N-Heterocyclic carbene stabilized adducts of alkyl magnesium amide, bisalkyl magnesium and Grignard reagents: trapping oligomeric organo s-block fragments with NHCs.
Developing N-heterocyclic carbene (NHC) chemistry of simple organomagnesium compounds, this study reports the synthesis, X-ray crystallographic, and NMR spectroscopic characterization of three such new carbene complexes. The 1 : 1 alkyl magnesium amide : carbene complexes nBuMg(TMP)·IPr 1 and nBuMg(HMDS)·IPr 2 both exist as mononuclear complexes in the crystal but differ in solution as 2 remains intact whereas 1 undergoes a dynamic exchange involving partial decoordination of IPr [TMP is 2,2,6,6-tetramethylpiperidide; IPr is 1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene); HMDS is 1,1,1,3,3,3-hexamethyldisilazide]. Reaction of commercial nBu(2)Mg with IPr surprisingly produced the organoaluminium carbene complex nBu(3)Al·IPr, 3, which also forms a simple mononuclear structure in the crystal. The presence of the Al could be traced to the deliberate addition of a small quantity of Et(3)Al as a stabilizing agent in the commercial nBu(2)Mg reagent. Repeating this reaction with Al-free nBu(2)Mg afforded the hemisolvated carbene complex nBu(8)Mg(4)·2IPr, 4, the stoichiometry of which is dictated by its structure rather than by that used in the initial reaction mixture. The molecular structure of 4 is tetranuclear with a linear chain of 4 Mg centres bridged by nBu ligands and capped at each end by terminal nBu and IPr ligands. Synthesized by treating the Grignard reagent nBuMgCl with IPr, nBuMgCl·IPr, 5, forms a cyclodimer structure with chloro bridges and terminal nBu and IPr ligands.


Mouse aortic biomechanics are affected by short-term defective autophagy in vascular smooth muscle cells.
The physiology of vascular smooth muscle (VSMC) cells is affected by autophagy, a catabolic cellular mechanism responsible for nutrient recycling. Autophagy-inducing compounds may reverse arterial stiffening, whereas congenital VSMC-specific autophagy deficiency promotes arterial stiffening. The elevated aortic stiffness in 3.5-month-old C57Bl/6 mice, in which the essential autophagy-related gene Atg7 was specifically deleted in the VSMCs (Atg7F/F SM22α-Cre+ mice) was mainly due to passive aortic wall remodeling. The present study investigated whether aortic stiffness was also modulated by a shorter duration of autophagy deficiency. Therefore, aortic segments of 2-month-old Atg7F/F SM22α-Cre+ mice were studied. Similarly to the older mice, autophagy deficiency in VSMCs promoted aortic stiffening by elastin degradation and elastin breaks, and increased the expression of the calcium binding protein S100A4 (+ 157%), the aortic wall thickness (+ 27%), the sensitivity of the VSMCs to depolarization and the contribution of VGCC mediated Ca2+ influx to α1 adrenergic contractions. Hence, all these phenomena occurred before the age of 2 months. When compared to autophagy deficiency in VSMCs at 3.5 months, shorter term autophagy deficiency led to higher segment diameter at 80 mmHg (+ 7% versus - 2%), normal baseline tonus (versus increased), unchanged IP3-mediated phasic contractions (versus enhanced), and enhanced endothelial cell function (versus normal). Overall, and because in vivo cardiac parameters or aortic pulse wave velocity were not affected, these observations indicate that congenital autophagy deficiency in VSMCs of Atg7F/F SM22α-Cre+ mice initiates compensatory mechanisms to maintain circulatory homeostasis.


Imaging the inflammatory response to acute myocardial infarction in man using indium-111-labeled autologous platelets.
The feasibility of imaging the inflammatory response to acute transmural myocardial infarction in man using biologically active indium-111 (111In)-labeled autologous leukocytes was assessed in 36 patients. Indium-111 leukocytes (approximately 500 microCi) were injected i.v. 18-112 hours after the onset of chest pain. Cardiac imaging was performed 24 hours later with a mobile gamma camera. Twenty-one patients had positive images and 15 had negative images. The percent of positive images increased as the interval between infarction and 111In-leukocyte injection shortened; all patients injected within 24 hours of infarction had positive images. Patients with positive images were injected with 111In leukocytes earlier after infarction (mean +/- SEM, 43 +/- 4 vs 63 +/- 7 hours; p less than 0.05) and were younger (53 +/- 2 vs 65 +/- 3 years; p less than 0.05) than those with negative images. Several other parameters that could possibly have affected the imaging results were examined and were not significantly different in patients with positive and negative images. These included peak serum creatine kinase, location of infarction, incidence of pericarditis, use of antiinflammatory drugs (aspirin and indomethacin) or membrane-active antiarrhythmic drugs (lidocaine and procainamide), peripheral leukocyte count and cell labeling efficiency. The function of the labeled cell was similar in patients with positive and negative images. Six patients with acute infarction serving as controls and given free 111In oxine and six patients with stable coronary artery disease given 111In leukocytes all had negative cardiac images.


The role of lipid second messengers in aldosterone synthesis and secretion.
Second messengers are small rapidly diffusing molecules or ions that relay signals between receptors and effector proteins to produce a physiological effect. Lipid messengers constitute one of the four major classes of second messengers. The hydrolysis of two main classes of lipids, glycerophospholipids and sphingolipids, generate parallel profiles of lipid second messengers: phosphatidic acid (PA), diacylglycerol (DAG), and lysophosphatidic acid versus ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate, respectively. In this review, we examine the mechanisms by which these lipid second messengers modulate aldosterone production at multiple levels. Aldosterone is a mineralocorticoid hormone responsible for maintaining fluid volume, electrolyte balance, and blood pressure homeostasis. Primary aldosteronism is a frequent endocrine cause of secondary hypertension. A thorough understanding of the signaling events regulating aldosterone biosynthesis may lead to the identification of novel therapeutic targets. The cumulative evidence in this literature emphasizes the critical roles of PA, DAG, and sphingolipid metabolites in aldosterone synthesis and secretion. However, it also highlights the gaps in our knowledge, such as the preference for phospholipase D-generated PA or DAG, as well as the need for further investigation to elucidate the precise mechanisms by which these lipid second messengers regulate optimal aldosterone production.


Locality-Aware Crowd Counting.
Imbalanced data distribution in crowd counting datasets leads to severe under-estimation and over-estimation problems, which has been less investigated in existing works. In this paper, we tackle this challenging problem by proposing a simple but effective locality-based learning paradigm to produce generalizable features by alleviating sample bias. Our proposed method is locality-aware in two aspects. First, we introduce a locality-aware data partition (LADP) approach to group the training data into different bins via locality-sensitive hashing. As a result, a more balanced data batch is then constructed by LADP. To further reduce the training bias and enhance the collaboration with LADP, a new data augmentation method called locality-aware data augmentation (LADA) is proposed where the image patches are adaptively augmented based on the loss. The proposed method is independent of the backbone network architectures, and thus could be smoothly integrated with most existing deep crowd counting approaches in an end-to-end paradigm to boost their performance. We also demonstrate the versatility of the proposed method by applying it for adversarial defense. Extensive experiments verify the superiority of the proposed method over the state of the arts.


Character recognition from trajectory by recurrent spiking neural networks.
Spiking neural networks are biologically plausible and power-efficient on neuromorphic hardware, while recurrent neural networks have been proven to be efficient on time series data. However, how to use the recurrent property to improve the performance of spiking neural networks is still a problem. This paper proposes a recurrent spiking neural network for character recognition using trajectories. In the network, a new encoding method is designed, in which varying time ranges of input streams are used in different recurrent layers. This is able to improve the generalization ability of our model compared with general encoding methods. The experiments are conducted on four groups of the character data set from University of Edinburgh. The results show that our method can achieve a higher average recognition accuracy than existing methods.


Oxidized alpha 1-proteinase inhibitor: a fast-acting inhibitor of human pancreatic elastase.
Unlike human neutrophil elastase or porcine and rat pancreatic elastases, human pancreatic elastase is rapidly inhibited by oxidized alpha 1-proteinase inhibitor. The second-order association-rate constant for the reaction of the oxidized inhibitor with this enzyme (kass = 10(5) M-1 s-1) is only 8-fold lower than that measured with native alpha 1-proteinase inhibitor. Elastase releases faster from its complex with the oxidized inhibitor (t1/2 approximately 0.7 days) than from its complex with the native inhibitor (t1/2 approximately 5 days). Oxidized alpha 1-proteinase inhibitor is as efficient as the native inhibitor in inhibiting the elastolytic activity of elastase. Oxidized alpha 1-proteinase inhibitor may thus be considered as a physiological inhibitor of human pancreatic elastase which may prevent degradation of blood vessel elastin during acute hemorrhagic pancreatis.


