the fetal and neonatal brain during cerebral hypoperfusion. The present study was to test the hypotheses that indomethacin would alter the cerebral blood flow (CBF) response to reduced cerebral perfusion pressure in late-gestation fetal sheep by inhibiting the local prostanoid production. We studied eight chronically catheterized, sinoaortically denervated, 126- to 136-day gestation fetal sheep. The cyclooxygenase inhibitor indomethacin (0.2 mg/kg) or its vehicle phosphate buffer was injected intravenously 90 min before the start of a 10-min period of cerebral hypoperfusion produced by brachiocephalic artery occlusion (BCO). We found that BCO decreased fetal regional CBF (rCBF) by 65-79% in the phosphate buffer group and by 45-57% in the indomethacin-pretreated group. The decrease in fetal rCBF during BCO after indomethacin was 30-49% less than after phosphate buffer. Plasma PGE(2) and TxB(2) concentrations were significantly reduced by indomethacin treatment. BCO increased plasma ACTH and arginine vasopressin (AVP) concentrations; but these responses were not affected by indomethacin. These data suggested that endogenous prostanoid production is involved in the regulation of fetal CBF but, in the absence of intact baro- or chemoreflexes, not in the regulation of ACTH or AVP responses to BCO. We conclude that indomethacin has a beneficial effect on CBF during cerebral ischemia in late-gestation fetal sheep.


Determining expression of miRNAs that potentially regulate STAT5A and 5B in dasatinib-sensitive K562 cells.
In the era of tyrosine kinase inhibitors, resistance still constitutes a problem in chronic myeloid leukemia (CML) patients; thus, new pathway-specific inhibitors like miRNAs have become important in the treatment of refractory patients. There are no satisfying data regarding the miRNAs and anti-miRNA treatment targeting STAT5A and 5B. In this study, we first researched the effect of dasatinib on apoptosis in the CML cell line K562. The expressions of miRNAs possibly targeting both STAT5A and 5B were then determined. The down- and upregulation of the miRNAs were compared using the ΔΔCT method. At the last stage of the study, we used a new primer probe in order to validate the results. The level of hsa-miR-940 was decreased 4.4 times and the levels of hsa-miR-527 and hsa-miR-518a-5p were increased 12.1 and 8 times, respectively, in the dasatinib-treated group when compared to the control group. We detected similar results in the validation step. As a conclusion, we determined the expression profiles of miRNAs targeting STAT5A and 5B that had an important role in the pathogenesis of CML. The data obtained could lead to determining new therapeutic targets for CML patients.


Non-animal methodologies within biomedical research and toxicity testing.
Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues are used, non-animal models may generate faster, cheaper results, more reliably predictive for humans, whilst yielding greater insights into human biochemical processes. Greater commitment to their development and implementation is necessary, however, to efficiently meet the needs of high-throughput chemical testing programmes, important emerging testing needs, and the ongoing development of human clinical interventions.


Data-driven research and healthcare: public trust, data governance and the NHS.
It is widely acknowledged that trust plays an important role for the acceptability of data sharing practices in research and healthcare, and for the adoption of new health technologies such as AI. Yet there is reported distrust in this domain. Although in the UK, the NHS is one of the most trusted public institutions, public trust does not appear to accompany its data sharing practices for research and innovation, specifically with the private sector, that have been introduced in recent years. In this paper, we examine the question of, what is it about sharing NHS data for research and innovation with for-profit companies that challenges public trust? To address this question, we draw from political theory to provide an account of public trust that helps better understand the relationship between the public and the NHS within a democratic context, as well as, the kind of obligations and expectations that govern this relationship. Then we examine whether the way in which the NHS is managing patient data and its collaboration with the private sector fit under this trust-based relationship. We argue that the datafication of healthcare and the broader 'health and wealth' agenda adopted by consecutive UK governments represent a major shift in the institutional character of the NHS, which brings into question the meaning of public good the NHS is expected to provide, challenging public trust. We conclude by suggesting that to address the problem of public trust, a theoretical and empirical examination of the benefits but also the costs associated with this shift needs to take place, as well as an open conversation at public level to determine what values should be promoted by a public institution like the NHS.


