Trade-offs in using European forests to meet climate objectives.
The Paris Agreement promotes forest management as a pathway towards halting climate warming through the reduction of carbon dioxide (CO2) emissions1. However, the climate benefits from carbon sequestration through forest management may be reinforced, counteracted or even offset by concurrent management-induced changes in surface albedo, land-surface roughness, emissions of biogenic volatile organic compounds, transpiration and sensible heat flux2-4. Consequently, forest management could offset CO2 emissions without halting global temperature rise. It therefore remains to be confirmed whether commonly proposed sustainable European forest-management portfolios would comply with the Paris Agreement-that is, whether they can reduce the growth rate of atmospheric CO2, reduce the radiative imbalance at the top of the atmosphere, and neither increase the near-surface air temperature nor decrease precipitation by the end of the twenty-first century. Here we show that the portfolio made up of management systems that locally maximize the carbon sink through carbon sequestration, wood use and product and energy substitution reduces the growth rate of atmospheric CO2, but does not meet any of the other criteria. The portfolios that maximize the carbon sink or forest albedo pass only one-different in each case-criterion. Managing the European forests with the objective of reducing near-surface air temperature, on the other hand, will also reduce the atmospheric CO2 growth rate, thus meeting two of the four criteria. Trade-off are thus unavoidable when using European forests to meet climate objectives. Furthermore, our results demonstrate that if present-day forest cover is sustained, the additional climate benefits achieved through forest management would be modest and local, rather than global. On the basis of these findings, we argue that Europe should not rely on forest management to mitigate climate change. The modest climate effects from changes in forest management imply, however, that if adaptation to future climate were to require large-scale changes in species composition and silvicultural systems over Europe5,6, the forests could be adapted to climate change with neither positive nor negative climate effects.


Reconstructing an ultrametric galled phylogenetic network from a distance matrix.
Given a distance matrix M that specifies the pairwise evolutionary distances between n species, the phylogenetic tree reconstruction problem asks for an edge-weighted phylogenetic tree that satisfies M, if one exists. We study some extensions of this problem to rooted phylogenetic networks. Our main result is an O(n(2) log n)-time algorithm for determining whether there is an ultrametric galled network that satisfies M, and if so, constructing one. In fact, if such an ultrametric galled network exists, our algorithm is guaranteed to construct one containing the minimum possible number of nodes with more than one parent (hybrid nodes). We also prove that finding a largest possible submatrix M' of M such that there exists an ultrametric galled network that satisfies M' is NP-hard. Furthermore, we show that given an incomplete distance matrix (i.e. where some matrix entries are missing), it is also NP-hard to determine whether there exists an ultrametric galled network which satisfies it.


Effects of artificial rearing on electrophysiology and behavior in adult rats.
Maternal separation during crucial periods of development can lead to both physiological and behavioral sequelae. However, the exact consequences of maternal separation are paradigm dependent. The present study utilized complete artificial rearing (AR) to evaluate the effects of maternal separation on behavioral and electrophysiological functioning. In this procedure thermoregulation and weight gain progress are normal, but pups are deprived of any maternal influence from postnatal day 4 to 12. Artificial rearing was found to have no effect on EEG as assessed using spectral analyses. However, the N1 component of the auditory event-related potential (ERP) in artificially reared rats was significantly delayed. Artificial rearing had no effect on overall locomotor activity, but artificially reared rats were more behaviorally inhibited than suckled controls in the open field. This study suggests that artificial rearing or chronic maternal separation (24 h/day from PN4 to PN12), while not producing gross behavioral effects, can produce selective enduring alterations in neurosensory responses.


Effect of cationic liposomes in an in vitro transcription and translation system.
The effects of cationic liposomes complexed with plasmid DNA on the process of transcription was examined using a recently developed rapid cell free translation system. The findings indicate that the liposome itself inhibited the process when the ratio of DNA/liposome typically used in transfection studies was used.


Anxiety and depression in patients with end-stage renal disease: impact and management challenges - a narrative review.
Psychiatric disorders commonly co-exist with the diagnosis of chronic kidney disease (CKD). Research on depression and CKD has increased to a great extent. Multiple studies have demonstrated that depression is more prevalent in CKD and that end-stage renal disease is a robust risk factor for adverse outcomes such as hospitalization and mortality, yet these are often underdiagnosed or untreated. This review provides a selective overview on the prevalence rates of depression and anxiety in patients with CKD and across renal replacement therapies, the factors most consistently associated with symptoms of distress and their clinical implications. Finally, treatment and management strategies from relevant literature are appraised and discussed.


Recent developments in emerging microimmunoassays.
Creative and novel microimmunoassay approaches continue to proliferate across many platforms originating from several fields of study. These efforts are aimed at improving one or more metrics for clinical tests, including improved sensitivity, increased speed, reduced cost, smaller sample size, the ability to analyze multiple antigens in parallel and ease of use. Many approaches focus on the production of microarrays that accomplish standard assays in parallel, or mobile solid-support formats to overcome issues of high background noise and long incubation times. In this article, innovative developments beyond existing commercial tests in the microimmunoassay arena are reviewed, covering January 2008 to April 2012. These developing experimental platforms are discussed in terms of their ability to augment or replace current commercial approaches.


Immobilization and tagging of muskoxen (Ovibos moschatus) in Jameson Land, northeastern Greenland.
In July 1982 and 1983, 491 muskoxen were handled in a tagging project in Jameson Land, northeastern Greenland. Groups of muskoxen as well as single individuals were rounded up effectively by Greenland huskies and kept in an accessible position suitable for injection of immobilizing drugs. Standard doses of drugs were developed for each age class. For adults the dose used was 2 mg etorphine, 30 mg xylazine and 200 IU hyaluronidase. For yearlings the xylazine was reduced to 20 mg while the etorphine and hyaluronidase remained at 2 and 200, respectively. For calves the doses were 0.5 mg etorphine with 200 IU hyaluronidase. The narcotic antagonist used was deprenorphine (used with hyaluronidase) administered via the intramuscular route so that all animals in any group would recover more or less simultaneously.


Pellet characteristics and drug release when the form of propranolol is fixed as moles or mass in formulations for extruded and spheronized Carbopol-containing pellets.
Characteristics of Carbopol-containing pellets have been shown to be dependent on the form of the weakly basic drug, propranolol, when the drug forms are fixed as masses in the formulations. To further investigate the effect of the drug forms on pellet and drug release characteristics, the drug forms were incorporated as a fixed number of moles in the formulation. Forms of propranolol, viz. the free base and the hydrochloride and maleate salt forms, resulted in different yield, roundness, smoothness, and friability, but the average pellet diameter was not affected. The free base form was released more slowly than the other two forms. Mathematical analysis of the release data revealed that Fickian diffusion and polymer relaxation contributed to the release mechanism in each case, although polymer relaxation was more influential with the free base form.


Identification of Nephrogenic Therapeutic Biomarkers of Wilms Tumor Using Machine Learning.
Wilms tumor is the most common renal malignancy in children, with a survival rate of more than 90%; however, treatment outcomes for certain patient subgroups, such as those with bilateral and recurrent diseases, remain significantly below this survival rate. Therefore, it remains essential to identify new biomarkers and develop effective therapeutic strategies. Based on the Therapeutically Applicable Research to Generate Effective Treatments and Gene Expression Omnibus RNA microarray datasets, we have identified eight differentially expressed genes in Wilms tumors as renal-specific in 33 randomly selected adult tumors. The risk model, constructed using survival forest and multivariate Cox regression, can effectively predict the prognosis; the risk score is an independent prognostic factor in Wilms tumor. Gene set enrichment analysis showed that most of the signature genes were involved in regulating human development-related pathways. At the same time, patients in the high-risk group exhibited more sensitive immunological and chemotherapeutic properties than those in the low-risk group. These results provide new insights into personalized and precise Wilms tumor treatment strategies.


Critical assessment of phospholipid measurement in amniotic fluid.
We assessed several methods of inorganic phosphate assay for their suitability in estimating phospholipids in digested extracts of amniotic fluids. The extraction and digestion procedures used for phospholipids from amniotic fluid were also examined critically. The effect of contamination by blood or obstetric cream has been examined. Accordingly, we suggest a method for measuring total phospholipids in amniotic fluids, and results of it are compared with the lecithin/sphingomyelin ratio measurement in some clinical situations.


Color vision tests for early detection of antiepileptic drug toxicity.
A previous suggestion that antiepileptic drugs may induce color vision deficiencies prompted us to examine whether color vision deficiencies may occur at lower drug serum concentrations than those associated with symptoms of neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of valproic acid, phenytoin, or carbamazepine; 18 patients did not receive antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100-hue test, spectral sensitivity, and the newly developed tritan screening plates. Patients treated with phenytoin or carbamazepine developed blue-yellow color vision deficiencies. In contrast, patients exposed to valproic acid or receiving no drug treatment showed normal color vision. There was a significant correlation (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine and blue-yellow color vision deficiencies. In contrast, we found no correlation between these signs of neurotoxicity and the drug serum concentrations (p = 0.0637). Color vision testing in epileptic patients treated with phenytoin or carbamazepine appears to be a sensitive method for early detection and monitoring of clinical neurotoxicity.


Event boundaries do not cause the immediate extinction deficit after Pavlovian fear conditioning in rats.
Recent work reveals that the extinction of conditioned fear depends upon the interval between conditioning and extinction. Extinction training that takes place within minutes to hours after fear conditioning fails to produce a long-term extinction memory, a phenomenon known as the immediate extinction deficit (IED). Neurobiological evidence suggests that the IED results from stress-induced dysregulation of prefrontal cortical circuits involved in extinction learning. However, a recent study in humans suggests that an "event boundary" between fear conditioning and extinction protects the conditioning memory from interference by the extinction memory, resulting in high levels of fear during a retrieval test. Here, we contrast these hypotheses in rats by arranging extinction trials to follow conditioning trials with or without an event boundary; in both cases, extinction trials are delivered in proximity to shock-elicited stress. After fear conditioning, rats either received extinction trials 60-sec after the last conditioning trial (continuous, no event boundary) or 15-minutes after conditioning (segmented, a standard "immediate" extinction procedure associated with an event boundary). Both groups of animals showed decreases in conditional freezing to the auditory conditioned stimulus (CS) during extinction and exhibited an equivalent IED relative to non-extinguished controls when tested 48 hours later. Thus, eliminating the event boundary between conditioning and extinction with the continuous extinction procedure did not prevent the IED. These data suggest that the IED is the result of shock-induced stress, rather than boundary-induced reductions in memory interference.