Transcranial Direct Current Stimulation in Neuropathic Pain.
Neuropathic pain (NP) is one of the most common problems contributing to suffering and disability worldwide. Unfortunately, NP is also largely refractory to treatments, with a large number of patients continuing to report significant pain even when they are receiving recommended medications and physical therapy. Thus, there remains an urgent need for additional effective treatments. In recent years, nonpharmacologic brain stimulation techniques have emerged as potential therapeutic options. Many of these techniques and procedures - such as transcranial magnetic stimulation, spinal cord stimulation, deep brain stimulation, and motor cortical stimulation - have very limited availability, particularly in developing countries. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation procedure that has shown promise for effectively treating NP, and also has the potential to be widely available. This review describes tDCS and the tDCS procedures and principles that may be helpful for treating NP. The findings indicate that the analgesic benefits of tDCS can occur both during stimulation and beyond the time of stimulation. The mechanisms of cortical modulation by tDCS may involve various activities in neuronal networks such as increasing glutamine and glutamate under the stimulating electrode, effects on the μ-opioid receptor, and restoration of the defective intracortical inhibition. Additional research is needed to determine (1) the factors that may moderate the efficacy of tDCS, (2) the dose (e.g. number and frequency of treatment sessions) that results in the largest benefits and (3) the long-term effects of tDCS treatment.


Inhibitors of acyl-CoA:cholesterol acyltransferase. 5. Identification and structure-activity relationships of novel beta-ketoamides as hypocholesterolemic agents.
A study of structure-activity relationships of substituted beta-ketoamide ACAT inhibitors I and II was performed. The results of this study suggest that whereas the beta-keto group was tolerated with no loss in activity, beta-hydroxy and oxime moieties led to significantly reduced activity in vitro and in vivo. The most potent inhibitor from the acyclic series (I) (11, IC50 = 0.006 microM) contained a C-13 alkyl chain. This compound reduced plasma total cholesterol by 38% and 66% at 3 and 30 mg/kg, respectively, in cholesterol-fed rats. Dimethylation alpha to the anilide core (5) and subsequent N-methylation of the amide NH (6) decreased in vitro potency significantly. It was also found that high potency was retained with inhibitors which incorporated the carbonyl into a lactam ring (II).


Outcome of high-risk neonates with congenital complete heart block paced in the first 24 hours after birth.
Risk factors for poor outcome with congenital complete heart block include prematurity, low birth weight, hydrops, low ventricular rates, and congenital heart disease. In this group, medical therapy is often ineffective, pacing is technically challenging, and mortality exceeds 80%. The purpose of this study is to assess outcomes of patients with congenital complete heart block who were paced in the first 24 hours after birth owing to the presence of known risk factors. We performed a retrospective review of patients with congenital complete heart block paced in the first 24 hours after birth at our institution between November 1, 1995, and July 31, 2007. Thirteen patients were identified, 4 of whom had heterotaxy syndrome. Eleven patients had temporary epicardial pacing wires placed; 2 received permanent pacemakers as the initial mode of pacing. There were 7 deaths (54% mortality) at a mean age of 19.9 +/- 19 days. Among 7 patients with structural heart disease, there was 1 survivor. Among 6 patients with structurally normal hearts, there were 5 survivors (P = .025). Patients with temporary wires who survived to permanent pacemaker implantation (6/11) used their temporary leads for 33.8 +/- 18.3 days. In the severely affected fetus with congenital complete heart block and significant structural heart disease, outcomes remain poor; however, neonates with congenital complete heart block and structurally normal hearts who are monitored antenatally and delivered in a planned fashion at an institution capable of early pacing can have favorable outcomes. The use of temporary pacing wires is an option in the management of these patients.


The Impact of Contextual, Maternal and Prenatal Factors on Receptive Language in a Chilean Longitudinal Birth Cohort.
A secondary analysis was conducted on longitudinal data collected from ELPI, a representative Chilean survey to model Chilean infant's receptive language using contextual, maternal and prenatal factors. The sample for the current study comprised children aged between 36 and 48 months (n = 3921). The sample was re-assessed when children were aged 60-72 months (n = 3100). Linear regression analyses were conducted. At the first time point, all the predictors included were significant (living area, health system provision, maternal intelligence and education, adolescent pregnancy, maternal medical appointments during pregnancy, and presence of a significant other at childbirth), except for smoking during pregnancy. The model explained 13% of the variance. However, when timepoint one receptive language scores were included in the analyses for when children were aged 60-72 months, only two variables remained as significant predictors: previous receptive language scores and maternal education, explaining 21% of the variance. Findings and implications are discussed.


[Diagnosis of genetically determined diseases].
Enzymopathies of pyruvate kinase are caused by defects of structural genes forming stable and unstable mutants, respectively. Stable mutants of PK are characterized by high S0,5 PEP and nearly unchanged Vmax. A decrease of PEP affinity can be the result from a very high allosteric constant L0 or from an increased KPEP. From the pattern of PAGE can be concluded that stable PK mutants are tetraheteromers composed of two normal and two shortened polypeptide chains. We suppose that this is the result of a mutation of a codon which stops the polypeptide synthesis of PK earlier. Most PK mutants are unstable. They are characterized by low catalytic activity and high PEP affinity. The kinetic properties of unstable mutants are changed posttranslational by proteolytic modifications. Furthermore low S0,5 PEP values result from a persistence of the isoenzyme PK-K in reticulocytes and erythrocytes, respectively. A prenatal diagnosis of PK enzymopathies can be carried out with a very small blood volume by using the method of isoelectrophoretic focussing.


Upregulation of NRAMP1 mRNA confirms its role in enhanced host immunity in post-artificial infections of Salmonella enteritidis in chicks.
1. Salmonella enteritidis (SE) is reported as the most common food-borne pathogen transmitted through poultry products. The natural resistance-associated macrophage protein 1 (NRAMP1) is a candidate gene associated with SE-mediated immune response and is related to the phagocytosis of SE. In this study, the classical single-nucleotide polymorphism (SNP) G2357A in exon 8 of the NRAMP1 gene was detected. The expression of NRAMP1 mRNA was first investigated in heterophil granulocytes and spleen in chicks from two different Chinese native breeds at 1, 3 and 10 d post-infection. In addition, the association with the effect of SE challenge was identified. 2. The G2357A SNP showed no significant association with Salmonella natural infection in birds from two different Chinese native breeds. 3. The upregulation of NRAMP1 mRNA in heterophils and spleen was involved in the response to pathogenic SE colonisation during the acute infection period in chicks. The results suggest that genetics, age, gender and interactions among these factors play important roles in the modulation of NRAMP1 mRNA expression and copy number by SE-mediated immune response in different Chinese chickens. 4. In conclusion, the enhancement of host immunity mediated by the upregulation of NRAMP1 mRNA in heterophil granulocytes and spleen might be more obvious and earlier in the chicks resistant to infections with SE than in susceptible chicks.


The effects of aging on memory for sequentially presented objects in rats.
The current study investigated memory for sequentially presented objects in young rats 6 months old (n = 12) and aged rats 24 months old (n = 12). Rats were tested on a task involving three exploratory trials and one probe test. During the exploratory trials, the rat explored a set of three sequentially presented object pairs (A-A, B-B, and C-C) for 5 min per pair with a 3-min delay between each pair. Following the exploratory trials, a probe test was conducted where the rat was presented simultaneously with one object from the first exploratory trial (A) and one object from the third exploratory trial (C). Results from the exploratory trials showed no significant age-related differences in exploration, indicating that 24-month-old rats explored the object pairs as much as 6-month-old rats. The probe test demonstrated that 6-month-old rats spent significantly more time exploring object A compared to object C, indicating that young rats show intact temporal order memory for the exploratory trial objects. However, 24-month-old rats showed no preference for object A and spent a relatively equal amount of time exploring objects A and C. The results suggest that temporal order memory declines as a result of age-related changes in the rodent brain. The findings also may reflect differences in attraction to objects with different memory strengths. Since age-related differences were not detected during the exploratory trials, age-related differences on the probe trial were not due solely to decreased exploration, motivation, or locomotion.


Recyclable Magnetic Mesoporous Nanocomposite with Improved Sensing Performance toward Nitrite.
A magnetic nanomaterial for nitrite ion detection was demonstrated in the present study. This nanomaterial was prepared by grafting a rhodamine 6G derivative (denoted as Rh 6G-OH) into the channels of core-shell magnetic mesoporous silica nanospheres. The nanocomposite (denoted as Fe3O4@Rh 6G) showed large surface area and improved fluorescent performance to accumulate and recognize NO2(-), and its superparamagnetic behavior played an important role in reusability. The fluorescent intensity decreased linearly along with the NO2(-) concentration in the range of 1-50 μM, and the detection limit was estimated to be 0.8 μM, which was much lower than the maximum limit of nitrite ion in drinking water (65 μM) recommended by World Health Organization. Importantly, Fe3O4@Rh 6G could be magnetically collected and effectively reutilized after six test cycles.


The biophysical, molecular, and anatomical landscape of pigeon CRY4: A candidate light-based quantal magnetosensor.
The biophysical and molecular mechanisms that enable animals to detect magnetic fields are unknown. It has been proposed that birds have a light-dependent magnetic compass that relies on the formation of radical pairs within cryptochrome molecules. Using spectroscopic methods, we show that pigeon cryptochrome clCRY4 is photoreduced efficiently and forms long-lived spin-correlated radical pairs via a tetrad of tryptophan residues. We report that clCRY4 is broadly and stably expressed within the retina but enriched at synapses in the outer plexiform layer in a repetitive manner. A proteomic survey for retinal-specific clCRY4 interactors identified molecules that are involved in receptor signaling, including glutamate receptor-interacting protein 2, which colocalizes with clCRY4. Our data support a model whereby clCRY4 acts as an ultraviolet-blue photoreceptor and/or a light-dependent magnetosensor by modulating glutamatergic synapses between horizontal cells and cones.