Genetic Alterations in Anaplastic Thyroid Carcinoma.
Anaplastic thyroid cancer (ATC) is rare but fatal thyroid cancer responsible for majority of thyroid cancer related mortality. ATC may originate de novo or from preexisting differentiated thyroid cancer. Complex interaction between different gene mutation has been suggested to be the main causative factor for origin of ATC in both pathways. Mostly affected pathways are MAP kinase and PI3CA kinase. Hence, we decided to study the frequent alterations in both the pathways in ATC patients. Clinico-pathological data of 34 ATC patients were collected retrospectively and Formalin Fixed Paraffin Embedded (FFPE) blocks were taken out for genetic analysis. DNA and RANA were isolated from FFPE tissues. BRAF V600E mutations were screened by RFLP PCR method and confirmed by sequencing. RAS, PI3CA and p53 mutations were checked by sequencing. RET/PTC translocations were screened by Real Time PCR. A total of 34 patients were studied: Mean age 58.6+ 11.6 years with F:M- 1.8:1, 60% had history of goiter. Most common presenting symptom was rapidly growing thyroid mass followed by dyspnea, dysphasia and hoarseness of voice. Extent of disease was local, locoregional and metastatic in 32%, 35% and 33% respectively. 57.6% were euthyroid, 20.5 % were hyperthyroid while functional status were not available in 11.7%. FNAC was suggestive of ATC only in 52.9% cases. 15 (44%) were operated. BRAF V600E mutations were observed in 10/34 (29.4%). Interestingly, all three ATC patients with DTC components had previous history of goiter with rapid increase in size and BRAF V600E mutation, while BRAF was positive only in 7/31 (22.5%) of patients with no DTC component. Mean survival of 3.5 months in BRAF positive cases in comparison to 5.5 months in BRAF negative ATC. RAS mutations were found to be positive in 5.8%, and none had RET-PTC/PI3CA mutations. P53 mutation was positive in 7 patients. 3 patients presented with history of rapid increase in size of previous goiter while rest 4 patients presented with rapidly increasing thyroid swelling of 1 to 3 months. At presentation 2 patients has disease localized to thyroid, 4 has loco-regional disease and one patient presented with metastasis. 5 out of these 7 patients were operated (Total thyroidectomy:3, thyroidectomy with neck dissection:2). Mean survival was 4 months (1-6 months). BRAF V600E was the commonest mutation followed by p53 of the 5 genes tested and BRAF was more common in patients with previous history of longstanding goiter or differentiated thyroid cancer. This provides an indirect evidence of neoplastic transformation of PTC to ATC.


Spatio-temporal dynamics of adaptation in the human visual system: a high-density electrical mapping study.
When sensory inputs are presented serially, response amplitudes to stimulus repetitions generally decrease as a function of presentation rate, diminishing rapidly as inter-stimulus intervals (ISIs) fall below 1 s. This 'adaptation' is believed to represent mechanisms by which sensory systems reduce responsivity to consistent environmental inputs, freeing resources to respond to potentially more relevant inputs. While auditory adaptation functions have been relatively well characterized, considerably less is known about visual adaptation in humans. Here, high-density visual-evoked potentials (VEPs) were recorded while two paradigms were used to interrogate visual adaptation. The first presented stimulus pairs with varying ISIs, comparing VEP amplitude to the second stimulus with that of the first (paired-presentation). The second involved blocks of stimulation (N = 100) at various ISIs and comparison of VEP amplitude between blocks of differing ISIs (block-presentation). Robust VEP modulations were evident as a function of presentation rate in the block-paradigm, with strongest modulations in the 130-150 ms and 160-180 ms visual processing phases. In paired-presentations, with ISIs of just 200-300 ms, an enhancement of VEP was evident when comparing S2 with S1, with no significant effect of presentation rate. Importantly, in block-presentations, adaptation effects were statistically robust at the individual participant level. These data suggest that a more taxing block-presentation paradigm is better suited to engage visual adaptation mechanisms than a paired-presentation design. The increased sensitivity of the visual processing metric obtained in the block-paradigm has implications for the examination of visual processing deficits in clinical populations.


NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.


Sexual values and risky sexual behaviors among Latino youths.
Understanding Latino youths' sexual values is key to informing HIV prevention efforts. Few studies have examined associations between culturally based sexual values and behaviors among Latinos. A sample of 839 sexually active Latinos aged 16-22 residing in San Francisco were interviewed in 2003-2006. Multiple regression and multinomial logistic regression analyses were conducted to examine associations between sexual values and behaviors, while adjusting for language use (a proxy for acculturation) and other covariates. The importance attached to female virginity was negatively associated with the number of sexual partners women had had in their lifetime (odds ratio, 0.8) and in the past year (0.9), and was positively associated with women's nonuse of condoms, rather than consistent use, during the first month of their current relationships (1.8). For men, the importance of satisfying sexual needs increased with the numbers of lifetime and recent sexual partners (1.4 and 1.1, respectively), and with inconsistent condom use in the first month of their relationships (1.9). Comfort with sexual communication was positively associated with inconsistent use or nonuse of condoms in the last month of both men's and women's current relationships (2.0-2.2). For women, considering satisfaction of sexual needs important was associated with more sexual partners only among those who attached little value to female virginity. It is important to integrate themes of virginity and sexual desire into intervention curricula so youth can better understand how these sexual norms influence their developing sexual identities and behaviors.


Four decades of forest persistence, clearance and logging on Borneo.
The native forests of Borneo have been impacted by selective logging, fire, and conversion to plantations at unprecedented scales since industrial-scale extractive industries began in the early 1970s. There is no island-wide documentation of forest clearance or logging since the 1970s. This creates an information gap for conservation planning, especially with regard to selectively logged forests that maintain high conservation potential. Analysing LANDSAT images, we estimate that 75.7% (558,060 km2) of Borneo's area (737,188 km2) was forested around 1973. Based upon a forest cover map for 2010 derived using ALOS-PALSAR and visually reviewing LANDSAT images, we estimate that the 1973 forest area had declined by 168,493 km2 (30.2%) in 2010. The highest losses were recorded in Sabah and Kalimantan with 39.5% and 30.7% of their total forest area in 1973 becoming non-forest in 2010, and the lowest in Brunei and Sarawak (8.4%, and 23.1%). We estimate that the combined area planted in industrial oil palm and timber plantations in 2010 was 75,480 km2, representing 10% of Borneo. We mapped 271,819 km of primary logging roads that were created between 1973 and 2010. The greatest density of logging roads was found in Sarawak, at 0.89 km km-2, and the lowest density in Brunei, at 0.18 km km-2. Analyzing MODIS-based tree cover maps, we estimate that logging operated within 700 m of primary logging roads. Using this distance, we estimate that 266,257 km2 of 1973 forest cover has been logged. With 389,566 km2 (52.8%) of the island remaining forested, of which 209,649 km2 remains intact. There is still hope for biodiversity conservation in Borneo. Protecting logged forests from fire and conversion to plantations is an urgent priority for reducing rates of deforestation in Borneo.


Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C.
Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis. Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation. A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303). We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency. Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.


Primate immune responses to HIV-1 Env formulated in the saponin-based adjuvant AbISCO-100 in the presence or absence of TLR9 co-stimulation.
Protein-based vaccines require adjuvants to achieve optimal responses. Toll-like receptor (TLR) 9 agonists were previously shown to improve responses to protein-based vaccines, such as the Hepatitis B virus vaccine formulated in alum. Here, we used CpG-C together with the clinically relevant saponin-based adjuvant AbISCO-100/Matrix-M (AbISCO), to assess if TLR9 co-stimulation would quantitatively or qualitatively modulate HIV-1 envelope glycoprotein (Env)-specific B and T cell responses in rhesus macaques. The macaques were inoculated with soluble Env trimers in AbISCO, with or without the addition of CpG-C, using an interval similar to the Hepatitis B virus vaccine. Following a comprehensive evaluation of antigen-specific responses in multiple immune compartments, we show that the Env-specific circulating IgG, memory B cells and plasma cells displayed similar kinetics and magnitude in the presence or absence of CpG-C and that there was no apparent difference between the two groups in the elicited HIV-1 neutralizing antibody titers or antigen-specific CD4+ T cell responses. Importantly, the control of SHIV viremia was significantly improved in animals from both Env-immunized groups relative to adjuvant alone controls, demonstrating the potential of AbISCO to act as a stand-alone adjuvant for Env-based vaccines.