Comparison of Focused Ultrasound Surgery and Hysteroscopic Resection for Treatment of Submucosal Uterine Fibroids (FIGO Type 2).
The aim of the study described here was to compare the effectiveness of focused ultrasound surgery (FUS), which uses high-intensity focused ultrasound to perform tissue ablation, with that of hysteroscopic transcervical resection of myoma (TCRM) for the treatment of type 2 submucosal fibroids. A prospective cohort study was performed in patients who underwent FUS or TCRM from January 2012 to December 2014. Uterine Fibroid Symptom (UFS) and Quality of Life (QoL) questionnaires were used to measure fibroid-related symptoms and quality of life before and at 3, 6 and 12 mo after treatment. Technical results, adverse events and post-operative recovery times of both groups were also compared. A total of 81 patients with at least one type 2 submucosal fibroid were enrolled. The mean diameter of type 2 submucosal fibroids was 3.8 ± 0.9 cm (range: 2.0-5.0 cm) for 39 patients in the FUS group and 3.5 ± 0.8 cm (range: 2.0-4.8 cm) for the 42 patients enrolled in the TCRM group. No major complication occurred in any patients for either treatment. In both groups, the UFS score decreased significantly and the QoL score increased significantly from baseline successively at 3, 6 and 12 mo post-treatment (p < 0.05). Time spent in hospital post-treatment was significantly shorter (2.56 ± 0.98 d) for the FUS group compared with the TCRM group (3.31 ± 0.60 d) (p < 0.05). Time to return to work after treatment was also significantly shorter for the FUS group (3.14 ± 0.83 d) than for the TCRM group (6.09 ± 0.9 d) (p < 0.05). FUS and TCRM are both tolerable and effective treatments with significant improvement of symptom and quality of life for patients with type 2 submucosal fibroids ≤5 cm in diameter.


Regulation of spermatogonial stem cell self-renewal in mammals.
Mammalian spermatogenesis is a classic adult stem cell-dependent process, supported by self-renewal and differentiation of spermatogonial stem cells (SSCs). Studying SSCs provides a model to better understand adult stem cell biology, and deciphering the mechanisms that control SSC functions may lead to treatment of male infertility and an understanding of the etiology of testicular germ cell tumor formation. Self-renewal of rodent SSCs is greatly influenced by the niche factor glial cell line-derived neurotrophic factor (GDNF). In mouse SSCs, GDNF activation upregulates expression of the transcription factor-encoding genes bcl6b, etv5, and lhx1, which influence SSC self-renewal. Additionally, the non-GDNF-stimulated transcription factors Plzf and Taf4b have been implicated in regulating SSC functions. Together, these molecules are part of a robust gene network controlling SSC fate decisions that may parallel the regulatory networks in other adult stem cell populations.


Observations on the urine metabolic profile of codeine in pain patients.
This retrospective data analysis explored the relationship between codeine and its metabolites morphine, hydrocodone and hydromorphone. The objectives were: (i) to determine urine concentrations and mole fractions of codeine and metabolites and (ii) to examine the effect of cytochrome P450 (CYP) 2D6 inhibition on metabolite mole fractions. De-identified urine specimens were collected between September 2010 and July 2011 and analyzed using LC-MS-MS to determine codeine, morphine, hydrocodone and hydromorphone concentrations. Geometric mean urine concentrations were 0.833, 0.085 and 0.055 for morphine, hydrocodone and hydromorphone, respectively. Mole fractions were 0.23, 0.025 and 0.014 for morphine, hydrocodone and hydromorphone, respectively. The fraction of excreted codeine in the urine increased (slope = 0.06 ± .01, R² = 0.02) with total moles. As the total amount of codeine and metabolites increased, the fraction of codeine increased, while the fraction of active metabolites decreased. CYP2D6 inhibition with paroxetine, fluoxetine, bupropion and methadone significantly decreased the fraction of morphine excreted. The prevalence of codeine metabolism to morphine was considerably higher than codeine to hydrocodone. The urine concentration of codeine excreted was the greatest, followed by morphine and hydrocodone. Subjects should be monitored during concomitant use of codeine and CYP2D6 inhibitors as this affects the amount of morphine metabolite formation.


Nrg1 Regulates Cardiomyocyte Migration and Cell Cycle in Ventricular Development.
Cardiac ventricles provide the contractile force of the beating heart throughout life. How the primitive endocardium-layered myocardial projections called trabeculae form and mature into the adult ventricles is of great interest for biology and regenerative medicine. Trabeculation is dependent on the signaling protein Nrg1 (neuregulin-1). However, the mechanism of action of Nrg1 and its role in ventricular wall maturation are poorly understood. We investigated the functions and downstream mechanisms of Nrg1 signaling during ventricular chamber development using confocal imaging, transcriptomics, and biochemical approaches in mice with cardiac-specific inactivation or overexpression of Nrg1. Analysis of cardiac-specific Nrg1 mutant mice showed that the transcriptional program underlying cardiomyocyte-oriented cell division and trabeculae formation depends on endocardial Nrg1 to myocardial ErbB2 (erb-b2 receptor tyrosine kinase 2) signaling and phospho-Erk (phosphorylated extracellular signal-regulated kinase; pErk) activation. Early endothelial loss of Nrg1 and reduced pErk activation diminished cardiomyocyte Pard3 and Crumbs2 (Crumbs Cell Polarity Complex Component 2) protein and altered cytoskeletal gene expression and organization. These alterations are associated with abnormal gene expression related to mitotic spindle organization and a shift in cardiomyocyte division orientation. Nrg1 is crucial for trabecular growth and ventricular wall thickening by regulating an epithelial-to-mesenchymal transition-like process in cardiomyocytes involving migration, adhesion, cytoskeletal actin turnover, and timely progression through the cell cycle G2/M phase. Ectopic cardiac Nrg1 overexpression and high pErk signaling caused S-phase arrest, sustained high epithelial-to-mesenchymal transition-like gene expression, and prolonged trabeculation, blocking compact myocardium maturation. Myocardial trabecular patterning alterations resulting from above- or below-normal Nrg1-dependent pErk activation were concomitant with sarcomere actin cytoskeleton disorganization. The Nrg1 loss- and gain-of-function transcriptomes were enriched for Yap1 (yes-associated protein-1) gene signatures, identifying Yap1 as a potential downstream effector. Furthermore, biochemical and imaging data reveal that Nrg1 influences pErk activation and Yap1 nuclear-cytoplasmic distribution during trabeculation. These data establish the Nrg1-ErbB2/ErbB4-Erk axis as a crucial regulator of cardiomyocyte cell cycle progression and migration during ventricular development.


Nuclear triiodothyronine binding in mononuclear leukocytes in normal subjects and obese patients before and after fasting.
We evaluated the maximum binding capacity (MBC) and dissociation constant (Kd) of nuclear T3 receptors (NT3R) in mononuclear cells in normal and obese subjects before and after fasting. Mononuclear cells were isolated by isopycnic centrifugation of 50 ml heparinized blood underlayered with Ficoll-Paque. From 1-5 x 10(6) cells (12-60 microgram DNA) were incubated for 2 h at 37 C in 0.5 ml Ham's F-10 medium with 0.5% bovine serum albumin, 25 mM Hepes buffer (pH 7.4), and six T3 concentrations, each in triplicate (free T3 from 7 x 10(-13) to 5 x 10(-11) and 1.5 x 10(-8) M). Nuclei were isolated from washed cells in sucrose (0.25 M)-Tris (20 mM; pH 7.85)-MgCl2 (1.1 mM) containing 0.5% Triton X-100. Cells took up approximately 5% of the medium T3, and this was not significantly influenced by the T3 concentrations in the medium. About 10% of the cellular T3 was bound to nuclei at 7 x 10(-13) M free T3 in the medium. Nuclear binding in the presence of 1.5 x 10(-8) M free T3 was approximately 20% of that at 7 x 10(-13) M. T4 could compete with T3 for nuclear binding, but it was less than 10% as effective as T3 based on free hormone concentrations. MBC and Kd values of NT3R were the means of two separate determinations on successive days with coefficients of variation of 26% and 28%, respectively. The MBC of NT3R in 9 normal subjects was 2.3 +/- 0.4 (SD) x 10(-15) mol T3/100 microgram DNA, and the apparent Kd was 2.3 +/- 0.5 (SD) x 10(-11) M free T3. For 10 obese subjects, the MBC was 2.5 +/- 0.8 (SD) x 10(-15) mol T3/100 microgram DNA, and the Kd was 2.4 +/- 0.6 (SD) x 10(-11) M free T3. During a 16-day total fast, 7 patients lost 10 +/- 2 kg, and the mean serum T3 decreased by 60%. However, the MBC [2.7 +/- 0.9 vs. 2.4 +/- 0.4 (fasted) x 10(-15) mol/100 microgram DNA] and Kd [2.4 +/- 0.7 vs 2.1 +/- 0.4 (fasted) x 10(-11) M free T3] were not significantly altered. Circulating human mononuclear cells contain limited capacity, high affinity binding sites for T3. We are unable to detect differences in either the MBC or Kd for these sites between lean and obese subjects, nor does fasting alter either of these parameters. If fasting alters NT3R in man, such changes are not detectable in circulating mononuclear cells using these techniques.


Circadian variation in 5-hydroxyindoleacetic acid levels in human cerebrospinal fluid.
Circadian variation of 5-hydroxyindoleacetic acid (5-HIAA) in the ventricular fluid of 5 neurosurgical cases is examined. The 5-HIAA level increases progressively during the day (highest values at 24.00 h) and returns to the initial level the following day at 6.00 h. The results are discussed.