[Social marketers' lack of success in using CSM discipline to harness commercial resources and increase contraceptive prevalence].
Social marketers have certainly shown that the CSM discipline can quickly and cost-effectively harness commercial resources to increase contraceptive prevalence. But why hasn't the social marketing idea caught on in more countries? According to Social Marketing Forum, only a tiny number of countries have active programs after more than a decade of effort. The most likely reason for this lack of success is doubt and fear on the part of both developing countries' officials and donor agencies about allowing marketing enthusiasts--with our very noticeable advertising methods--to join the family planning fight. And what has our answer been? Usually, a head-on retort such as, "But look at all the condoms we've sold]" And that gets us nowhere, because the successful peddling of 1 not-so-impressive method doesn't begin to balance the fears of a possible backlash that brash condom promotions could bring down on official heads. The lesson we should be learning is that social marketers possess to narrow an outlook and promote a small range of products that don't enthuse decisionmakers. Hence, we are often perceived as condom salesmen--and not much more. What should we be doing? We should be selling the idea of using private sector experience to assist national development. That means social development, particularly improved health, family planning and women's education. These 3 activities have proven effective in reducing fertility and would add up to a marketing opportunity--a longterm challenge that should enthuse dicisionmakers, private sector entrepreneurs and donor agencies alike. Further, our model--the commercial sector--is renowned for branching out and secceeding in a broad range of endeavors. As an example, Procter and Gamble uses separate divisions to market different products. Initiatives already exist in many countries to harness the private sector as a development tool. Social marketers should be leading the initiative--and benefitting from it, too.


Aroma effects of key volatile compounds in Keemun black tea at different grades: HS-SPME-GC-MS, sensory evaluation, and chemometrics.
The present study aimed to explore the relationship between the grade and the characteristic aroma in Keemun black tea (KBT). Headspace solid-phase microextraction (HS-SPME), gas chromatography-mass spectrometry (GC-MS), sensory evaluation, and chemometrics were employed to determine the changes in the flavor evolution of KBT at grade. The results showed that a total of 110 volatile components were identified. Linalool and linalool oxide were dominant. The orthogonal partial least squares discriminant analysis (OPLS-DA) combined with relative odor activity value (rOAV > 0.1) revealed that 11 volatile components were the key volatile compounds of KBT, such as benzeneacetaldehyde (rOAV: 3.43-5.96) and methyl salicylate (rOAV: 2.15 - 2.50). Furthermore, the partial least squares (PLS) model indicated that geraniol, linalool, and methyl salicylate benefited from the reservation of floral flavor of Keemun aroma characteristic of KBT. The findings presented in this thesis add to our understanding of KBT at different grades.


[Value of 16-slice spiral CT in the diagnosis of tumor-like bronchial tuberculosis].
To evaluate the value of 16-slice multi-detector CT (MDCT) in the diagnosis of tumor-like bronchial tuberculosis. Twenty-five patients with tumor-like bronchial tuberculosis underwent 16-slice CT scanning and the CT data were analyzed. Tumor-like bronchial tuberculosis were classified into 4 types according to the imaging features, namely intra-lumen nodule, intra-lumen mass, compression from outside of the bronchial lumens, and lung hilum mass. Tumor-like bronchial tuberculosis was featured by irregular bronchial wall thickening which led to decreased internal diameter of the bronchi with the external diameter remaining unchanged, ring-shaped enhancement, and absence of clear boundaries between the lesion and normal bronchi. 16-slice MDCT can be advantageous in displaying tumor-like bronchial tuberculosis, and axial scan with 16-slice spiral CT combined with image reconstruction allows detection of the lesions inside the trachea and bronchus.


Respiratory syncytial virus immune globulin treatment of RSV lower respiratory tract infection in previously healthy children.
To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). Infants and young children </=2 years of age with RSV LRI of </=4 days duration, and respiratory scores >/=2. 5 were enrolled. One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 </=85% at entry than did placebo recipients, but a higher proportion of placebo recipients required intensive care unit (ICU) care and mechanical ventilation at study entry. The mean RSV hospital stay was 5.52 +/- 0.69 days (SE) for placebo and 4.58 +/- 0.40 days for RSVIG. Additionally, there was an interaction between treatment group and entry respiratory score, which led to subgroup analysis. Children with modest respiratory illness did not receive any benefit from RSVIG therapy. RSVIG recipients with more severe illness (entry respiratory scores >/=3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.


[Hormonal induction of tyrosine aminotransferase and RNA synthesis in the cells of Morris hepatoma strain 7777].
The transfer of Morris hepatoma cells induced by the hormone within 10-60 min in to a hormone-free medium is associated with the augmentation of tyrosine aminotransferase synthesis. The kinetics of this process does not differ from that of the hormone-induced enzyme. The return of tyrosine aminotransferase synthesis to the basal level occurs 15-20 hours after the hormone withdrawal from the medium, although the concentration of the intranuclear hormone sharply decreases already after 3 hours. It was demonstrated that the presence in the hepatoma cell nuclei of 20-25% of the initially bound hormone for at least 20 hours after the cell transfer to the hormone-free medium is not sufficient for maintaining a high level of tyrosine aminotransferase gene expression. Using two-dimensional electrophoresis of 3H-labeled hepatoma cell proteins, it was demonstrated that the observed high activity of tyrosine aminotransferase is due to the de novo synthesis of enzyme molecules rather than to the existence of preformed long-living tyrosine aminotransferase molecules inside the cell. Study of [14C]uridine incorporation into non-ribosomal nuclear RNA of hepatoma cells showed a long-term presence of the label in the RNA throughout the chase experiment. It was assumed that the high activity of the enzyme for 10-15 hours after the hormone release from the hepatoma cell nuclei is due to the accumulation in the nuclei of long-living pre-mRNA molecules synthesized after the hormone addition to the cells and during the first hours after the cell transfer to the hormone-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)


Mondrian and the "boogie woogies": interruption of inner developmental logic or completion in old age?
Taking the work of the painter Piet Mondrian as a point of departure, artistic continuity and change are examined from a lifespan developmental perspective. It is argued that decontextualized continuity tends to occur within a given lifestage, whereas contextualized change is apt to emerge during a transition from one lifestage to another. Thus, Mondrian's gradual development of a unique style, predicated on logical, stage-like unfolding, is related to a midlife emphasis on formal structure. From a similar perspective, his dramatic shift away from this inner logic of development in his last work, the Boogie Woogies, is attributed to an ultimate effort in old age to synthesize art and reality, to reconcile a conflict between the laws of art and direct expression of sense experience.


The pathogenesis of pituitary tumors.
Recently there has been significant progress in our understanding of pituitary development, physiology, and pathology. New information has helped to clarify the classification of pituitary tumors. Epidemiologic analyses have identified a much higher incidence of pituitary tumors than previously thought. We review the pathogenetic factors that have been implicated in pituitary tumorigenesis and the application of novel targeted therapies that underscore the increasingly important role of the pathologist in determining accurate diagnoses and facilitating appropriate treatment of patients with these disorders.


Open-access liquid chromatography/mass spectrometry in a drug discovery environment.
The use of open-access mass spectrometry to monitor synthetic chemistry reactions, and also the integrity and purity of new chemical entities, has been a part of the medicinal chemist's tool-box for more than 5 years. Originally in our group at Wyeth Research there were two open-access methods available to the chemists, flow injection analysis (FIA) and liquid chromatography/mass spectrometry (LC/MS). The FIA method was approximately 3 min long, while the LC/MS method was approximately 20 min long (including an 8 min gradient). Within the first 2 years, the total number of open-access analyses increased by approximately 125%. It is interesting, however, that the number of LC/MS analyses increased by more than 285%. This is attributed to the fact that the chemists began using the LC/MS data to monitor reactions and also to check final product integrity and purity. In addition, the number of chemists performing parallel synthesis reactions has increased; thus, individual chemists can produce sample sets of up to 100 vials. This paper describes the implementation of new methodology, which accommodates the need for much faster run times and also the ability to acquire alternating positive and negative ion spectra within the same run. In addition, the instrument has been configured to e-mail the resulting processed data report to the submitting chemist. Several methods have been developed, including structure elucidation using in-source collision-induced dissociation (CID) and night-time analysis. The LC/MS methods for this system are described herein and are applicable to both industrial and academic synthetic chemistry optimization efforts.


[Resected prostate tissue volume and postoperative short-term outcomes of transurethral resection of the prostate].
To evaluate the influence of the resected prostate tissue volume (RPV) on the improvement of International Prostate Symptom Score (IPSS), quality of life (QOL), and voiding function after transurethral resection of the prostate (TURP). This study included 82 men with benign prostatic hyperplasia treated by TURP. Before and three months after TURP, we obtained the IPSS, QOL score, post-voiding residual urine volume (PVR), and maximum urinary flow rate (Qmax) from the patients. We measured the total prostate volume (TPV) and transition zone volume (TZV) by transrectal ultrasound preoperatively and investigate the influence of the RPV, RPV/TZV ratio, and RPV/TPV ratio on the efficiency of TURP. At three months after TURP, the mean Qmax increased by 9.27 ml/s, IPSS decreased by 15.86, QOL score increased by 3.47, PVR decreased by 87.1 ml, and 72.0% of the patients felt satisfied with the surgical results. There was no statistically significant difference in RPV between the patients satisfied and those dissatisfied with the results. Both the RPV/TPV and RPV/TZV ratios significantly increased in the satisfaction group as compared with the dissatisfaction group (P=0.002 and P=0.004). The areas under the ROC curve for the RPV/TPV and RPV/TZV ratios were 0.793 (P=0.001) and 0.687 (P=0.009), respectively. RPV is closely related to the short-term outcomes of TURP, and the ratios of RPV/TPV and RPV/TZV may be used as new markers to predict the outcomes of TURP.