Melancholic symptoms as assessed by the Hamilton Depression Rating Scale and outcomes with and without electroconvulsive therapy on an in-patient mood disorders unit.
Rasmussen KG, Stevens SR, Kung S, Mohan A. Melancholic symptoms as assessed by the Hamilton Depression Rating Scale and outcomes with and without electroconvulsive therapy on an in-patient mood disorders unit. We investigated whether 24-item Hamilton Rating Scale for Depression (HamD24)-based melancholia ratings correlated with treatment outcome, with special focus on whether electroconvulsive therapy (ECT) was used in depressed patients treated on an in-patient mood disorders unit. We analysed the data on ECT- versus non-ECT-treated patients' outcomes relative to melancholia subscale scores. Two HamD24-based melancholia rating scale scores were computed for 201 depressed in-patients at admission and discharge. Baseline melancholia ratings were analysed to see if they correlated with improvement in total HamD24 scores. We also tested to see if the melancholia subscales followed unimodal or bimodal distributions. Melancholic symptoms as assessed by one of the HamD24-based subscales directly correlated with overall improvement. Although ECT treatment was associated with greater improvement than was noted in non-ECT-treated patients, severity of melancholia ratings did not affect this relationship. Finally, both melancholia subscale scores followed approximately unimodal distributions. HamD24-based methods to assess severity of melancholic symptoms have limited clinical utility on an in-patient mood disorders unit in general, and for predicting ECT response in particular. Furthermore, these methods do not seem to identify bimodal populations of depressed patients (i.e. melancholic vs. non-melancholic).


Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro.
We review the characteristics of osteoblast differentiation and bone matrix synthesis. Bone in air breathing vertebrates is a specialized tissue that developmentally replaces simpler solid tissues, usually cartilage. Bone is a living organ bounded by a layer of osteoblasts that, because of transport and compartmentalization requirements, produce bone matrix exclusively as an organized tight epithelium. With matrix growth, osteoblasts are reorganized and incorporated into the matrix as living cells, osteocytes, which communicate with each other and surface epithelium by cell processes within canaliculi in the matrix. The osteoblasts secrete the organic matrix, which are dense collagen layers that alternate parallel and orthogonal to the axis of stress loading. Into this matrix is deposited extremely dense hydroxyapatite-based mineral driven by both active and passive transport and pH control. As the matrix matures, hydroxyapatite microcrystals are organized into a sophisticated composite in the collagen layer by nucleation in the protein lattice. Recent studies on differentiating osteoblast precursors revealed a sophisticated proton export network driving mineralization, a gene expression program organized with the compartmentalization of the osteoblast epithelium that produces the mature bone matrix composite, despite varying serum calcium and phosphate. Key issues not well defined include how new osteoblasts are incorporated in the epithelial layer, replacing those incorporated in the accumulating matrix. Development of bone in vitro is the subject of numerous projects using various matrices and mesenchymal stem cell-derived preparations in bioreactors. These preparations reflect the structure of bone to variable extents, and include cells at many different stages of differentiation. Major challenges are production of bone matrix approaching the in vivo density and support for trabecular bone formation. In vitro differentiation is limited by the organization and density of osteoblasts and by endogenous and exogenous inhibitors.