Evaluating the factor structure, item analyses, and internal consistency of hospital anxiety and depression scale in Iranian infertile patients.
The hospital anxiety and depression scale (HADS) is a common screening tool designed to measure the level of anxiety and depression in different factor structures and has been extensively used in non-psychiatric populations and individuals experiencing fertility problems. The aims of this study were to evaluate the factor structure, item analyses, and internal consistency of HADS in Iranian infertile patients. This cross-sectional study included 651 infertile patients (248 men and 403 women) referred to a referral infertility Center in Tehran, Iran between January 2014 and January 2015. Confirmatory factor analysis was used to determine the underlying factor structure of the HADS among one, two, and three-factor models. Several goodness of fit indices were utilized such as comparative, normed and goodness of fit indices, Akaike information criterion, and the root mean squared error of approximation. In addition to HADS, the Satisfaction with Life Scale questionnaires as well as demographic and clinical information were administered to all patients. The goodness of fit indices through CFAs exposed that three and one-factor model provided the best and worst fit to the total, male and female datasets compared to the other factor structure models for the infertile patients. The Cronbach's alpha for anxiety and depression subscales were 0.866 and 0.753 respectively. The HADS subscales significantly correlated with SWLS, indicating an acceptable convergent validity. The HADS was found to be a three-factor structure screening instrument in the field of infertility.


Successful gene expression analysis by multiplex, real-time, one-step RT-PCR, irrespective of the targets amplified.
Multiplex, real-time, one-step RT-PCR enables simultaneous quantification of several transcripts in one reaction vessel. This saves time and conserves precious sample material when analyzing the expression of reference and target genes in a particular sample. However, intensive PCR optimization is often required (1). We show that success in multiplex, real-time, one-step RT-PCR can be achieved at the first attempt with the QuantiTect Multiplex RT-PCR Kit, regardless of the combination of genes analyzed. In each of the multiplex assays carried out, all targets were amplified with high efficiency, which is important for precise relative quantification of gene expression levels by the deltadeltaC(T) method.


[Foreign genes expression in Wistar rats in vivo].
pN2-LacZ or pN2-CMV-ProUK plasmid DNA was separately injected into rat quadricept muscles and beta-galactosidase or Pro-UK was detected after 2 days. The expression of foreign genes lasted for at least 3 months. pN2-LacZ plasmid was injected into the left ventricular wall of the rat, and the expression of LacZ gene was more efficient than in the quadricept muscle. pN2-LacZ was also introduced into the rat arterial wall by balloon catheter. A new method was also found to improve the efficiency of foreign gene expression in muscle by stitching medical stitch containing plasmid DNA onto the quadricept muscle.


Novel role for p90 ribosomal S6 kinase in the regulation of cardiac myofilament phosphorylation.
In myocardium, the 90-kDa ribosomal S6 kinase (RSK) is activated by diverse stimuli and regulates the sarcolemmal Na(+)/H(+) exchanger through direct phosphorylation. Only limited information is available on other cardiac RSK substrates and functions. We evaluated cardiac myosin-binding protein C (cMyBP-C), a sarcomeric regulatory phosphoprotein, as a potential RSK substrate. In rat ventricular myocytes, RSK activation by endothelin 1 (ET1) increased cMyBP-C phosphorylation at Ser(282), which was inhibited by the selective RSK inhibitor D1870. Neither ET1 nor D1870 affected the phosphorylation status of Ser(273) or Ser(302), cMyBP-C residues additionally targeted by cAMP-dependent protein kinase (PKA). Complementary genetic gain- and loss-of-function experiments, through the adenoviral expression of wild-type or kinase-inactive RSK isoforms, confirmed RSK-mediated phosphorylation of cMyBP-C at Ser(282). Kinase assays utilizing as substrate wild-type or mutated (S273A, S282A, S302A) recombinant cMyBP-C fragments revealed direct and selective Ser(282) phosphorylation by RSK. Immunolabeling with a Ser(P)(282) antibody and confocal fluorescence microscopy showed RSK-mediated phosphorylation of cMyBP-C across the C-zones of sarcomeric A-bands. In chemically permeabilized mouse ventricular muscles, active RSK again induced selective Ser(282) phosphorylation in cMyBP-C, accompanied by significant reduction in Ca(2+) sensitivity of force development and significant acceleration of cross-bridge cycle kinetics, independently of troponin I phosphorylation at Ser(22)/Ser(23). The magnitudes of these RSK-induced changes were comparable with those induced by PKA, which phosphorylated cMyBP-C additionally at Ser(273) and Ser(302). We conclude that Ser(282) in cMyBP-C is a novel cardiac RSK substrate and its selective phosphorylation appears to regulate cardiac myofilament function.


Interoperator test for anatomical annotation of earprints.
As part of the Forensic Ear Identification (FearID) research project, which aims to obtain estimators for the strength of evidence of earmarks found on crime scenes, a large database of earprints (over 1200 donors) has been collected. Starting from a knowledge-based approach where experts add anatomical annotations of minutiae and landmarks present in prints, comparison of pairs of prints is done using the method of Vector Template Matching (VTM). As the annotation process is subjective, a validation experiment was performed to study its stability. Comparing prints on the basis of VTM, it appears that there are interoperator effects, individual operators yielding significantly more consistent results when annotating prints than different operators. The operators being well trained and educated, the observed variation on both clicking frequency and choice of annotation points suggests that implementation of the above is not the best way to go about objectifying earprint comparison. Processes like the above are relevant for any forensic science dealing with identification (e.g., of glass, tool marks, fibers, faces, fingers, handwriting, speakers) where manual (nonautomated) processes play a role. In these cases, results may be operator dependent and the dependencies need to be studied.


Adopting higher-order similarity relations for improved estimation of optical properties from subdiffusive reflectance.
Estimation of optical properties from subdiffusive reflectance acquired at short source-detector separations is challenging due to the sensitivity to the underlying scattering phase function. In recent studies, a second-order similarity parameter γ has been increasingly used alongside the absorption and reduced scattering coefficients to account for some of the phase function variability. By using Monte Carlo simulations, we show that the influence of the scattering phase function on the subdiffusive reflectance for the biologically relevant variations can be captured sufficiently well by considering γ and a third-order similarity parameter δ. Utilizing this knowledge, we construct an inverse model that estimates the absorption and reduced scattering coefficients, γ and δ, from spatially resolved reflectance. Nearly an order of magnitude smaller errors of the estimated optical properties are obtained in comparison to the inverse model that only composes γ.


[Comparative Evaluation of -blockers and If-Channel Inhibitor in Patients With Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction].
Treatment of patients with chronic heart failure (CHF) and preserved left ventricular (LV) ejection fraction remains largely empirical, as none of the methods of therapy improves the prognosis of patients. In a prospective randomized study on 126 patients with CHF and LV ejection fraction more or equal 50% we compared effectiveness of long-term treatment with bisoprolol (n=62) and ivabradine (n=64). Assessment of clinical status, exercise tolerance (ET), quality of life, blood level of N-terminal brain natriuretic peptide precursor, and parameters of echocardiography was performed at baseline and after 12 months of therapy. Unlike bisoprolol ivabradine, significantly improved exercise tolerance, quality of life, and reduced level of N-terminal brain natriuretic peptide precursor. Improvement of echocardiographic indices of active relaxation and compliance of the left ventricle was also observed. Key words: heart failure with preserved ejection fraction; ivabradine; bisoprolol; left ventricle diastolic dysfunction.


Few opportunities found for tuberculosis prevention among the urban poor.
Grady Memorial Hospital, a public hospital in Atlanta, Georgia, a city with high rates of tuberculosis. To identify specific points of contact with the public health system where high risk individuals could receive tuberculin testing and isoniazid preventive therapy. Patient interviews and medical chart reviews of tuberculosis patients diagnosed in hospital between October 1993 and December 1994. In total 151 tuberculosis patients participated: 80% were male, 89% African American, the mean age was 40; 50% were HIV co-infected. Three fourths reported no regular source of medical care. The only potential public health sites at least one third of the patients had encountered in the five years prior to tuberculosis diagnosis were correctional institutions (44%) and public hospital in-patient wards (37%). Duration of incarceration was six months or more in only 13% of patients. Of 108 (71%) patients who had identified substance abuse problems, only 25% had been in treatment programs. We conclude that most tuberculosis cases in this community occurred in persons with poor access to health care and few opportunities for public health intervention. Tuberculosis prevention for this high risk population can best be accomplished by focusing efforts on early case identification, completion of therapy and contact investigations.


The Impact of Social Well-Being on Population Diet Nutritional Value and Antiradical Status.
The paper presents the result of assessing the antiradical status of consumers (in the context of Russia) in connection with their well-being. This approach is based on a multistage study, in which the results of sociological surveys were applied, as well as estimates of the antiradical potential (ARP) of diets obtained using neural networks, bootstrapping the chemical composition of diets, and calculating reference values using mathematical models. The paper presents data collected from residents living in the territories of at least 21 regions and cities of Russia: Magadan, Saint Petersburg, Moscow, Krasnodar, Lipetsk, Vladivostok, Novosibirsk, Omsk, Voronezh, etc. A total of 1001 people were interviewed, which, according to our calculations, gives a margin of error in value of approximately 3.1%. To calculate the lack of vitamins in the diets of residents of the Russian Federation, data on the chemical composition of food products from the FNDDS database were used. The assessment of dietary habits showed a lack of vitamins below the recommended level in 73% of Russians for vitamin D, 59% for retinol, 38% for β-carotenes, 13% for vitamin E, and 6% for ascorbic acid. The study showed that at least 36% of the Russian population has a low antiradical status, while it was found that "poor" consumers are more likely to consume economically more expensive foods (in terms of their nutritional value). The "poor" segments of the population consume 180-305% more canned food and 38-68% more sweet carbonated drinks than other social groups, but their consumption of vegetables is 23-48% lower. On the contrary, "wealthy" consumers consume 17-25% more complex (varied) dishes, 10-68% more fresh vegetables, and 8-39% more fish. From the obtained values it follows that consumers with low levels of ARP in their diets are in a group with an increased probability of a number of "excess" diseases (diseases of the cardiovascular system, obesity, etc.). In general, the ARP values of food consumed for low-income segments of the population were 2.3 times lower (the ratio was calculated as the percentage of consumers below the level of 11,067 equivalents necessary for the disposal of free radicals generated in the human body per day) than for those who can afford expensive food (consumers with high income). A simple increase in consumption of unbalanced foods, in our opinion, will only contribute to the entry of these consumers into the "average diet trap". All this makes it imperative to develop comprehensive measures to create a new concept of public catering; otherwise, we can expect a reduction in both the health of the population and the performance of the economy of the whole country.