Spatial Period of Laser-Induced Surface Nanoripples on PET Determines Escherichia coli Repellence.
Bacterial adhesion and biofilm formation on surfaces are associated with persistent microbial contamination, biofouling, and the emergence of resistance, thus, calling for new strategies to impede bacterial surface colonization. Using ns-UV laser treatment (wavelength 248 nm and a pulse duration of 20 ns), laser-induced periodic surface structures (LIPSS) featuring different sub-micrometric periods ranging from ~210 to ~610 nm were processed on commercial poly(ethylene terephthalate) (PET) foils. Bacterial adhesion tests revealed that these nanorippled surfaces exhibit a repellence for E. coli that decisively depends on the spatial periods of the LIPSS with the strongest reduction (~91%) in cell adhesion observed for LIPSS periods of 214 nm. Although chemical and structural analyses indicated a moderate laser-induced surface oxidation, a significant influence on the bacterial adhesion was ruled out. Scanning electron microscopy and additional biofilm studies using a pili-deficient E. coli TG1 strain revealed the role of extracellular appendages in the bacterial repellence observed here.


Effect of solvent polarity on the spectroscopic properties of an alkynyl gold(i) gelator. The particular case of water.
The spectroscopic properties of aggregates obtained from the hydrogelator [Au(4-pyridylethynyl)(PTA)] were studied in solvents of different polarities. Inspection of the absorption and emission spectra of diluted solutions showed that the singlet ground state of the monomeric species is sensitive to polarity and is stabilized in more polar solvents whereas the triplet excited state is rather insensitive to changes in polarity. The study of relatively concentrated solutions revealed the presence of new emission and excitation bands at 77 K that was attributed to the presence of different kinds of aggregates. Particularly interesting behaviour was revealed in water where aggregation is observed to be more efficient. For this, absorption, emission quantum yields and luminescence lifetimes of aqueous solutions at different concentrations were investigated in more detail. These data permitted one to correlate the increase of non-radiative and radiative rate constants of the low lying triplet emissive state with concentration, and therefore with the low limit concentration for aggregation, due to the shortening of the AuAu average distances in the aggregates and consequent enhancement of the spin-orbit coupling in the system.


Cefotaxime-hydrolysing activity of the beta-lactamase of Klebsiella oxytoca D488 could be related to a threonine residue at position 140.
The chromosomally encoded beta-lactamase of Klebsiella oxytoca D483 strain, active against all third-generation cephalosporins but ceftazidime, was purified to homogeneity. The pure protein was digested by trypsin, Staphylococcus aureus V8 protease or proteinase Asp-N. Amino acid sequences of the HPLC-separated proteolytic peptides were determined by manual Edman degradation. Overlapping fragments gave the alignment of the 263 residues of the beta-lactamase which presented 90% homology with the beta-lactamase of the K. oxytoca E23004 strain and about 40% homology with the other enzymes of the structural class A. The cefotaximase activity might result from interaction of a threonine residue at position 140 (position 165 in the numbering of Ambler) with the oxyimino group of the antibiotic.


[Robotic assistance in gynaecological surgery: State-of-the-art].
From the Automated Endoscopic System for Optimal Positioning (AESOP), a robotic arm which operates the laparoscope, to the robots Zeus and da Vinci, robotic assistance in gynaecological endoscopic surgery has continuously evolved for the last fifteen years or so. It has brought about new technical advancements: the last generation robots offer a steady three-dimensional image, improved instrument dexterity and precision, higher ergonomics and comfort for the surgeon. The da Vinci robotic system has been used without evincing any specific morbidity in various cases, notably for tubal reanastomosis, myomectomy, hysterectomy, pelvic and para-aortic lymphadenectomy or sacrocolpopexy amongst others. Robotic assistance in gynaecology is thus feasible. Like conventional laparoscopic surgery, it allows decreased blood loss and morbidity as well as shorter hospital stay, as compared to laparotomy. It might indeed allow many surgical teams to perform minimally invasive surgical procedures which they were not used to performing by laparoscopy. Randomized prospective studies are needed to define its indications more precisely. Besides, its medico-financial impact should be evaluated too.


Hypoglycemic effect of disopyramide in a case of diabetes mellitus under insulin treatment.
In a 41-year-old male with diabetes mellitus well controlled with insulin (50 units/day), hypoglycemia developed after starting disopyramide treatment (200 mg/day) for correction of tachycardia. Lower levels of blood glucose and smaller amounts of urinary sugar persisted until disopyramide was withdrawn even after reducing insulin to a minimum dose of 20 units/day. The insulin requirement increased again thereafter to the original dose. These results indicate that disopyramide had a hypoglycemic effect in this patient.


Incorporating VEGF-targeted therapy in advanced urothelial cancer.
Patients with relapsed or refractory urothelial carcinoma (UC) have poor prognosis coupled with few options for systemic treatment. The role of angiogenesis in the evolution of cancers has been established, and studies have shown that it plays a key role in the pathogenesis of UC. Many targeted agents have been used in phase I-II trials for the treatment of UC, with encouraging but modest results. Recently, studies combining angiogenesis inhibitors with other chemotherapeutic agents were able to achieve objective responses higher than most commonly used second-line therapies in UC. Future efforts in investigating these therapies in UC rely on identification of biomarkers and other predictors of response to anti-VEGF therapy.


Combined-evidence analyses of ultraconserved elements and morphological data: an empirical example in iguanian lizards.
Genomic datasets generated by next-generation sequencing are increasingly prevalent in phylogenetics, but morphological data are required to phylogenetically place fossils, corroborate molecular hypotheses and date phylogenies. Combined-evidence analyses provide an integrative assessment of tree topology. However, no attempt has been made to simultaneously analyse next-generation genomic datasets and morphological data, and the future of morphology in the context of genomic data is uncertain. I conducted combined-evidence analyses that include genomic and morphological datasets, specifically, with ultraconserved elements and two morphological matrices. In unweighted maximum-likelihood and Bayesian combined-evidence analyses, morphological signal was dwarfed by the ultraconserved elements, and some node support values were reduced relative to ultraconserved element-only analyses. Increasing the weight of morphological characters allowed those data to influence the tree, but weighting subjectivity should be considered in future analyses. More attempts should be made to simultaneously analyse genomic and morphological datasets.


Comparison of copper intrauterine device with levonorgestrel-bearing intrauterine system for post-abortion contraception.
The aim of this study was to compare the safety, bleeding pattern, effects, side-effects, complications and 6-month continuity rates of levonorgestrel-bearing intrauterine system (LNG-IUS) with conventional copper intrauterine device (Cu-IUD) inserted immediately after voluntary termination of pregnancy up to 10 weeks of gestation. One hundred women who underwent voluntary pregnancy termination and preferred IUD insertion as a contraceptive method after counseling were enrolled. The patients were randomly allocated to Cu-IUD or LNG-IUS and followed up at 10 days, and at 1, 3 and 6 months. The expulsion rates, continuation rates, side-effects, and bleeding patterns were compared. Fifty women in the Cu-IUD group and 44 women in the LNG-IUS group were followed up. The continuity and expulsion rate for Cu-IUD and LNG-IUS at the end of 6 months was 74%, 12%, and 75%, 11.3%, respectively. In LNG-IUS users, the incidence of amenorrhea and the number of spotting days were higher and hemoglobin increased throughout the follow-up period. The side-effects related to both methods were not different from interval insertions. Immediate post-abortion intrauterine contraception with Cu-IUD or LNG-IUS is a safe, reliable method. The incidence of side-effects is similar, and there is only a slightly higher rate of expulsion but an acceptable rate of method continuation.


A comparison of computed tomography, X-ray and Lodox® scans in assessing pediatric skull fractures using piglets.
Skull fractures are common in children both due to abuse and accidental incidences. The accurate detection of these fractures may therefore be critical. The aim of this study was to investigate the reliability of CT, X-ray, and Lodox® scans, the latter which has not previously been evaluated and is commonly employed in South Africa, in detecting the number, location and type of pediatric skull fractures. Blunt force trauma was inflicted with a mallet on ten piglet skulls, which were CT, X-ray, and Lodox® scanned and then macerated. The number, location, and type of skull fractures visible using each imaging modality, and on the cleaned skulls, were recorded. Sensitivities and specificities of each method were calculated. For fracture number and location, CTs had a sensitivity of 47.3%, X-rays 22.4% and Lodox® 23.3%. For fracture type, sensitivities were 46.1%, 16.6%, and 17.8% for CT, X-ray, and Lodox® , respectively. Specificities were high (92.5%-100%) which reduces the risk of incorrectly diagnosing fractures. However, low sensitivities increase the risk of failing to identify fractures and possible victims of abuse. Osteological analysis should preferably be the method of choice when evaluating pediatric skull trauma, and CTs should be used when osteological analysis is not feasible. If CT scanners are not available, X-rays and Lodox® may have to be used. In these cases, additional radiographic views of the skull are imperative and may increase the sensitivity of these methods, although they are not recommended to detect exact pediatric skull fracture number, location, and type.


Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition.
Lack of mechanical load leads to skeletal muscle atrophy, and one major underlying mechanism involves the myostatin pathway that negatively regulates protein synthesis and also activates Atrogin-1/MAFbx and MuRF1 genes. In hindlimb immobilization, leucine was observed to attenuate the upregulation of the referred atrogenes, thereby shortening the impact on fiber cross-sectional area, nonetheless, the possible connection with myostatin is still elusive. This study sought to verify the impact of leucine supplementation on myostatin expression. Male Wistar rats were supplemented with leucine and hindlimb immobilized for 3 and 7 days, after which soleus muscles were removed for morphometric measurements and analyzed for gene and protein expression by real-time PCR and Western blotting, respectively. Muscle wasting was prominent 7 days after immobilization, as expected, leucine feeding mitigated this effect. Atrogin-1/MAFbx gene expression was upregulated only after 3 days of immobilization, and this effect was attenuated by leucine supplementation. Atrogin-1/MAFbx protein levels were elevated after 7 days of immobilization, which leucine supplementation was not able to lessen. On the other hand, myostatin gene expression was upregulated in immobilization for 3 and 7 days, which returned to normal levels after leucine supplementation. Myostatin protein levels followed gene expression at a 3-day time point only. Follistatin gene expression was upregulated during immobilization and accentuated by leucine after 3 days of supplementation. Concerning protein expression, follistatin was not altered neither by immobilization nor in immobilized animals treated with leucine. In conclusion, leucine protects against skeletal muscle mass loss during disuse, and the underlying molecular mechanisms appear to involve myostatin inhibition and Atrogin-1 normalization independently of follistatin signaling.


Nickel-oxido structure of a water-oxidizing catalyst film.
The atomic structure of an electrodeposited Ni catalyst film is dominated by extensive di-μ-oxido bridging between Ni(III/IV) ions, as revealed by X-ray absorption spectroscopy. The structure is surprisingly similar to that of an analogous Co-based film and colloidal Mn-based catalysts. Structural requirements for water oxidation are discussed.


Expression of endothelin-1 and its receptors in the lungs of broiler chickens exposed to high-altitude hypoxia.
To investigate the influence of exposure to high-altitude (HA) hypoxia on the expressions of endothelin-1 (ET-1), endothelin type A (ETA) and endothelin type B (ETB) receptors in broiler chickens, immunohistochemistry studies were performed in the lungs. Six hundred 1-day-old male broiler chickens were randomly divided into two groups: group A, birds maintained under rich oxygen conditions (oxygen content 21%); and group B, birds exposed to HA hypoxia (oxygen content 13%). Our data showed that exposure to altitude elevated ET-1 and ETA gene expressions at 21 and 28 days of age when compared with the rich oxygen group. Meanwhile, a marked decline in ETB expression was observed at 28 days of age in the course of HA, although there were no significant changes (P>0.05) at 7, 14 and 21 days of age. The increased response was accompanied by adverse effects on weekly body weight gain and ascites mortality. These observations suggested that ET-1, ETA and ETB genes are normally expressed in the lungs of birds. Increased levels of ET-1 and ETA and decreased ETB gene expression in the lungs are probably involved in the lung dysfunction of broiler chickens with developmental ascites.


Glycogen synthase kinase-3β inhibitor SB216763 promotes DNA repair in ischemic retinal neurons.
Glycogen synthase kinase-3β (GSK-3β) has been shown to attenuate DNA damage in nerve cells, thereby enhancing neuronal survival under pathological conditions; however, the underlying mechanism remains unclear. An in vitro serum-starvation retinal neuron model and in vivo ischemia/reperfusion retina injury rat model were established and treated with SB216763, a GSK-3β inhibitor. SB21673 decreased the formation of γ-H2A histone family member X foci and enhanced the viability of ischemic retinal neurons. In addition, SB216763 upregulated expression of phosphorylated-CREB1, a ligase IV transcription factor, and significantly increased the transcriptional activity of ligase IV in ischemic retinal neurons. These results were confirmed in rat retinas following ischemia/reperfusion injury. Furthermore, we found that unlike lithium chlorine (a well-known direct inhibitor of GSK-3β), SB216763 inhibited GSK-3β activity by suppressing its phosphorylation. Taken together, our results suggest that GSK-3β inhibition enhances repair of DNA double-strand breaks by upregulating ligase IV expression in ischemic retinal neurons. This study was approved by the Institutional Animal Care and Use Committee of Zhongshan Ophthalmic Center on February 18, 2018.


Developmental aspects of renal beta-amino acid transport. IV. Brush border membrane response to altered intake of sulfur amino acids.
Taurinuria is characteristic of the immature rat. The capacity of the kidney to accumulate the beta-amino acid taurine and D-glucose was examined using isolated brush border membrane vesicles (BBMV) prepared from 28-day-old rats. Taurine accumulation was inversely proportional to osmolarity, indicating uptake rather than binding, and taurine accumulation was Na+-dependent. BBMV from 28-day rats did not accumulate D-glucose to the same degree as in adult BBMV, and the initial rate of uptake was slower. Taurine uptake had a similar Km and Vmax in BBMV from immature rats. Despite similarities in the kinetics of taurine uptake, higher urinary taurine concentrations are found in younger rats, suggesting that other factors, such as an efflux block, account for the taurinuria of young animals. A diet low in methionine and taurine (LTD) given for 7 days resulted in a lower excretion and fractional excretion of taurine than in animals fed a normal sulfur amino acid diet (NTD). A high taurine diet (HTD) causes excessive taurinuria. These patterns of excretion are reflected at the brush border membrane surface with greater uptake after the LTD and reduced uptake after the HTD. A kinetic analysis of adult and 28-day-old animal BBMV reveals that the Vmax of accumulation is altered by diet, whereas the Km remains unchanged. The Vmax is higher in BBMV from LTD animals and lower in BBMV from HTD animals. The kinetics of uptake are similar in adult and 28-day-old rat vesicles on a given diet. Thus, in addition to ontogenic changes in taurine excretion, there is an adaptive response to dietary alteration present at the brush border surface.


Effect of ABCB1 rs12720464 and rs1055302 polymorphisms in Chinese patients on the time course of action of rocuronium administered as a single dose.
To determine whether ABCB1 gene polymorphisms affect the time course of action of rocuronium in Chinese patients. This study included 105 unrelated Chinese patients undergoing general anesthesia with propofol, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Patients were allowed to recover spontaneously from the neuromuscular block. The time interval between the first maximum depression of the train of four (TOF) and spontaneous recovery TOF ratio of 0.25/0.7/0.8/0.9 was recorded. The Sequenom MassArray® single-nucleotide polymorphism (SNP) detection technology was used to detect the genotypes of the ABCB1 rs12720464, rs1055302. Demographic and non-genetic clinical data were also collected. In the present study, the mean time to spontaneous recovery of TOF ratio 0.8/0.9 in ABCB1 rs12720464 GG genotype was longer compared to that observed in ABCB1 rs12720464 AG genotype (56.77 ± 14.23 minutes vs. 49.50 ± 10.49 minutes, and 62.58 ± 18.16 minutes vs. 53.20 ± 12.56 minutes, respectively, p < 0.05). Further, the time to spontaneous recovery of TOF 0.7/0.8/0.9 in ABCB1 rs1055302 GG genotype was longer than that in ABCB1 rs1055302 AG genotype (52.00 ± 12.10 minutes vs. 44.83 ± 7.38 minutes, 55.96 ± 13.92 minutes vs. 46.83 ± 7.67 minutes, 61.66 ± 17.70 minutes vs. 49.50 ± 8.44 minutes, respectively, p < 0.05). In Chinese patients who were administered a single dose of rocuronium, the genetic variants ABCB1 rs12720464, and rs1055302 contribute to the individual< variability of time course of action.


Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium.
Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01-24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people.


Catheter-based treatment of ilio-femoral deep vein thrombosis - an update on current evidence.
Ilio-femoral deep vein thrombosis (DVT) has a high rate of long-term morbidity in the form of the postthrombotic syndrome (PTS). Therefore, management of acute thrombosis should not only focus on the prevention of acute complications such as propagation or embolisation of the initial clot but also on preventing PTS and recurrent thrombosis. Contemporary catheter-based treatments of deep vein thrombosis have proven to be safe and effective in selected patients. Current guidelines recommend medical therapy with anticoagulation alone for all but the most severe, limb-threatening thrombosis. They additionally allow for consideration of catheter-based treatment in patients with acute DVT and low risk of bleeding complications to prevent PTS. Recent studies favoring interventional therapy have not been included in these guidelines. Data on long-term outcome is expected to be published soon, clarifying and very likely strengthening the role of catheter-based treatments in the management of acute ilio-femoral DVT.