Humoral immune response to a recombinant hemoplasma antigen in experimental 'Candidatus Mycoplasma turicensis' infection.
'Candidatus Mycoplasma turicensis' is a feline hemoplasma species that was isolated in a cat with hemolytic anemia. PCR has been widely used to investigate and diagnose 'Candidatus Mycoplasma turicensis' infection, but so far, little is known about the humoral immune response in infected cats. Recently, enzyme-linked immunosorbent assays (ELISA) were developed to monitor anti-feline hemoplasma antibodies. The aim of the present study was to investigate the humoral immune response in cats experimentally infected with 'Candidatus Mycoplasma turicensis' and to monitor the influence of the pre-administration of methylprednisolone and subsequent antibiotic treatment. Serum and plasma samples from 15 specified pathogen-free cats infected with 'Candidatus Mycoplasma turicensis' were analyzed by ELISA. Seroconversion was demonstrated in all cats, and the antibodies remained detectable until the end of the study (up to 100 weeks post-exposure). In some cats, the ELISA seemed more sensitive and better able to demonstrate exposure to 'Candidatus Mycoplasma turicensis' than PCR. The peak antibody level occurred after the peak of the bacterial blood loads. The methylprednisolone administrations were associated with increased antibody levels, while antibiotic treatment, particularly with doxycycline, resulted in a decrease in antibody levels. Additionally, preliminary data indicated that three of four seropositive cats were protected from bacteremia after a subsequent challenge. In conclusion, the ELISA was found to be a useful tool to investigate the humoral immune response in hemoplasma-infected cats and a desirable addition to PCR to study the pathogenesis of hemoplasma infections.


Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants.
Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants and increases the risk of adverse outcomes. Indomethacin has been the standard treatment to close a PDA but is associated with renal, gastrointestinal and cerebral side-effects. Ibuprofen has less effect on blood flow velocity to important organs. To determine the effectiveness and safety of prophylactic ibuprofen compared to placebo/no intervention in the prevention of PDA in preterm infants. Randomized controlled trials of prophylactic ibuprofen were identified by searching in The Cochrane Library, MEDLINE, CINAHL, EMBASE and trials registries in December 2010. Randomized or quasi-randomised controlled trials comparing ibuprofen with placebo/no intervention or other cyclo-oxygenase inhibitor drugs to prevent PDA in preterm and/or low birth weight infants. Outcomes data including presence of PDA on day three, need for surgical ligation or rescue treatment with cyclo-oxygenase inhibitors, mortality, intraventricular haemorrhage (IVH), renal, pulmonary and gastrointestinal complications were extracted. Meta-analyses were performed and treatment estimates are reported as typical weighted mean difference, relative risk (RR), risk difference (RD) and, if statistically significant, number needed to treat to benefit (NNT) or number needed to treat to harm (NNH) along with their 95% confidence intervals (CI). In this update, seven studies (n = 931) comparing prophylactic ibuprofen with placebo/no intervention are included. Ibuprofen decreased the incidence of PDA on day three [typical RR 0.36 (95% CI 0.29 to 0.46); typical RD -0.27 (95% CI -0.32 to -0.21); NNT 4 (95% CI 3 to 5)], decreased the need for rescue treatment with cyclo-oxygenase inhibitors and decreased the need for surgical ligation. Results from two studies administering oral ibuprofen had similar results, but showed an increased risk of gastrointestinal bleeding (NNH 4, 95% CI 2 to 17). In the control group the spontaneous closure rate was 58% by day three. Ibuprofen negatively affects renal function. No significant differences in mortality, IVH, chronic lung disease were found. Prophylactic use of ibuprofen decreased the incidence of PDA, decreased the need for rescue treatment with cyclo-oxygenase inhibitors and decreased the need for surgical closure. In the control group, the PDA closed spontaneously by day three in 58% of the neonates. Prophylactic treatment exposes many infants to a drug that has concerning renal and gastrointestinal side effects without conferring any important short-term benefits and is not recommended. Until long-term follow-up results are published from the trials included in this updated review, no further trials of prophylactic ibuprofen are recommended.