Evaluating the Potential for Recovery of Consciousness in the Intensive Care Unit.
Evaluating patients in the intensive care unit (ICU) with disorders of consciousness has prognostic implications. When brainstem functions are intact, the neurologist must use ancillary testing to help determine prognosis. This article addresses the challenges of arriving at prognoses in patients with hypoxic-ischemic encephalopathy and traumatic brain injury (TBI) and discusses strategies for dealing with these challenges. This has some relevance to other conditions that are capable of causing irreversible brain damage. Although practice parameters formulated by an American Academy of Neurology (AAN) subcommittee in 2006 were reliable for evaluating patients with hypoxic-ischemic encephalopathy who did not receive hypothermia, the advent of hypothermia has shown that some of these prognostic features were unreliable. Some patients with TBI thought to be vegetative have been found to have cognitive responses. These revelations require neurologists to reconsider prognostic strategies. To arrive at a more accurate prognosis, it is best to employ multiple pieces of evidence and incorporate the most updated information from the literature. In some cases, newer technologies can provide further insights into cortical function in behaviorally unresponsive patients.


A review of the factors influencing adoption of digital health applications for people living with dementia.
Researchers have used various theories and models to understand technology adoption, however, with the growing interest and availability of mobile applications (apps) for people living with dementia, it is desirable to have a broader insight into how technology adoption may be further improved. This paper aims to explore the factors influencing the adoption of digital health applications for people living with dementia and add to the current literature on this topic. Searches were conducted in CINHAL, Web of Science, Psych Info, ProQuest Health and Medical, IEEE Xplore and Scopus. Citation searching and handsearching were used in the identification of other studies. Following an assessment of relevancy, nine studies remained and are included within this review. Methodological quality was assessed using The Mixed Methods Appraisal Tool (MMAT). A thematic analysis was used for the data synthesis of included studies. Each study reported on different types of apps. From the synthesis of included studies, four analytic themes were identified; Theme 1: Personal and contextual factors; Theme 2: Perceived value and benefit; Theme 3: Design and content of app; and Theme 4: Digital Literacy and Confidence. People are diverse and so are their reasons for the adoption of apps. These findings provide an insight into the range of factors that impact the adoption of apps for people living with dementia. Understanding the factors that impact the adoption of mobile applications is critical to their success. These findings can be beneficial for app developers and for people living with dementia and their carers.


Enamel proteases reduce amelogenin-apatite binding.
Organic matrix degradation and crystal maturation are extracellular events that occur simultaneously during enamel biomineralization. We hypothesized that enamel proteases control amelogenin-mineral interaction, which, in turn can affect crystal nucleation, organization, and growth. We used a recombinant amelogenin (rP172), a homolog of its major cleavage product (rP148), and a native amelogenin lacking both N- and C-termini (13k). We compared apatite binding affinity between amelogenins and their digest products during proteolysis. We further compared binding affinity among the 3 amelogenins using a Langmuir model for protein adsorption. Amelogenin-apatite binding affinity was progressively reduced with the proteolysis at the C- and N- termini by recombinant pig MMP-20 (rpMMP20) and recombinant human kallikrein-4 (rhKLK4), respectively. The binding affinity of amelogenin to apatite was found to be in the descending order of rP172, rP148, and 13k. Analysis of our data suggests that, before its complete degradation during enamel maturation, stepwise processing of amelogenin by MMP-20 and then KLK4 reduces amelogenin-apatite interaction.


Improving the reuse of computational models through version control.
Only models that are accessible to researchers can be reused. As computational models evolve over time, a number of different but related versions of a model exist. Consequently, tools are required to manage not only well-curated models but also their associated versions. In this work, we discuss conceptual requirements for model version control. Focusing on XML formats such as Systems Biology Markup Language and CellML, we present methods for the identification and explanation of differences and for the justification of changes between model versions. In consequence, researchers can reflect on these changes, which in turn have considerable value for the development of new models. The implementation of model version control will therefore foster the exploration of published models and increase their reusability.


Fundamentals of designing high-quality surveys: revisiting neonatal perinatal medicine survey applications.
Surveys in neonatal perinatal medicine are practical instruments for gathering information about medical practices, and outcomes related to the care of newborns and infants. This includes research for identifying needs, assessing requirements, analyzing the effects of change, creating policies, and developing curriculum initiatives. Surveys also provide useful data for enhancing the provision of healthcare services, assessing medical specialties, and evaluating training programs. However, creating a high-quality survey can be difficult for many practitioners, particularly when deciding how to formulate the right questions, whether to utilize various types of questions and how best to arrange or format the survey tool for effective responses. Problems with design principles have been evident in many surveys submitted for dissemination to the members of the Section of Neonatal Perinatal Medicine (SoNPM). To prevent potential measurement errors and increase the quality of surveys, it is crucial to follow a systematic approach in developing surveys by adhering to the principles of effective survey design. This review article provides a brief summary of survey use within the SoNPM, and offers guidance for creating high-quality surveys, including identifying important factors to consider in survey development and characteristics of well-written and effective questions. We briefly note techniques that optimize survey design for distribution through digital media.


Is Jaffe-Campanacci syndrome just a manifestation of neurofibromatosis type 1?
This article describes four patients with non-ossifying fibromas (NOFs) and multiple café-au-lait spots. Two of the patients were diagnosed with NOFs when they presented with a femur fracture. The other two patients were diagnosed with NOFs because of complaints of leg problems. In addition, axillary freckles and Lisch nodules were present in all four patients and multiple cutaneous neurofibromas in two patients. These four patients fulfilled the diagnostic criteria for neurofibromatosis type 1 (NF1) and also have been diagnosed with Jaffe-Campanacci syndrome. We propose that Jaffe-Campanacci syndrome is a manifestation of NF1 and suggest that patients with NF1 should have more rigorous radiographic screening of the long bones during early adolescence or adulthood to determine the presence or absence of NOFs. Appropriate intervention (exercise restriction, bracing, and/or surgery) might decrease the long-term disability associated with Jaffe-Campanacci syndrome.


3-[5-(4-Bromophenyl)-1H-pyrazol-3-ylamino]-5,5-dimethylcyclohex-2-en-1-one-(Z)-3-(4-bromophenyl)-3-chloroacrylonitrile (2/1): a stoichiometric cocrystal of a reaction product with one of its early precursors.
The title compound, 2C17H18BrN3O.C9H5BrClN, was crystallized from the reaction between 5,5-dimethylcyclohexane-1,3-dione, triethyl orthoformate and 5-amino-3-(4-bromophenyl)pyrazole, which had itself been prepared from the reaction between (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile and hydrazine. The compound is a stoichiometric 2:1 cocrystal of the reaction product 3-[5-(4-bromophenyl)-1H-pyrazol-3-ylamino]-5,5-dimethylcyclohex-2-en-1-one and the early reactant (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile. The two independent molecules of cyclohex-2-en-1-one are linked by N-H...N and N-H...O hydrogen bonds into complex bilayers and the molecules of acrylonitrile are trapped within large cavities in the substructure formed by the cyclohex-2-en-1-one molecules.


Wiring nanoscale biosensors with piezoelectric nanomechanical resonators.
Nanoscale integrated circuits and sensors will require methods for unobtrusive interconnection with the macroscopic world to fully realize their potential. We report on a nanoelectromechanical system that may present a solution to the wiring problem by enabling information from multisite sensors to be multiplexed onto a single output line. The basis for this method is a mechanical Fourier transform mediated by piezoelectrically coupled nanoscale resonators. Our technique allows sensitive, linear, and real-time measurement of electrical potentials from conceivably any voltage-sensitive device. With this method, we demonstrate the direct transduction of neuronal action potentials from an extracellular microelectrode. This approach to wiring nanoscale devices could lead to minimally invasive implantable sensors with thousands of channels for in vivo neuronal recording, medical diagnostics, and electrochemical sensing.


16S rDNA analyses of the cyanobacterial microbiota through the water-column in a boreal lake with a metalimnic Planktothrix population.
The Planktothrix population in Lake Steinsfjord has attracted particular attention, due to the potential development of toxic blooms. This population is special in the sense that mass developments of Planktothrix occur in the metalimnion. We investigated the distribution of Planktothrix, as well as other cyanobacteria, through the water-column during a Planktothrix mass development at 10-16 m depth. The analyses were done by chlorophyll measurements, microscopy, and by a recently developed 16S rDNA array-based method. These analyses showed that Planktothrix dominated the cyanobacterial community at 11 m, while cyanobacteria belonging to the order Nostocales were predominant at 4 m. The combination of analytical methods presented in this work provides a powerful tool to analyze cyanobacterial communities. We have developed a concept that enables both relative (16S rDNA array analyses) and absolute quantification (chlorophyll a measurements) of cyanobacteria through water-columns. Such approaches will be important in better understanding cyanobacterial microbiota and bloom dynamics.


Effect of glucagon on plasma alanine and glutamine metabolism and hepatic gluconeogenesis in sheep.
Net hepatic uptakes of plasma alanine (Ala), glutamate (Glu), and glutamine (Gln) were measured before and during intraportal glucagon infusions in five normaland four insulin-and alloxan-treated (ITA), conscious, fed sheep. Since hyperinsulinemia is associated with glucagon administration, ITA sheep were used so that constant plasma insulin levels could be maintained. Glucose turnover was determined by a vena caval infusion of glucose-6-'3H. In addition, in ITA sheep, Ala-'14C wasinfused for measurement of plasma Ala turnover, its unidirectional organ metabolism, and contribution to glucose synthesis. During infusion of glucagon, the net hepatic uptake of Ala increased significantly (P is less than 0.01) from control values of 3.8 plus or minus 0.5 and 2.7 plus or minus 0.6 mmol/h to 5.9 plus or minus 1.0 and 5.5 plus or minus 0.8 mmol/h in normal and ITA sheep, respectively. Similarly, Gin uptake increased from 4.3 plus or minus 1.4 and 1.6 plus or minus 0.5 to 5.5 plus or minus1.6 and 3.7 plus or minus 1.0 mmol/h, respectively. The conversion of Ala to glucose increased from control values of 1.7 plus or minus 0.5 to 3.0 plus or minus 0.5 mmol/h. Arterial plasma Ala and Gin concentrations decreased about 25% during glucagon administration, presumably as a result of their increased hepatic uptakes. A decreasein utilization of plasma Ala, but no change in production was calculated for the nonhepatic tissues, indicating that glucagon increased gluconeogenesis from Ala at the expense of muscle protein synthesis. Glucagon thus has a direct effect on the liver butonly an indirect effect on other tissues.