Concomitant expression of far upstream element (FUSE) binding protein (FBP) interacting repressor (FIR) and its splice variants induce migration and invasion of non-small cell lung cancer (NSCLC) cells.
Transcription factors integrate a variety of oncogenic input information, facilitate tumour growth and cell dissemination, and therefore represent promising therapeutic target structures. Because over-expression of DNA-interacting far upstream element binding protein (FBP) supports non-small cell lung cancer (NSCLC) migration, we asked whether its repressor, FBP-interacting repressor (FIR) is functionally inactivated and how FIR might affect NSCLC cell biology. Different FIR splice variants were highly expressed in the majority of NSCLCs, with the highest levels in tumours carrying genomic gains of chromosome 8q24.3, which contained the FIR gene locus. Nuclear FIR expression was significantly enriched at the invasion front of primary NSCLCs, but this did not correlate with tumour cell proliferation. FIR accumulation was associated with worse patient survival and tumour recurrence; in addition, FIR over-expression significantly correlated with lymph node metastasis in squamous cell carcinomas (SCCs). In vitro, we applied newly developed methods and modelling approaches for the quantitative and time-resolved description of the pro-migratory and pro-invasive capacities of SCC cells. siRNA-mediated silencing of all FIR variants significantly reduced the speed and directional movement of tumour cells in all phases of migration. Furthermore, sprouting efficiency and single cell invasiveness were diminished following FIR inhibition. Interestingly, the silencing of FIR isoforms lacking exon 2 (FIR(Δexon2)) alone was sufficient to reduce lateral migration and invasion. In summary, by using scale-spanning data derived from primary human tissues, quantitative cellular analyses and mathematical modelling, we have demonstrated that concomitant over-expression of FIR and its splice variants drives NSCLC migration and dissemination.


Here are key revisions to documentation guidelines.
ED reimbursement experts say the new documentation guidelines proposed by the Health Care Financing Administration will be easier to comply with. For a comprehensive history, only five organ systems are required to be reviewed, not 10. Instead of organ systems, the number of physical exam elements now includes individual components of those systems. It will be easier to identify the level of history if the patient is unable to give an adequate history.


Evaluation of immunogenicity and protective efficacy of orally delivered Shigella type III secretion system proteins IpaB and IpaD.
Shigella spp. are food- and water-borne pathogens that cause shigellosis, a severe diarrheal and dysenteric disease that is associated with a high morbidity and mortality in resource-poor countries. No licensed vaccine is available to prevent shigellosis. We have recently demonstrated that Shigella invasion plasmid antigens (Ipas), IpaB and IpaD, which are components of the bacterial type III secretion system (TTSS), can prevent infection in a mouse model of intranasal immunization and lethal pulmonary challenge. Because they are conserved across Shigella spp. and highly immunogenic, these proteins are excellent candidates for a cross-protective vaccine. Ideally, such a vaccine could be administered to humans orally to induce mucosal and systemic immunity. In this study, we investigated the immunogenicity and protective efficacy of Shigella IpaB and IpaD administered orally with a double mutant of the Escherichia coli heat labile toxin (dmLT) as a mucosal adjuvant. We characterized the immune responses induced by oral vs. intranasal immunization and the protective efficacy using a mouse pulmonary infection model. Serum IgG and fecal IgA against IpaB were induced after oral immunization. These responses, however, were lower than those obtained after intranasal immunization despite a 100-fold dosage increase. The level of protection induced by oral immunization with IpaB and IpaD was 40%, while intranasal immunization resulted in 90% protective efficacy. IpaB- and IpaD-specific IgA antibody-secreting cells in the lungs and spleen and T-cell-derived IL-2, IL-5, IL-17 and IL-10 were associated with protection. These results demonstrate the immunogenicity of orally administered IpaB and IpaD and support further studies in humans.


Virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization.
Virus-like particles were produced in insect cells containing either the L1 and L2 capsid proteins of bovine papillomavirus type 4 (BPV-4) or only the L1 protein. Both preparations of VLPs proved to be extremely effective prophylactic vaccines. Thirteen of 15 calves immunised with either L1-L2 VLPs or L1-VLPs were refractory to experimental challenge with high doses of BPV-4 and did not develop papillomas, while 9 of 10 control animals developed multiple oral papillomas. VLPs were not efficient as therapeutic vaccine in calves with established papillomas, although VLP-vaccinated animals appeared to undergo tumour regression more rapidly than nonvaccinated control animals. Antibody responses in VLP-vaccinated calves were associated with prevention of disease but not with regression of papillomas. Thus prophylactic VLP vaccination is effective in preventing disease in this model of mucosal papillomavirus infection. VLPs and native virus share at least some conformational epitopes, as shown by the cross-reactivity of their antibodies.


An experimental analysis of the contribution of 210Po and of 210Po produced by 210Pb decay to the gross alpha-particle activity of water samples.
The contribution of 210Po and of 210Po produced by 210Pb decay to the gross alpha-particle activity of water samples by U.S. Environmental Protection Agency Method 900.0 is investigated as a function of residue mass and geometry and time between sample collection and analysis. It is shown that these factors can cause the contribution to gross alpha-particle activity of 210Po to be up to 2.0 and 1.1 times the initial 210Po activity for grab and quarterly composite samples, respectively, and can cause the contribution to gross alpha-particle activity of 210Po from 210Pb decay to be up to 1.1 times and 1.5 times the 210Pb activity for grab and quarterly composite samples, respectively. It is also shown qualitatively that at least for some residues, there is a loss of polonium due to volatilization when the sample is heated over a flame.


Sex differences in how stress affects brain activity during face viewing.
Under stress, men tend to withdraw socially whereas women seek social support. This functional magnetic resonance imaging study indicates that stress also affects brain activity while viewing emotional faces differently for men and women. Fusiform face area response to faces was diminished by acute stress in men but increased by stress in women. Furthermore, among stressed men viewing angry faces, brain regions involved in interpreting and understanding others' emotions (the insula, temporal pole, and inferior frontal gyrus) showed reduced coordination with the fusiform face area and the amygdala, whereas the functional connectivity among these regions increased with stress for women. These findings suggest that stress influences emotional perception differently for men and women.


Vascular neurology nurse practitioner provision of telemedicine consultations.
Objective. The objective was to define and evaluate a role for the Vascular Neurology-Nurse Practitioner (VN-NP) in the delivery of telemedicine consultations in partnership with a vascular neurologist. Methods. Prospective stroke alert patients at participating hospitals underwent a two-way audio video telemedicine consultation with a VN-NP at a remotely located stroke center in partnership with a vascular neurologist. Demographic information, National Institutes of Health Stroke Scale (NIHSS) scores, diagnoses, CT contraindications to thrombolysis, thrombolysis eligibility, and time interval data were collected. The inter-rater agreement between VN-NP and vascular neurologist assessments was calculated. Results. Ten patients were evaluated. Four were determined to have ischemic stroke, one had a transient ischemic attack, two had intracerebral hemorrhages, and three were stroke mimics. Overall, three patients received thrombolysis. The inter-rater agreement between VN-NP and vascular neurologist assessments were excellent, ranging from 0.9 to 1.0. The duration of VN-NP consultation was 53.2 +/- 9.0 minutes, which included the vascular neurologist supervisory evaluation time of 12.0 +/- 9.6 minutes. Conclusion. This study illustrated that a stroke center VN-NP, in partnership with a vascular neurologist, could deliver timely telemedicine consultations, accurate diagnoses, and correct treatments in acute stroke patients who presented to remotely located rural emergency departments within a hub and spoke network. VN-NPs may fulfill the role of a telestroke provider.


Six-month survival and quality of life of intensive care patients with acute kidney injury.
Acute kidney injury (AKI) has high incidence among the critically ill and associates with dismal outcome. Not only the long-term survival, but also the quality of life (QOL) of patients with AKI is relevant due to substantial burden of care regarding these patients. We aimed to study the long-term outcome and QOL of patients with AKI treated in intensive care units. We conducted a predefined six-month follow-up of adult intensive care unit (ICU) patients from the prospective, observational, multi-centre FINNAKI study. We evaluated the QOL of survivors with the EuroQol (EQ-5D) questionnaire. We included all participating sites with at least 70% rate of QOL measurements in the analysis. Of the 1,568 study patients, 635 (40.5%, 95% confidence interval (CI) 38.0-43.0%) had AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of the 635 AKI patients, 224 (35.3%), as compared to 154/933 (16.5%) patients without AKI, died within six months. Of the 1,190 survivors, 959 (80.6%) answered the EQ-5D questionnaire at six months. The QOL (median with Interquartile range, IQR) measured with the EQ-5D index and compared to age- and sex-matched general population was: 0.676 (0.520-1.00) versus 0.826 (0.812-0.859) for AKI patients, and 0.690 (0.533-1.00) versus 0.845 (0.812-0.882) for patients without AKI (P <0.001 in both). The EQ-5D at the time of ICU admission was available for 774 (80.7%) of the six-month respondents. We detected a mean increase of 0.017 for non-AKI and of 0.024 for AKI patients in the EQ-5D index (P = 0.728). The EQ-5D visual analogue scores (median with IQR) of patients with AKI (70 (50-83)) and patients without AKI (75 (60-87)) were not different from the age- and sex-matched general population (69 (68-73) and 70 (68-77)). The health-related quality of life of patients with and without AKI was already lower on ICU admission than that of the age- and sex-matched general population, and did not change significantly during critical illness. Patients with and without AKI rate their subjective health to be as good as age and sex-matched general population despite statistically significantly lower QOL indexes measured by EQ-5D.


Two percent topical phenytoin sodium solution in treating pyoderma gangrenosum: a cohort study.
Oral phenytoin is an extensively used medicine for the treatment of convulsive disorders. Topical phenytoin has also been used for various types of ulcers. To determine the effectiveness of 2% topical phenytoin sodium solution in treating recalcitrant pyoderma gangrenosum. Six patients with treatment-resistant pyoderma gangrenosum who attended to Dermatology Unit/Ward were taken to the study and applied topical 2% phenytoin sodium solution to the wounds alone with other systemic therapy. Response to the treatment was assessed weekly. Three patients had idiopathic PG and other three had secondary diseases. At the end of the 4th week four patients showed complete resolution of the ulcers whereas other two patients showed the partial resolution. No adverse effects were noted. Phenytoin sodium 2% solution is beneficial for pyoderma gangrenosum (PG) with various etiologies. It enhanced the healing of the ulcer especially when the patient has treatment resistant disease.