Simulating fishery-induced evolution in chinook salmon: the role of gear, location, and genetic correlation among traits.
Adaptation to human-modified ecosystems has been implicated in changing the life history of a number of wild animal populations, potentially contributing to their collapse. Fishing may be an important evolutionary force that can change the distribution of fitness-related traits; however, the magnitude and direction of the evolutionary response may be influenced by different management strategies. Most phenotypic traits subject to human-induced selection are simultaneously influenced by the environment and by genetic variation, and many traits are genetically correlated. Here, we evaluated the evolutionary outcomes of harvest activities on mean length and age at maturity in a fish population by coupling a multivariate quantitative genetic model with a Leslie life history matrix model. Lengths-at-ages were treated as genetically correlated characters parameterized from empirical data on chinook salmon (Oncorhynchus tshawytscha) populations. Using simulations, we explored the outcomes of 100 years of harvest using gill nets, which impose disruptive selection, or longlines, which impose minimum size selection, that targeted immature individuals in the high seas or maturing individuals in terminal spawning areas. Response in mean length and age depended on selection differentials imposed by harvest (which depended in turn on fishing location, gear type, and proportion of the population harvested) and on the genetic correlations between traits. Mean length was strongly influenced by the selection differential of the most abundant age class. Large differences in response were observed between the high-seas fishery, where the most abundant age was the youngest age vulnerable to harvest, compared to the terminal area fishery, where an older age class was most abundant. We observed a substantial difference in response between gill nets and longlines in the terminal fishery only. The evolution of mean age of mature individuals was less predictable, but generally increased as length decreased and decreased as length increased. The model presented here has potential for incorporating empirical data into fisheries forecasting and therefore provides a powerful means of integrating evolutionary considerations into harvest management.


Speckle reduction in optical coherence tomography images by use of a spatially adaptive wavelet filter.
A spatially adaptive two-dimensional wavelet filter is used to reduce speckle noise in time-domain and Fourier-domain optical coherence tomography (OCT) images. Edges can be separated from discontinuities that are due to noise, and noise power can be attenuated in the wavelet domain without significantly compromising image sharpness. A single parameter controls the degree of noise reduction. When this filter is applied to ophthalmic OCT images, signal-to-noise ratio improvements of >7 dB are attained, with a sharpness reduction of <3%.


Femtosecond spectral pulse shaping with holographic gratings recorded in photopolymerizable glasses.
The majority of the applications of ultrashort laser pulses require a control of its spectral bandwidth. In this paper we show the capability of volume phase holographic gratings recorded in photopolymerizable glasses for spectral pulse reshaping of ultrashort laser pulses originated in an Amplified Ti: Sapphire laser system and its second harmonic. Gratings with high laser induce damage threshold (LIDT) allowing wide spectral bandwidth operability satisfy these demands. We have performed LIDT testing in the photopolymerizable glass showing that the sample remains unaltered after more than 10 million pulses with 0,75 TW/cm2 at 1 KHz repetition rate. Furthermore, it has been developed a theoretical model, as an extension of the Kogelnik's theory, providing key gratings design for bandwidth operability. The main features of the diffracted beams are in agreement with the model, showing that non-linear effects are negligible in this material up to the fluence threshold for laser induced damage. The high versatility of the grating design along with the excellent LIDT indicates that this material is a promising candidate for ultrashort laser pulses manipulations.


Cluster of differentiation 36 gene polymorphism (rs1761667) is associated with dietary MUFA intake and hypertension in a Japanese population.
Cluster of differentiation 36 (CD36) is a membrane receptor expressed on a wide variety of human cells. CD36 polymorphisms are reportedly associated with oral fat perception, dietary intake and metabolic disorders. The present study examined associations of two CD36 polymorphisms (rs1761667 and rs1527483) and dietary fat intake, and metabolic phenotypes in a Japanese population. This cross-sectional study was conducted based on clinical information collected from health check-ups in Japan (n 495). Dietary nutrient intake was estimated from a validated short FFQ and adjusted for total energy intake using the residual method. Mean blood pressure was calculated from systolic blood pressure (SBP) and diastolic blood pressure (DBP). Hypertension was defined as SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg, or use of antihypertensive drugs. Genotyping was performed using PCR with confronting two-pair primers method. Mean age was 63·4 (sd 9·9) years. Individuals with the AA genotype showed higher total fat and MUFA intake (standardised β = 0·110 and 0·087, P = 0·01 and 0·05, respectively) compared with the GG and GA genotypes. For metabolic phenotypes, the AA genotype of rs1761667 had a lower blood pressure compared with the GG genotype (standardised β = -0·123, P = 0·02). Our results suggested that the AA genotype of rs1761667 in the CD36 gene was associated with higher intake of total fat and MUFA and lower risk of hypertension in a Japanese population.