Formulation and evaluation of clarithromycin microspheres for eradication of Helicobacter pylori.
The objective of the study was to develop a stomach-specific drug delivery system for controlled release of clarithromycin for eradication of Helicobacter pylori (H. pylori). Floating-bioadhesive microspheres of clarithromycin (FBMC) were prepared by emulsification-solvent evaporation method using ethylcellulose as matrix polymer and Carbopol 934P as mucoadhesive polymer. The prepared microspheres were subjected to evaluation for particle size, incorporation efficiency, in vitro buoyancy, in vitro mucoadhesion and in vitro drug release characteristics. The prepared microspheres showed a strong mucoadhesive property with good buoyancy. The formulation variables like polymer concentration and drug concentration influenced the in vitro drug release significantly in simulated gastric fluid (pH. 2.0). The in vivo H. pylori clearance efficiency of prepared FBMC in reference to clarithromycin suspension following repeated oral administration to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. The FBMC showed a significant anti-H. pylori effect in the in vivo gerbil model. It was also noted that the required amount of clarithromycin for eradication of H. pylori was significantly less in FBMC than from corresponding clarithromycin suspension. The results further substantiated that FBMC improved the gastric stability of clarithromycin (due to entrapment within the microsphere) and eradicated H. pylori from the gastrointestinal tract more effectively than clarithromycin suspension because of the prolonged gastrointestinal residence time of the formulation.


A method for coronary bifurcation centerline reconstruction from angiographic images based on focalization optimization.
A method for the reconstruction of a vessel centerline from angiographic images is outlined in this work. A typical coronary artery segment with bifurcations was emulated with a 3D printed static phantom and several angiograms were acquired at various angular positions on the C-Arm. The effectiveness of the reconstruction turned out to be largely influenced by the intrinsic parameters of the angiographic system, particularly the homogeneous coordinates system scaling factor λ. Therefore, recourse was made to a heuristic optimization method to estimate the optimal value of λ for each view. We measured the reliability of the reconstruction method by varying the fitness function of the optimization step and measuring the distances of 8 test points in comparison to the corresponding points identified in the μCT centerline. Preliminary results showed that, with an adequate number of views, the adoption of the optimal fitness function allowed the median distance error to be decreased below the acceptance threshold of 10%. As expected, the reliability of the method is improved by increasing the number of processed views.


In vitro and in vivo assessment of hepatic and extrahepatic metabolism of diazepam in the rat.
Since diazepam is metabolized by many organs in the rat, the microsomal fractions of the liver, kidney, and lung from male Wistar rats were assayed for NADPH-dependent metabolism of diazepam and enzymatic parameters. The predicted extraction ratios were obtained from this in vitro experimental system. The organ clearances of the liver, kidney, and lung were then calculated for the determination of the relative contribution of each eliminating organ to the total body clearance (CLtot) of diazepam in the rat. The liver was the most effective eliminating organ, followed by the kidney and the lung, in that order. The hepatic extraction ratio of diazepam was determined in vivo after portal and femoral vein administrations of diazepam. The validity of the in vitro experimental system for the liver was demonstrated by a good agreement between the calculated hepatic extraction ratio of diazepam from in vitro enzymatic parameters (0.616) and that derived in vivo (0.648). However, the sum of organ clearances of the liver, kidney, and lung did not account for CLtot of diazepam in the rat, suggesting the possible contribution of the metabolism in the other organs or tissues, or an underestimation of the pulmonary and renal metabolism.


Full-Field Digital Mammography and Digital Breast Tomosynthesis.
Innovation in breast imaging techniques is leading to better breast cancer detection. Concurrently, breast cancer screening recommendations are changing, and breast density is becoming a more significant factor in breast cancer screening. Digital mammography has become the preferred screening method, with more breast imaging centers including the use of digital breast tomosynthesis (DBT). The technology's role in breast imaging has not been clarified fully, and several clinical trials are addressing DBT. This article presents research findings on digital mammography and DBT and explores the future role of 3-D breast imaging.


Regulatory role of interleukin-10 and interferon-gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum.
Schistosoma japonicum is the most pathogenic agent of hepatosplenic schistosomiasis. It causes fibrosis of the central (CentF) and peripheral (PerF) portal areas. We investigated whether CentF and PerF in Chinese fishermen infected with S. japonicum were associated with an abnormal production of cytokines and chemokines that, in experimental models, have been implicated in the regulation of fibrosis. Cytokines were measured by enzyme-linked immunosorbent assay in cultures of peripheral blood mononuclear cells from 127 patients, after stimulation with S. japonicum egg antigens. Data were analyzed by logistic regression that included age, sex, number of treatment episodes, alcohol use, and exposure as covariates. CentF was associated with low levels of interleukin (IL)-10 (P= .0004), regulated on activation normally T cell expressed and secreted (P= .0004), and macrophage inflammatory protein-1alpha (P= .007). In a multivariate analysis, only IL-10 was associated with CentF (odds ratio [OR], 10.8; 95% confidence interval [CI], 3.2-38; P= .0004). Splenomegaly was also associated with low IL-10 production and, independently, with CentF. In multivariate analysis, PerF was associated with low production of interferon (IFN)-gamma (OR, 8.2; 95% CI, 2-33; P= .0035) but not with production of IL-10. IL-10 is associated with protection against central fibrosis, because of its anti-inflammatory and antifibrosis effects. IFN-gamma is associated with protection against PerF, which depends more on egg load and egg-associated toxicity.


Interspecies communication and periodontal disease.
More than 500 bacterial strains may be found in dental plaque. In the beginning, the emphasis was laid on the isolation of bacteria in pure culture to define their properties. However, now, it has been well established that in nature the bacteria exist as a member of polymicrobial community or consortium of interacting species. Interactions among human oral bacteria are integral to the development and maturation of the plaque. These interactions occur at several levels including physical contact, metabolic exchange, small-signal molecule-mediated communication, and exchange of genetic material. This high level of interspecies interaction benefits the microorganism by providing a broader habitat range, effective metabolism, increasing the resistance to host defence, and enhancing their virulence. This generally has a detrimental effect on the host and is attributed to many chronic infections which poses a therapeutic challenge.


Validity of the assessment method of skeletal maturation by cervical vertebrae: a systematic review and meta-analysis.
To perform a systematic review with meta-analysis to answer the question: is the cervical vertebrae maturation index (CVMI) effective to replace hand-wrist radiograph (gold standard) in determining the pubertal growth spurt in patients undergoing bone growth? A search in three databases was performed, in which studies were selected that compared one of the two main assessment methods for cervical vertebrae (Hassel B, Farman AG. Skeletal maturation evaluation using cervical vertebrae. Am J Orthod Dentofacial Orthop 1995; 107: 58-66, or Baccetti T, Franchi L, McNamara JA Jr. An improved version of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth. Angle Orthod 2002; 72: 316-23) to a carpal assessment method. The main methodological data from each of the texts were collected and tabulated after. Later, the meta-analysis of the correlation coefficients obtained was performed. 19 articles were selected from an initial 206 articles collected. Regardless of the method used, the results of the meta-analysis showed that every article selected presented a positive correlation between skeletal maturation assessment performed by cervical vertebrae and carpal methods, with discrepancy of values between genders indicating higher correlation for the female gender (0.925; 0.878) than for the male (0.879; 0.842). When the assessment was performed without gender separation, correlation was significant (0.592; 0.688) but lower in the cases when genders were separated. With the results of this meta-analysis, it is safe to affirm that both CVMIs used in the present study are reliable to replace the hand-wrist radiograph in predicting the pubertal growth spurt, considering that the highest values were found in female samples, especially in the method by Hassel and Farman.


Nonribosomal synthesis of fengycin on an enzyme complex formed by fengycin synthetases.
Fengycin, a lipopeptidic antibiotic, is synthesized nonribosomally by five fengycin synthetases (FenC, FenD, FenE, FenA, and FenB) in Bacillus subtilis F29-3. This work demonstrates that these fengycin synthetases interlock to form a chain, which coils into a 14.5-nm structure. In this chain, fengycin synthetases are linked in the order FenC-FenD-FenE-FenA-FenB by interactions between the C-terminal region of an upstream enzyme and the N-terminal region of its downstream partner enzyme, with their amino acid activation modules arranged colinearly with the amino acids in fengycin. This work also reveals that fengycin is synthesized on this fengycin synthetase chain, explaining how fengycin is synthesized efficiently and accurately. The results from this investigation demonstrate that forming a peptide synthetase complex is crucial to nonribosomal peptide synthesis.


A High Performance LIA-Based Interface for Battery Powered Sensing Devices.
This paper proposes a battery-compatible electronic interface based on a general purpose lock-in amplifier (LIA) capable of recovering input signals up to the MHz range. The core is a novel ASIC fabricated in 1.8 V 0.18 µm CMOS technology, which contains a dual-phase analog lock-in amplifier consisting of carefully designed building blocks to allow configurability over a wide frequency range while maintaining low power consumption. It operates using square input signals. Hence, for battery-operated microcontrolled systems, where square reference and exciting signals can be generated by the embedded microcontroller, the system benefits from intrinsic advantages such as simplicity, versatility and reduction in power and size. Experimental results confirm the signal recovery capability with signal-to-noise power ratios down to -39 dB with relative errors below 0.07% up to 1 MHz. Furthermore, the system has been successfully tested measuring the response of a microcantilever-based resonant sensor, achieving similar results with better power-bandwidth trade-off compared to other LIAs based on commercial off-the-shelf (COTS) components and commercial LIA equipment.


Lymphocyte abnormalities in Aleutian disease virus infection of mink: decreased T lymphocyte responses and increased B lymphocyte levels in persistent viral infection.
Persistence of virus and a marked hypergammaglobulinemia are consistent features observed in mink with Aleutian disease virus infection. These events may result from altered lymphocyte function in infected mink. To test this possibility we determined the ability of lymphocytes from infected mink to respond to phytolectins (PHA and Con A), and a specific antigen (KLH) in a lymphocyte transformation test and quantitated the number of lymphocytes bearing surface immunoglobulin. Infected mink had a significantly lower response than normal mink to PHA and Con A (P less than 0.025), and the difference in the responses increased progressively with time post-infection. Infected mink immunized with KLH also had a decreased ability to respond to this antigen when compared to normal immunized mink (P less than 0.001). The number of lymphocytes bearing surface immunoglobulin was significantly elevated in three of 10 mink infected for 10 weeks, and in all of seven mink infected 32 weeks (P less than 0.001).


The Roles of Fractionated Potentials in Non-Macroreentrant Atrial Tachycardias Following Atrial Fibrillation Ablation: Recognition Beyond Three-Dimensional Mapping.
Non-macroreentrant atrial tachycardia (nAT) following atrial fibrillation (AF) ablation is being increasingly reported. Many issues remain to be elucidated. We aimed to characterize the fractionated potentials (FPs) in nAT and introduce a new method of cross-mapping for clarifying their roles. Forty-four nATs in 37 patients were enrolled and classified into focal AT (FAT, 12), microreentrant AT (MAT, 14), and small-loop-reentrant AT (SAT, 18) groups, according to activation pattern. FP was found on all targets except in nine FATs. The ratio of FP duration to AT cycle length (TCL) was different among groups (28 ± 7% in FAT, 53 ± 11% in MAT, and 42 ± 14% in SAT, p < 0.05), and ablation duration were longer in SATs (313 ± 298 vs. 111 ± 125 s, p < 0.05). The ratio of mappable cycle length to TCL was lower in the FAT group (63 ± 22% vs. 90 ± 9% and 89 ± 8%, p < 0.05). When cross-mapping was employed, trans-potential time differences in both longitudinal and transverse direction were longer around the culprit FP for MAT (p < 0.01). After Receiver Operating Characteristic curve analysis, it is best to adopt the sum of time difference ratios in both directions ≥60% as a cut-off value for discrimination of the FPs responsible for MAT with a sensitivity of 92% and specificity of 87%. FP could be found on target in most nATs following a previous AF ablation. The ratio of FP duration to TCL may help for differentiation. A simple method of cross-mapping could be employed to clarify the roles of FPs.


Site-directed mutational analysis of a membrane guanylate cyclase cDNA reveals the atrial natriuretic factor signaling site.
Natriuretic peptides are structurally related hormones that regulate hemodynamics of the physiological processes of diuresis, water balance, and blood pressure. One of the second messengers of these hormones is cGMP, and the type of receptor that is involved in the generation of cGMP is also a guanylate cyclase. Recent genetic evidence has revealed such a receptor family; two family members, GC-A and GC-B, have been cloned. We now describe the molecular cloning, sequencing, and expression of a cDNA clone from rat adrenal gland that encodes a membrane guanylate cyclase, GC alpha, that, with the exception of two amino acids, is structurally identical to GC-A and conforms to the purported topographical model of GC-A. The two amino acid changes are the substitutions Gln338----His338 and Leu364----Pro364, involving single nucleotide changes, CAG----CAC and CTG----CCG, respectively. Expression studies indicate that GC alpha cyclase activity is independent of the known natriuretic peptides, and direct binding studies demonstrate that GC alpha is not an ANF receptor. To determine the importance of Gln338 and Leu364 in ANF signaling, the GC alpha cDNA regions encoding amino acid residues 338 and 364 were remodeled by oligonucleotide-directed mutagenesis. A double mutant encoding Gln338 and Leu364, and a single-substitution mutant encoding Leu364 expressed both ANF binding and ANF-dependent cyclase activities, but the mutant encoding Gln338 and a deletion mutant lacking residue 364 did not express either of the above activities. These results define the critical role of Leu364 in ANF signal transduction.


Vaccination against murine cutaneous leishmaniasis by using Leishmania major antigen/liposomes. Optimization and assessment of the requirement for intravenous immunization.
Efficacy of vaccination against cutaneous leishmaniasis in highly susceptible BALB/c mice was assessed comparatively by using radiation-attenuated promastigotes and colloidal Ag mixtures generated from a mixed Leishmania major (LV39) isolate (SLV39) and from a virulent cloned line (SVJ2) derived from the Jericho 2 L. major isolate. Dehydration-rehydration vesicle (DRV) liposomes were used as adjuvants. In optimization experiments phospholipid composition of DRV was varied, and the distearoyl derivative (DSPC) (liquid-crystalline phase transition temperature (Tc) 54 degrees C) of egg lecithin L-alpha-phosphatidylcholine was found to be superior to the dipalmitoyl derivative (DPPC, Tc 41.5 degrees C) and underivatized L-alpha-phosphatidylcholine (Tc -10 degrees C). The criteria studied were in vivo priming for a secondary in vitro proliferative response and the prepatency of lesion onset after L. major challenge of mice immunized once i.v. A single s.c. immunization with SLV39 either free or entrapped within DSPC liposomes primed spleen cells to produce significant levels of IL-3 when stimulated with SLV39 in vitro. In contrast, the i.v. route of immunization with the same Ag preparations led to little or no IL-3 production by the spleen cells. Despite development of significant T cell activation, both SLV39 and SVJ2 administered s.c., either free or entrapped within liposomes, were not protective. However, i.v. immunization four times with SVJ2 entrapped within DSPC liposomes induced a level of resistance comparable with that of 2 x 10(7) gamma-irradiated promastigotes in the stringent BALB/c L. major model. Although significant, protection conferred after i.v. immunization with SLV39/DSPC liposomes was less effective. These data therefore show that DSPC/DRV liposomes, although a good adjuvant for inducing protective immunity to cutaneous leishmaniasis, are not able to overcome the requirement for an i.v. route of immunization with the leishmanial Ag preparation. Additionally, they demonstrate a correlation between IL-3 secretion and non-protection. They also suggest that SVJ2 represents a better source of protective Ag than SLV39.


Analysis of shear-induced and extensional-induced associating polymer assemblies: Brownian dynamics simulation.
In order to examine the difference between shear-induced and extensional-induced associating polymer assemblies at the molecular level, Brownian dynamics simulations with the bead-spring model were carried out for model DNA molecules with sticky spots. The radial distribution of molecules overestimates from that in the absence of flow and increases with increasing Weissenberg number in extensional flow, but slightly underestimates without regard to shear rate in shear flow. The fractional extension progresses more rapidly in extensional flow than in shear flow and the distribution of fractional extension at the formation time has a relatively sharper peak and narrower spectrum in extensional flow than in shear flow. In shear flow, the inducement of the assembly mainly results from the progress of the probability distribution of fractional extension. However, in extensional flow, the assembly is induced by both the progress of the probability distribution and increasing the values of the radial distribution.


Correction: Isoprene chain shuttling polymerisation between cis and trans regulating catalysts: straightforward access to a new material.
Correction for 'Isoprene chain shuttling polymerisation between cis and trans regulating catalysts: straightforward access to a new material' by Y. Phuphuak et al., Chem. Commun., 2017, 53, 5330-5333.


Bulbar paralysis in chronic alcoholism with recovery. A case report with discussion of possible etiologic factors.
A 47-year-old chronic alcoholic with acute onset of spastic bulbar paralysis and quadriparesis with recovery has been reported. The differential diagnosis of occurrence of bulbar symptoms in an alcoholic has been discussed. It is postulated that on anatomical and clinical grounds this case probably represents the occurrence of central pontine myelinolysis with recovery. Attention has been drawn to recent literature in which the importance of vascular insufficiency, hypotension and disturbance of fluid and electrolyte balance in the occurrence of irreversible myelinolytic lesions has been stressed. It is postulated that the recovery of this patient from a seemingly inexorably progressive lesion was the result of prompt reversal of etiologic factors which result in central pontine myelinolysis-like, fluid and electrolyte imbalance, hypotension and vascular insufficiency.


[MEASURING THE FUNCTIONAL IMPAIRMENT OF THE LUMBAR SPINE].
The purpose of our study was to outline the Hungarian validation process of the Oswestry Disability Index, the Quebec Back Pain Disability Scale, the Roland-Morris Disability Questionnaire and the Core Outcome Measurement Index, as well as to draw up recommendations regarding their future applications. The Hungarian versions were created after a cultural and linguistic adaptation. Next to the above-mentioned questionnaires, the questionnaire booklet used for validation also contained the WHOQoL-BREF general quality of life questionnaire and a pain measuring Visual Analog Scale. The data of low-back pain patients were registered twice in two weeks. We determined the internal homogeneity (Cronbach alpha), reproducibility, standard error of measurement and the minimal detectable change of the questionnaires. Patients were assigned into different two subgroups (surgical / non-surgical, with/without affection of nerve roots) and differences between the subgroups were examined with the help of the questionnaires. We determined the physical subscale of the WHOQoL-BREF and the correlation between the pain and the studied questionnaires. The value of Cronbach alpha was between 0.85 and 0.95. All four questionnaires showed significant differences (p<0.001) between the subgroups. The correlation studies brought strong and significant results (p<0.001, r>0.5) in every case. The values of reproducibility were between 0.93-0.92. The results of standard measurement error: 4.8 (Oswestry), 5.2 (Quebec), 1.6 (Roland-Morris), 0.59 (Core Index). The minimal detectable change was 13; 14; 4, and 2 points, respectively. The Hungarian versions of all four questionnaires are valid. They can be applied with scientific certainty to measure low back pain patients. From the studied questionnaires, we especially recommend the wide-raging application of the Oswestry Disability Index and the Core Outcome Measurement Index based on their psychometric and application features.