Thioflavin-based molecular probes for application in Alzheimer's disease: from in silico to in vitro models.
Alzheimer's disease (AD) is a neurological disease of confusing causation with no cure or prevention available. The definitive diagnosis is made postmortem, in part through the presence of amyloid-beta plaques in the brain tissue, which can be done with the small molecule thioflavin-T (ThT). Plaques are also found to contain elevated amounts of metal ions Cu(ii) and Zn(ii) that contribute to the neurotoxicity of amyloid-beta (Aβ). In this paper, we report in silico, in vitro, and ex vivo studies with ThT-derived metal binders 2-(2-hydroxyphenyl)benzoxazole (HBX), 2-(2-hydroxyphenyl)benzothiazole (HBT) and their respective iodinated counterparts, HBXI and HBTI. They exhibit low cytotoxicity in a neuronal cell line, potential blood-brain barrier penetration, and interaction with Aβ fibrils from senile plaques present in human and transgenic mice AD models. Molecular modelling studies have also been undertaken to understand the prospective ligand-Aβ complexes as well as to rationalize the experimental findings. Overall, our studies demonstrate that HBX, HBT, HBXI, and HBTI are excellent agents for future use in in vivo models of AD, as they show in vitro efficacy and biological compatibility. In addition to this, we present the glycosylated form of HBX (GBX), which has been prepared to take advantage of the benefits of the prodrug approach. Overall, the in vitro and ex vivo assays presented in this work validate the use of the proposed ThT-based drug candidate series as chemical tools for further in vivo development.


The Possible Effects of High Vessel Traffic on the Physiological Parameters of the Critically Endangered Yangtze Finless Porpoise (Neophocaena asiaeorientalis ssp. asiaeorientalis).
Background: Poyang is the largest freshwater lake in China, where the acoustic environment and space for the critically endangered Yangtze finless porpoises (YFPs) has been altered by heavy vessel traffic and dredging activities. The density of vessel and the rate of dredging increases annually, especially in the area with the highest density of YFPs. The heavy vessel traffic can cause an increase in the physical activities and direct physical injuries to the YFPs. Furthermore, noise is a potent stressor to all cetaceans irrespective of age and can compromise all their physiological functions. The objective of this study was to examine the possible effects of heavy vessel traffic and dredging on the biochemistry, hematology, adrenal, thyroid, and reproductive hormones of two different YFP populations. One population was living in Poyang Lake and the second living in the Tian-E-Zhou Oxbow which is a semi-natural resserve. Results: The results showed statistically significantly higher levels of serum cortisol, fT3, fT4, and lowered testosterone in both adult and juvenile YFPs living in Poyang Lake vs. adult YFPs living in the Tian-E-Zhou Oxbow. The serum biochemical parameters (Aspartate Amino Transferase, Alkaline Phosphatase, High Density Lipoprotein cholesterol ratio, Globulin, Uric acid, Glucose, K+, and Amylase) and the hematology parameters (Red Blood Cells, Hematocrit, Mean Corpuscular Volume, White Blood Cells, and Eosinophils) were statistically significantly higher in the adult Poyang Lake YFPs vs. adult Tian-E-Zhou Oxbow YFPs. On the other hand, adult males of the Tian-E-Zhou Oxbow also showed significantly higher levels of the serum biochemical parameters (Total Cholesterol, Light Density Lipoprotein cholesterol, Direct Bilirubin, Albumin, Lactate Dehydrogenase, CO2, and Na+) and the blood parameters (Mean Corpuscular Hemoglobin and Mean Corpuscular Hemoglobin Concentration). In Poyang Lake YFPs, various parameters showed significantly positive (fT4, amylase, neutrophil, Ca+2) or negative (total protein, lymphocyte) correlations with cortisol levels. Conclusions: The hyperactivity of adrenal glands in response to heavy vessel traffic and dredging resulted in significantly elevated cortisol levels in Poyang Lake YFPs. The higher cortisol level could possibly have affected various hormonal, hematological, and biochemical parameters, and ultimately the YFPs physiology.