The clinical engineer: a ghost hunter or manager of EMI.
The management of EMI and risk control in the clinical environment presents the clinical engineer with new challenges and responsibilities. The keys to successfully meeting these challenges and responsibilities are education, cooperation, and the ability to be creative in the quest for solutions to problems of ever-increasing complexity. Experience in detecting and analyzing test results, which is gained over time, enhances the skills that clinical engineering professionals bring to this challenge. Attention to EMI risks has been influenced by a number of factors, including a spirit of cooperation between manufacturers and users, concerns over patient care and perceived product efficacy, and an increasing number of regulations by European and U.S. regulatory agencies. As a result, device emissions are being reduced and device immunity to EMI is improving. Further improvements in device immunity are still needed. The radio spectrum with regard to intentional radiators is in a continual state of flux. As industry attempts to improve labor efficiency through the use of radio communications, new and higher-powered sources of RF--both internal and external to the physical plant--appear each day in the clinical environment. Since the distance between intentional radiators and potentially susceptible devices is usually beyond the control of an institution, industry must continue to reduce device susceptibility. There should be a stronger dialogue between institutions (even if they do not have proactive EMI reduction programs) and manufacturers to identify ways to improve device immunity to EMI and to increase product designers' and users' awareness of potential problems.


Dual-color DNA-PAINT single-particle tracking enables extended studies of membrane protein interactions.
DNA-PAINT based single-particle tracking (DNA-PAINT-SPT) has recently significantly enhanced observation times in in vitro SPT experiments by overcoming the constraints of fluorophore photobleaching. However, with the reported implementation, only a single target can be imaged and the technique cannot be applied straight to live cell imaging. Here we report on leveraging this technique from a proof-of-principle implementation to a useful tool for the SPT community by introducing simultaneous live cell dual-color DNA-PAINT-SPT for quantifying protein dimerization and tracking proteins in living cell membranes, demonstrating its improved performance over single-dye SPT.


Global patterns in genomic diversity underpinning the evolution of insecticide resistance in the aphid crop pest Myzus persicae.
The aphid Myzus persicae is a destructive agricultural pest that displays an exceptional ability to develop resistance to both natural and synthetic insecticides. To investigate the evolution of resistance in this species we generated a chromosome-scale genome assembly and living panel of >110 fully sequenced globally sampled clonal lines. Our analyses reveal a remarkable diversity of resistance mutations segregating in global populations of M. persicae. We show that the emergence and spread of these mechanisms is influenced by host-plant associations, uncovering the widespread co-option of a host-plant adaptation that also offers resistance against synthetic insecticides. We identify both the repeated evolution of independent resistance mutations at the same locus, and multiple instances of the evolution of novel resistance mechanisms against key insecticides. Our findings provide fundamental insights into the genomic responses of global insect populations to strong selective forces, and hold practical relevance for the control of pests and parasites.


Musashi-1 regulates cell cycle and confers resistance to cisplatin treatment in Group 3/4 medulloblastomas cells.
Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 (MSI1) in Grp3 and Grp4-MBs. First, we assessed the expression profile of MSI1 in 59 primary MB samples (15-WNT, 18-SHH, 9-Grp3, and 17-Grp4 subgroups) by qRT-PCR. MSI1 mRNA expression levels were also validated in an additional public dataset of MBs (GSE85217). The ROC curve was used to validate the diagnostic standards of MSI1 expression. Next, the potential correlated cell-cycle genes were measured by RNA-Seq. Cell cycle, cell viability, and apoptosis were evaluated in a Grp3/Grp4 MB cell line after knockdown of MSI1 and cisplatin treatment. We identified an overexpression of MSI1 with a high accuracy to discriminate Grp3/Grp4-MBs from non-Grp3/Grp4-MBs. We identified that MSI1 knockdown not only triggered transcriptional changes in the cell-cycle pathway, but also affected G2/M phase in vitro, supporting the role of knockdown of MSI1 in cell-cycle arrest. Finally, MSI1 knockdown decreased cell viability and sensitized D283-Med cells to cisplatin treatment by enhancing cell apoptosis. Based on these findings, we suggest that MSI1 modulates cell-cycle progression and may play a role as biomarker for Grp3/Grp4-MBs. In addition, MSI1 knockdown combined with cisplatin may offer a potential strategy to be further explored in Grp3/Grp4-MBs.


[Study on the effects of the auricular acupuncture with different manipulations for rapid analgesia on the patients with lumbar disc hernia].
To compare the effects of the point-to-point needling and perpendicular needling of auricular acupuncture for rapid analgesia on the patients with lumbar disc hernia, and find which method is better for this disease. Ninety two patients were paired according to the three factors as sex, age and degree of pain, and then randomly divided into the point-to-point needling group and perpendicular needling group. The methods of point-to-point needling through the skin and perpendicular needling towardS the skin were respectively applied at bilateral lumbar areas as auricular acupuncture, and added acupoints following the change of symptom. All patients accorded with the demands of McGill pain questionnaire (MPQ), before treatment, 5 and 30 min after treatment, the accumulated score of pain was recorded respectively for observing the difference of the effects in both groups. After 5 min treatment, the effect of analgesia on the male patients in the point-to-point needling group was better than that of in the perpendicular needling group (P<0.05), but there was no difference on the female patients in both groups (P>0.05). After 30 min treatment, the effect of analgesia in the point-to-point needling group was better than that of the perpendicular needling group (P<0.05). Besides the patients with light degree pain, there was no significant difference between the two groups after 5 min treatment as score of pain (P>0.05), paired t-test showed that the effects of analgesia on the patients with lumbar disc hernia in the point-to-point needling group was better than that of perpendicular needling group (P<0.05). The point-to-point needling method can rapidly relieve patients' lumbar disc hernia of pain, which is better than the perpendicular needling method.


Hybrid nanoparticles for the topical delivery of norfloxacin for the effective treatment of bacterial infection produced after burn.
The present study was designed to investigate the solubility and penetrability of norfloxacin after the topical application of developed lipid-polymer hybrid nanoparticle (LPN) formulation. The core shell of the LPNs formulation was composed of poly (lactic-co-glycolic acid) that is highly lipophilic in nature, thus control the release of drug. The developed formulations were characterised for size, shape (transmission electron microscopy [TEM], scanning electron microscopy [SEM], and atomic force microscopy), entrapment efficiency, Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). Moreover, in vitro skin permeation studies were performed to determine release profile of the drug. Norfloxacin loaded nanoparticles retained there antimicrobial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa. Stability study was suggested that the suitable storage condition should be at 4 ± 2 °C/60 ± 5% RH for the LPNs. Therefore, these nanoparticles showed a safe and effective long-lasting approach for long treatment of bacterial infections due to burn.


MiR-200b regulates autophagy associated with chemoresistance in human lung adenocarcinoma.
Chemoresistance remains a major clinical problem in combating human lung adenocarcinoma (LAD), and abnormal autophagy is closely associated with this phenomenon. In the present study, an inverse correlation between miR-200b and autophagy-associated gene 12 (ATG12) expressions was observed in docetaxel-resistant (SPC-A1/DTX and H1299/DTX) and sensitive (SPC-A1 and H1299) LAD cells as well as in tissue samples. Further study showed that miR-200b directly targeted ATG12 in LAD. Moreover, miR-200b-dependent ATG12 downregulation inhibited autophagy and enhanced the chemosensitivity of SPC-A1/DTX and H1299/DTX cells both in vivo and in vitro. LAD chemoresistance is therefore closely related to downregulation of miR-200b and the corresponding upregulation of ATG12. These results provide new evidence for the mechanisms governing the microRNA (miRNA)-ATG12 network and their possible contribution to autophagy modulation and LAD chemoresistance.


Technetium-99m sestamibi scintigraphy and bone densitometry in primary hyperparathyroidism.
To review our recent experience with technetium-99m sestamibi scintigraphy in identification and localization of parathyroid adenomas and to determine bone mineral loss associated with primary hyperparathyroidism. Thirty-two double-phase technetium-99m sestamibi scans were obtained in 26 patients (22 female and 4 male patients; age range, 14 to 78 years). Serum calcium and intact parathyroid hormone concentrations were measured before scintigraphy. Histopathologic correlation was obtained in all patients who underwent a surgical procedure. Seventeen patients underwent bone densitometry studies of the lumbar spine and hip with use of dual-energy x-ray absorptiometry. Of the 32 scans, 17 (53%) were suggestive of a parathyroid adenoma ("positive"). In these patients, the mean serum calcium concentration was 2.68 mmol/L and the mean serum parathyroid hormone concentration was 669 pg/mL. Overall, one false-negative scan and one false-positive scan were encountered. The overall sensitivity for surgically proven detection and localization of parathyroid adenoma was 90%. The bone density measurements in patients with positive scans were substantially lower in the lumbar spine (mean T score, 2.9) and in the hip (mean T score, 2.1) in comparison with normal control subjects and significantly lower than in those with a negative scan (spine, P = 0.011; hip, P = 0.015). Double-phase technetium-99m sestamibi scintigraphy is highly sensitive and useful in detection and localization of parathyroid adenomas. Patients with primary hyperparathyroidism lose bone mineral from both cortical and cancellous bone sites.


The estimation of time varying dipoles on the basis of evoked potentials.
When a stimulus is presented to a subject, different cortical areas are activated simultaneously. These cortical sources are the generators of evoked potentials. The geometry parameters and the amplitude time course of each source can be estimated on the basis of EP data and the appropriate mathematical model. In the present paper, a model is proposed which describes EPs as the result of a set of stagnant dipoles, with time varying amplitude. It is shown how the parameter estimation problem can be solved efficiently. The method automatically solves the problem of separating overlapping components. A lower limit for the residual is derived, which can be used to determine the minimum number of sources required to describe observed responses adequately.


Implementation of a skilled nursing facility readmission review process.
30-day readmissions for patients at skilled nursing facilities (SNF) are common and preventable. We implemented a readmission review process for patients readmitted from two SNFs, involving an electronic review tool and monthly conferences. The electronic review tool captures information related to preventability and factors contributing to readmission. The study included 128 patients, readmitted within 30 days from 1 October 2015 through 1 May 2017, at a tertiary care academic medical centre in Boston, MA, and two partnering SNFs. There was a discrepancy in preventability rating between SNF and hospital reviewers, with 79.7% of cases rated not preventable by the SNF, and 58.6% by the hospital. There was moderate positive correlation between the hospital's and SNFs' preventability ratings (rs=0.652, p<0.001). In most cases, the SNF reviewers felt that no factors contributed (57.8%), and hospital reviewers felt that issues with end-of-life planning (14.1%) and medical complexity (12.5%) were major factors. Despite the lack of strong correlation between SNF and hospital responses, several cross-continuum quality improvement projects were developed. We found that implementation of a SNF readmission review process employing bidirectional review by SNF and hospital was feasible, and facilitated systems-based improvement in the transition from hospital to postacute care.


Online teaching strategies to improve collaboration among nursing students.
Collaborative problem-solving is an essential competency for nurses and all health professionals. This paper compares the design characteristics and educational benefits of three online-teaching strategies that nurse educators can use to build the critical thinking and social skills needed for effective collaboration: computer supported collaborative learning, case-based facilitated discussion, and cognitive flexibility hypermedia. These strategies support a critical instructional outcome required for effective collaboration: the ability to examine, assess, and synthesize multiple perspectives to resolve illstructured problems (i.e., problems for which there is no clear-cut solution). Descriptions, examples, and guidelines for implementing each strategy are provided. By integrating these strategies into their online courses, nurse educators can prepare nurses to work effectively with others to solve complex problems in clinical practice and the broader health-care system.


Contribution of RpoS to metabolic efficiency and ectoines synthesis during the osmo- and heat-stress response in the halophilic bacterium Chromohalobacter salexigens.
Chromohalobacter salexigens is a halophilic γ-proteobacterium that responds to osmotic and heat stresses by accumulating ectoine and hydroxyectoine respectively. Evolution has optimized its metabolism to support high production of ectoines. We analysed the effect of an rpoS mutation in C. salexigens metabolism and ectoines synthesis. In long-term adapted cells, the rpoS strain was osmosensitive but not thermosensitive and showed unaltered ectoines content, suggesting that RpoS regulates ectoine(s)-independent osmoadaptive mechanisms. RpoS is involved in the regulation of C. salexigens metabolic adaptation to stress, as early steps of glucose oxidation through the Entner-Doudoroff pathway were deregulated in the rpoS mutant, leading to improved metabolic efficiency at low salinity. Moreover, a reduced pyruvate (but not acetate) overflow was displayed by the rpoS strain at low salt, probably linked to a slowdown in gluconate production and/or subsequent metabolism. Interestingly, RpoS does not seem to be the main regulator triggering the immediate transcriptional response of ectoine synthesis to osmotic or thermal upshifts. However, it contributed to the expression of the ect genes in cells previously adapted to low or high salinity.


[Platelet-rich Plasma Induces M2 Macrophage Polarization via Regulating AMPK Singling Pathway].
To investigate the role of platelet-rich plasma (PRP) in inducing the M2 macrophage polarization via regulating AMPK singling pathway. The expressions of M1 marker CD11c and M2 marker CD206 in macrophages of blank control group, LPS group, LPS+PRP group, and LPS+PRP+Compound C group were detected by flow cytometry. Western blot was used to observe the effects of PRP on the expression of AMPK-mTOR signaling pathway-related proteins at different times (12 h, 18 h and 24 h) after LPS treatment. RNA interference technology was used to silence the expression of AMPK in macrophages, and the expression of TGF-β protein was subsequently examined by Western blot. LPS significantly reduced the expression of CD206 and increased the expression of CD11c (P <0.05). After the addition of PRP, the expression of CD206 was significantly increased (P <0.05), while the expression of CD11c was significantly decreased (P <0.05). Compared with LPS group, PRP treatment significantly increased the expressions of p-AMPK and p-ULK1 proteins at 12 h, 18 h and 24 h, while significantly decreased the expression of p-mTOR protein (P <0.05). After the addition of AMPK inhibitor Compound C, the expression of CD206 was significantly reduced (P <0.05) and the expression of CD11c was significantly increased compared with LPS+PRP group (P <0.05). After silencing the expression of AMPK in macrophages, the promotion effect of PRP on TGF-β was significantly reduced (P <0.05). PRP can stimulate the transformation of macrophages to M2 type via AMPK signalling pathway.


Trabeculectomy with ExPRESS: weighing the benefits and cost.
As glaucoma surgeons continue to search for an improvement over trabeculectomy, the ExPRESS miniature glaucoma shunt has gained interest as a possible contender. Peer-reviewed literature on ExPRESS is beginning to accumulate allowing an evidence-based review to assess the potential benefits and limitations compared to trabeculectomy. The current surgical procedure for ExPRESS implantation will be described followed by results of studies comparing ExPRESS to trabeculectomy, focusing on the following outcomes: success, intraocular pressure, and complications. Case reports of late complications specific to the ExPRESS device will be summarized. Finally, an economic analysis comparing ExPRESS to trabeculectomy will be provided as additional evidence to contribute to the decision matrix on deciding which filtration procedure to recommend. Despite a large number of ExPRESS implant procedures worldwide, there is a paucity of high-quality studies comparing ExPRESS to trabeculectomy. From the available literature to date the outcomes (success and early complications) of ExPRESS are similar to trabeculectomy. Reports of late complications related to device extrusion and malposition are beginning to be published; however, the significantly increased cost for ExPRESS surgery is likely to be the main limitation to widespread adoption of this procedure.


Clomiphene citrate does not adversely affect endometrial leukemia inhibitory factor levels.
The aim of this study was to compare endometrial leukemia inhibitory factor (LIF) levels in spontaneous and clomiphene citrate (CC)-induced cycles of patients with unexplained infertility. The patients were followed in two consecutive cycles. Endometrial samples were obtained 7 days after ultrasonographic evidence that ovulation has occurred during the spontaneous cycle, then the patients were induced with CC from day 5 to day 9 during the subsequent cycle with 50 mg/day, and ovulation monitoring and endometrial biopsy were performed in the same manner. The samples were obtained using a Pipelle biopsy device without using local anesthesia, and kept in formaldehyde solution until the day of measurement. Then they were homogenized in phosphate buffered distilled water, and LIF levels were detected in the homogenized fluid by ELISA method. Endometrial LIF levels were 470 +/- 52 and 501 +/- 45 pg/1 gram wet tissue in spontaneous and CC-induced cycles respectively, revealing no significant difference. Ovulation induction with CC did not adversely affect endometrial LIF levels.


Current impact of viral hepatitis on liver cancer development: The challenge remains.
Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.


Flagellar Propulsion of Sperm Cells Against a Time-Periodic Interaction Force.
Sperm cells undergo complex interactions with external environments, such as a solid-boundary, fluid flow, as well as other cells before arriving at the fertilization site. The interaction with the oviductal epithelium, as a site of sperm storage, is one type of cell-to-cell interaction that serves as a selection mechanism. Abnormal sperm cells with poor swimming performance, the major cause of male infertility, are filtered out by this selection mechanism. In this study, collinear bundles, consisting of two sperm cells, generate propulsive thrusts along opposite directions and allow to observe the influence of cell-to-cell interaction on flagellar wave-patterns. The developed elasto-hydrodynamic model demonstrates that steric and adhesive forces lead to highly symmetrical wave-pattern and reduce the bending amplitude of the propagating wave. It is measured that the free cells exhibit a mean flagellar curvature of 6.4 ± 3.5 rad mm-1 and a bending amplitude of 13.8 ± 2.8 rad mm-1 . After forming the collinear bundle, the mean flagellar curvature and bending amplitude are decreased to 1.8 ± 1.1 and 9.6 ± 1.4 rad mm-1 , respectively. This study presents consistent theoretical and experimental results important for understanding the adaptive behavior of sperm cells to the external time-periodic force encountered during sperm-egg interaction.


Identification of A/H5N1 influenza viruses using a single gene diagnostic microarray.
In previous work, a simple diagnostic DNA microarray that targeted only the matrix gene segment of influenza A (MChip) was developed and evaluated with patient samples. In this work, the analytical utility of the MChip for detection and subtyping of an emerging virus was evaluated with a diverse set of A/H5N1 influenza viruses. A total of 43 different highly pathogenic A/H5N1 viral isolates that were collected from diverse geographic locations, including Vietnam, Nigeria, Indonesia, and Kazakhstan, representing human, feline, and a variety of avian infections spanning the time period 2003-2006 were used in this study. A probabilistic artificial neural network was developed for automated microarray image interpretation through pattern recognition. The microarray assay and subsequent subtype assignment by the artificial neural network resulted in correct identification of 24 "unknown" A/H5N1 positive samples with no false positives. Analysis of a data set composed of A/H5N1, A/H3N2, and A/H1N1 positive samples and negative controls resulted in a clinical sensitivity of 97% and a clinical specificity of 100%.


Visible spatial contiguity of social information and reward affects social learning in brown capuchins (Sapajus apella) and children (Homo sapiens).
Animal social learning is typically studied experimentally by the presentation of artificial foraging tasks. Although productive, results are often variable even for the same species. We present and test the hypothesis that one cause of variation is that spatial distance between rewards and the means of reward release causes conflicts for participants' attentional focus. We investigated whether spatial contiguity between a visible reward and the means of release would affect behavioral responses that evidence social learning, testing 21 brown capuchins (Sapajus apella), a much-studied species with variant evidence for social learning, and one hundred eighty 2- to 4-year-old human children (Homo sapiens), a benchmark species known for a strong social learning disposition. Participants were presented with a novel transparent apparatus where a reward was either proximal or distal to a demonstrated means of releasing it. A distal reward location decreased attention toward the location of the demonstration and impaired subsequent success in gaining rewards. Generally, the capuchins produced the alternative method to that demonstrated, whereas children copied the method demonstrated, although a distal reward location reduced copying in younger children. We conclude that some design features in common social learning tasks may significantly degrade the evidence for social learning. We have demonstrated this for 2 different primates but suggest that it is a significant factor to control for in social learning research across all taxa. (PsycINFO Database Record