Surface Reactivity of Ag-Modified Ceria to Hydrogen: A Combined Experimental and Theoretical Investigation.
We investigate the mechanism of H2 activation on Ag-modified cerium oxide surfaces, of interest for different catalytic applications. The study is performed on thin epitaxial cerium oxide films, investigated by X-ray photoemission spectroscopy to assess the changes of both the Ag oxidation state and the concentration of Ce3+ ions, O vacancies, and hydroxyl groups on the surface during thermal reduction cycles in vacuum and under hydrogen exposure. The results are interpreted using density functional theory calculations to model pristine and Ag-modified ceria surfaces. Although the reactivity of ceria toward H2 oxidation improves when a fraction of Ce cations is substituted with Ag, the concentration of reduced Ce3+ ions in Ag-modified ceria is found to be lower than in pure ceria under the same conditions. This behavior is observed even though the number of surface oxygen vacancies caused by the thermal treatment under hydrogen exposure is larger for the Ag-modified surface. These results are explained in terms of a change of the oxidation state of the surface Ag, which is able to acquire some of the extra surface electrons created by the oxygen vacancies and the adsorbed hydrogen atoms. Our findings provide new insights into the reactivity of Ag-modified ceria, which has been proposed as a promising alternative to platinum electrodes in electrochemical devices.


Beyond motor scheme: a supramodal distributed representation in the action-observation network.
The representation of actions within the action-observation network is thought to rely on a distributed functional organization. Furthermore, recent findings indicate that the action-observation network encodes not merely the observed motor act, but rather a representation that is independent from a specific sensory modality or sensory experience. In the present study, we wished to determine to what extent this distributed and 'more abstract' representation of action is truly supramodal, i.e. shares a common coding across sensory modalities. To this aim, a pattern recognition approach was employed to analyze neural responses in sighted and congenitally blind subjects during visual and/or auditory presentation of hand-made actions. Multivoxel pattern analyses-based classifiers discriminated action from non-action stimuli across sensory conditions (visual and auditory) and experimental groups (blind and sighted). Moreover, these classifiers labeled as 'action' the pattern of neural responses evoked during actual motor execution. Interestingly, discriminative information for the action/non action classification was located in a bilateral, but left-prevalent, network that strongly overlaps with brain regions known to form the action-observation network and the human mirror system. The ability to identify action features with a multivoxel pattern analyses-based classifier in both sighted and blind individuals and independently from the sensory modality conveying the stimuli clearly supports the hypothesis of a supramodal, distributed functional representation of actions, mainly within the action-observation network.


Mimicry and play initiation in 18-month-old infants.
Across two experiments, we examined the relationship between 18-month-old infants' mimicry and social behavior - particularly invitations to play with an adult play partner. In Experiment 1, we manipulated whether an adult mimicked the infant's play or not during an initial play phase. We found that infants who had been mimicked were subsequently more likely to invite the adult to join their play with a new toy. In addition, they reenacted marginally more steps from a social learning demonstration she gave. In Experiment 2, infants had the chance to spontaneously mimic the adult during the play phase. Complementing Experiment 1, those infants who spent more time mimicking the adult were more likely to invite her to play with a new toy. This effect was specific to play and not apparent in other communicative acts, such as directing the adult's attention to an event or requesting toys. Together, the results suggest that infants use mimicry as a tool to establish social connections with others and that mimicry has specific influences on social behaviors related to initiating subsequent joint interactions.