Relaxation of sheep urethral muscle induced by electrical stimulation of nerves: involvement of nitric oxide.
Isolated smooth muscle preparations from the sheep urethra responded to electrical field stimulation with contraction when basal tension was low (5-6 mN), but with relaxation when the preparations were contracted with noradrenaline (NA), clonidine, or prostaglandin F2a. No relaxant response could be elicited in high K+ (124 mM) contracted preparations. Electrically induced relaxations had a threshold of less than 1 Hz and a maximum at 8 Hz. Both contractant and relaxant responses were abolished by tetrodotoxin, indicating that they were caused by transmitters released from nerves. The amplitude of the relaxant responses showed a highly significant correlation to the tension induced by noradrenaline. A coefficient (R/T) was calculated relating relaxation to noradrenaline-induced tension. In this way it is possible to separate the effect of drugs on muscle tension (non-specific effect) from their action on the electrically induced relaxation (specific effect). Chemical sympathectomy with 6-OHDA did not significantly modify the relaxant response to 6 Hz in noradrenaline contracted strips, as evaluated by the R/T coefficient. The electrically induced relaxation was not affected by hexamethonium, propranolol, phentolamine, muscarinic receptor blockade, cocaine, indomethacin, or methysergide. Both nifedipine and Bay K 8644 inhibited significantly the response induced by electrical stimulation, decreasing its maximum. Nifedipine, but not Bay K 8644, significantly reduced the level of tension induced by noradrenaline, and its effect, evaluated by the R/T coefficient, was an increase in the electrically induced relaxation, whereas Bay K 8644 had a significant inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)


Trait approach and avoidance motivation: lateralized neural activity associated with executive function.
Motivation and executive function are both necessary for the completion of goal-directed behavior. Research investigating the manner in which these processes interact is beginning to emerge and has implicated middle frontal gyrus (MFG) as a site of interaction for relevant neural mechanisms. However, this research has focused on state motivation, and it has not examined functional lateralization. The present study examined the impact of trait levels of approach and avoidance motivation on neural processes associated with executive function. Functional magnetic resonance imaging was conducted while participants performed a color-word Stroop task. Analyses identified brain regions in which trait approach and avoidance motivation (measured by questionnaires) moderated activation associated with executive control. Approach was hypothesized to be associated with left-lateralized MFG activation, whereas avoidance was hypothesized to be associated with right-lateralized MFG activation. Results supported both hypotheses. Present findings implicate areas of middle frontal gyrus in top-down control to guide behavior in accordance with motivational goals.


Berberine as a natural modulator of inflammatory signaling pathways in the immune system: Focus on NF-κB, JAK/STAT, and MAPK signaling pathways.
Three main inflammatory signaling pathways include nuclear factor-κB (NF-κB), Janus kinases/Signal transducer and activator of transcriptions (JAKs/STATs), and mitogen-activated protein kinases (MAPKs) play crucial roles in inducing, promoting, and regulating inflammatory responses in the immune system. Importantly, the breakdown of mechanisms that tightly regulate inflammatory signaling pathways can be the underlying cause of uncontrolled inflammatory responses and be associated with the generation and development of several inflammatory diseases. Hence, therapeutic strategies targeting inflammatory signaling pathways and their downstream components may promise to treat inflammatory diseases. Studies over the past two decades have provided important information on the polytrophic pharmacological and biochemical properties of berberine (BBR) as a naturally occurring compound, such as antioxidant, antitumor, antimicrobial, and antiinflammatory activates. Interestingly, the modulatory effects of BBR on inflammatory signaling cascades, which lead to the inhibition of inflammation, have been widely investigated in several in vitro and in vivo studies. For the first time, herein, this comprehensive review attempts to put together these studies and provide important insight into the modulatory effects of BBR on NF-κB, JAKs/STATs, and MAPKs signaling pathways in vitro in various types of immune cells and in vivo in several experimental inflammatory diseases. As the second achievement of this review, we also explore the therapeutic efficacy and antiinflammatory effects of BBR regarding its modulatory action.


Effect of insulin-like growth factor-1 on the responses to and recognition of hypoglycemia in humans. A comparison with insulin.
Recombinant human insulin-like growth factor-1 (rhIGF-1) lowers blood glucose in humans but its effect on counterregulatory responses has not been established. We therefore compared infusions of rhIGF-1 (0.7 micrograms/kg per min) and insulin (0.8 mU/kg.min) for 120 min in 10 healthy volunteers (glucose allowed to fall freely). With both, glucose fell rapidly because of stimulation of glucose uptake and suppression of hepatic glucose production. Despite similar plasma glucose nadirs (2.6 +/- 0.1 vs. 2.7 +/- 0.1 mM), the glucagon response was absent (P < 0.005), growth hormone release was attenuated (P < 0.03), and norepinephrine levels were increased (P < 0.05) by rhIGF-1 compared with insulin. Absent glucagon responses were associated with a blunting of the rebound increase in glucose production (P < 0.05 vs. insulin). After stopping the infusions, glucose recovery was delayed with rhIGF-1 (P < 0.001 vs. insulin). To further evaluate the effects of rhIGF-1 during a standard hypoglycemic stimulus, eight additional healthy subjects received rhIGF-1 or insulin while glucose was clamped at 2.8 mM. Again the rise in glucagon during insulin-induced hypoglycemia was totally abolished by rhIGF-1. Growth hormone responses were delayed, whereas increases in norepinephrine, heart rate, and symptomatic awareness of hypoglycemia were greater with rhIGF-1 compared with insulin (P < 0.05). It was concluded that rhIGF-1 suppression of glucagon release during hypoglycemia impairs glucose recovery. Paradoxically, awareness of hypoglycemia is enhanced with rhIGF-1 in part due to stimulation of the sympathetic activity.


Cloning and expression of the mouse PIP49 (Pancreatitis Induced Protein 49) mRNA which encodes a new putative transmembrane protein activated in the pancreas with acute pancreatitis.
We have used a microarray-based strategy to characterize, at the molecular level, the pancreatic emergency program set up by the pancreatic cells in response to pancreatitis. In this strategy, the phenotype of the pancreatitis-affected pancreas is established by characterization of a large number of its transcripts using a high-density mouse cDNA microarray. This method allows identification of transcripts differentially expressed during pancreatitis. We describe here the cloning, sequencing, and expression analysis of a new gene, named PIP49 (Pancreatitis Induced Protein 49). Its very strong expression is specific of acinar cells and occurs rapidly after initiation of the acute phase of pancreatitis. Analysis of its primary and secondary structures strongly suggests that PIP49 encodes a putative transmembrane protein.


Community influences on breast feeding.
The incidence of breast feeding in Camden and Paddington is reported for two periods, 1974-75 and 1976-77. In 1976 a programme was begun to encourage breast feeding by increasing contact and support by the health visitor and child health visitor and child health clinic antenatally and postnatally. Fifty-eight per cent of mothers in Camden and 56% of mothers in Paddington breast fed at 3 weeks in 1976-77 compared with 24% (Camden) and 20% (Paddington) in 1974-75. The incidence of breast feeding in the experimental areas was compared with that in a similar control area in which no intervention occurred to investigate whether this increase reflected a widespread increase in the popularity of breast feeding or resulted from intervention. In 1976-77 more mothers in the experimental, than in the control area who breast fed on discharge continued to do so during the first 5 months. Of the mothers who were discharged breast feeding 88% in Camden and 73% in Paddington compared with 57% in the control area were still doing so at 6 weeks. The pattern of home visiting by the health visitors and attendance at the child health clinic was also investigated. More antenatal and postnatal home visits, more clinic visits and earlier home visits took place in the experimental areas compared with the control area. We conclude that the health visitor and child health clinic have an important role to play in the management of lactation.


[Contemporary strategy and guideline of COPD therapy].
Actual treatment of COPD is not able to reduce and suppress the inflammation in small airways and lung parenchyma. For this reason the important target is an elimination of risk factors responsible for disease progress, that should be combined with patients education and smoking cessation. The role of viral and bacterial infections in exacerbations of COPD is well known. The guidelines of COPD therapy show that long acting beta2-agonists and cholinolytics are basic bronchial dilators, but glucocorticosteroids may be applied in III or IV stages of disease and only in patients with good response. At the end stage of COPD long-term oxygen therapy lung volume reduction surgery and lung transplantation should be considered.


Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower- Extremity Ulcers in Patients With Diabetes: Results of the DAMO2CLES Multicenter Randomized Clinical Trial.
Conflicting evidence exists on the effects of hyperbaric oxygen therapy (HBOT) in the treatment of chronic ischemic leg ulcers. The aim of this trial was to investigate whether additional HBOT would benefit patients with diabetes and ischemic leg ulcers. Patients with diabetes with an ischemic wound (n = 120) were randomized to standard care (SC) without or with HBOT (SC+HBOT). Primary outcomes were limb salvage and wound healing after 12 months, as well as time to wound healing. Other end points were amputation-free survival (AFS) and mortality. Both groups contained 60 patients. Limb salvage was achieved in 47 patients in the SC group vs. 53 patients in the SC+HBOT group (risk difference [RD] 10% [95% CI -4 to 23]). After 12 months, 28 index wounds were healed in the SC group vs. 30 in the SC+HBOT group (RD 3% [95% CI -14 to 21]). AFS was achieved in 41 patients in the SC group and 49 patients in the SC+HBOT group (RD 13% [95% CI -2 to 28]). In the SC+HBOT group, 21 patients (35%) were unable to complete the HBOT protocol as planned. Those who did had significantly fewer major amputations and higher AFS (RD for AFS 26% [95% CI 10-38]). Additional HBOT did not significantly improve complete wound healing or limb salvage in patients with diabetes and lower-limb ischemia.


A novel splice variant of fibroblast growth factor receptor 2 in human leukemia HL-60 cells.
Fibroblast growth factor receptors (FGFRs) genes have been shown to be translocated in multiple myeloma (MM) and myeloproliferative disorder (MPD), indicating an important role for the FGFRs in hematologic malignancies. Here, we describe a novel splice variant of FGFR2 (FGFR2AT-I) arising from skipping exons 7-10 in human myeloid leukemia HL-60 cells, encoding a FGFR2 in which the Ig-like-III domain is deleted while the remainder of the mature molecule is fused in-frame to the transmembrane and COOH-terminal cytoplasmic kinases. Binding assays demonstrated that the FGFR2AT-I was able to bind FGF1, FGF2, and FGF7, leading to loss of ligand binding specificity. Furthermore, overexpression of FGFR2AT-I resulted in increased AKT and MAPK activation, conferring a survival advantage. Taken together, these findings indicate that the dysregulation of FGFRs' function by aberrant mRNA splicing contributes to tumor progression.


[Periurethral collagen injections: results after 2 years in 25 patients with severe urinary incontinence].
To study the efficacy and safety of periurethral collagen injection in the treatment of severe urinary incontinence. From 1994 to 1998, 25 periurethral collagen injections were performed in 25 women with a mean age of 65 years presenting with urinary incontinence classified as grade III in 17 cases and grade II in 9 cases, under local anaesthesia in 5 cases, spinal anaesthesia in 10 cases and general anaesthesia in 10 cases. Twenty patients were treated for recurrent incontinence. One injection was performed in 20 cases and two injections were performed in 5 cases. None of the patients presented disorders of pelvic muscles. The preoperative urodynamic assessment did not reveal any cases of detrusor instability, and showed a mean urethral closure pressure of 35 cm H2O. A skin test was performed in each case at least 30 days before the injection. The mean hospital stay was 2.75 days. The mean quantity of collagen injected was 5.7 ml. With a mean follow-up of 24 months, 33% of patients were continent, 39% were improved and 28% were considered to be failures. No complications were observed. Due to its safety, this method can be proposed in outpatients with good results, in patients of all ages, either as first-line treatment or for recurrent incontinence, as, in the case of failure, this technique does not comprise subsequent treatment by another operation.


HLA-A, B, DR, and DQ antigens in black patients with severe chronic rheumatic heart disease.
To determine whether genetic factors could be involved in the pathogenesis of rheumatic heart disease, we performed HLA-A and HLA-B typing in 120 black patients with severe chronic rheumatic heart disease requiring cardiac surgery, and HLA-DR and HLA-DQ typing in 103 and 97 of these patients, respectively. The HLA typing was done by a standard microlymphocytotoxicity method. Patients were 12 to 60 years old (mean 27.6 +/- 14.5). No differences in HLA-A, HLA-B, and HLA-DQ frequencies between patients and controls were noted. HLA-DR 1 antigen was present in 12.6% of patients compared with 2.7% of normal control subjects (corrected p less than .045; relative risk = 5.2) and the HLA-DRw6 antigen was present in 31.1% of patients compared with 15% of control subjects (corrected p less than .045; relative risk = 2.6). These findings suggest that genetically determined immune-response factors may play a role in the pathogenesis of severe chronic rheumatic heart disease.


[Role of hypoxia-inducible factor-1alpha in the prevention of cardiomyocyte injury induced by hypoxic preconditioning].
In order to understand the intracellular mechanism of preconditioning, we investigated the relationship among activities of extracellular signal-regulated protein kinases (ERKs), the expression of hypoxia-inducible factor -1alpha (HIF-1alpha) and the effect of hypoxic preconditioning (HPC) on cell injury induced by hypoxia-reoxygenation in cultured neonatal rat cardiomyocytes 24 h after brief hypoxia. Cultured cardiomyocytes of neonatal Sprague-Dawley rats were divided into four groups: hypoxia/reoxygenation (H/R), hypoxia preconditioning (HPC), hypoxia preconditioning + mitogen-activated protein kinase (MAPK) inhibitor PD98059 (HPC+PD98059), and control (C). We measured the survival rate and apoptosis rate of cardiomyocytes at 6 or 12 h after hypoxia/reoxygenation, activities of extracellular signal-regulated protein kinases (ERKs), and expression of hypoxia-inducible factor-1alpha (HIF-1alpha). We found that the survival rate of cardiomyocytes in hypoxic preconditioning group increased by 6.08% and 7.91% at 6 and 12 h after hypoxia/reoxygenation (n=6, P<0.05), respectively, and the apoptotic rate decreased by 10.92% and 14.34% (n=6, P<0.05) respectively. Hypoxic preconditioning increased the abundance of phospho-ERK1/2 by 3-folds and expression of HIF-1alpha by 1-fold in whole cell extracts from hypoxic preconditioned cardiomyocytes. PD98059, an inhibitor of the upstream kinase of ERKs, abolished the anti-injury effect, ERKs activation, and expression of HIF-1alpha induced by hypoxic preconditioning. Statistical analysis indicated that there was negative correlation between apoptotic rate and activities of ERKs or expression of HIF-1alpha, and positive correlation between activities of ERKs and expression of HIF-1alpha. It is concluded that hypoxic preconditioning protects cardiomyocytes from hypoxia/reoxygenation-induced injury and that upregulation of HIF-1alpha through ERKs pathway mediates the cardioprotection of hypoxic preconditioning.


Applications of Platelet-Rich Plasma in Lymphedema.
Platelet-rich plasma (PRP) is an autologous concentrated preparation of human platelets contained in a small volume of plasma that is characterized by hemostatic and tissue-repairing effects. Being enriched by various kinds of growth factors, and their tissue-repairing effects have made them the focus of attention for use in tissue regeneration. PRP has been safely used and documented in many different fields, including orthopedics, sports injuries, dental and periodontal surgery, and cosmetic, plastic, cardiovascular, general, and maxillofacial surgery. The current evidence obtained from in vitro and animal studies pointed out that PRP may potentially be used to regenerate injured lymphatic vessels to treat or prevent lymphedema. Therefore, we have reviewed existing literature on the clinical uses of PRP in lymphedema and inquired whether there is enough evidence to support the use of PRP in clinical practice as a treatment option. In contrast to in vitro and animal models, there is no clinical trial regarding the use of PRP in lymphedema treatment. Only two animal studies matched to our research yielded positive and promising results in terms of the potential role of PRP in future for lymphedema therapies. In the light of these findings, it is clear that this is an important issue that should be studied in greater depth to clarify the efficacy of PRP in the management of lymphedema.


An extreme-sib-pair genome scan for genes regulating blood pressure.
Hypertension, a risk factor for many cardiovascular, cerebrovascular, and renal diseases, affects one in four Americans, at an annual cost of>$30 billion. Although genetic mutations have been identified in rare forms of hypertension, including Liddle syndrome and glucocorticoid-remediable aldosteronism, the abundance of plausible candidate genes and potential environmental risk factors has complicated the genetic dissection of more prevalent essential hypertension. To search systematically for chromosomal regions containing genes that regulate blood pressure, we scanned the entire autosomal genome by using 367 polymorphic markers. Our study population, selected from a blood-pressure screen of >200,000 Chinese adults, comprises rare but highly efficient extreme sib pairs (207 discordant, 258 high concordant, and 99 low concordant) and all but a single parent of these sibs. By virtue of the sampling design, the number of sib pairs, and the availability of genotyped parents, this study represents one of the most powerful of its kind. Although no regions achieved a 5% genomewide significance level, maximum LOD-score values were >2.0 (unadjusted P<.001) for regions containing five markers (D3S2387, D11S2019, D15S657, D16S3396, and D17S1303), in our primary analysis. Other promising regions identified through secondary analyses include loci near D4S3248, D7S2195, D10S1423, D20S470, D20S482, D21S2052, PAH, and AGT.


Self-assembly of carbon nanotube polyhedrons inside microchannels.
Well-defined carbon polyhedrons with faceted morphologies and hollow internal structures made of self-organized multi-walled carbon nanotubes have been fabricated by gas phase catalytic CVD inside microchannels, of which the confined space is critical for the formation of polyhedral structures with hexagonal, heptagonal and octagonal cross-sections that show superhydrophobic properties, with the contact angle up to 162 degrees .


Potential paths for the introduction of risk analysis to improve the veterinary epidemiology curriculum in Ukraine.
The main purpose of veterinary education institutions is to prepare qualified, well-trained and knowledgeable professionals ready to serve local and global communities. Veterinary programmes vary within and among countries, creating a disparity in competencies. In less-developed economies, adhering to the World Organisation for Animal Health (OIE) 'Day 1 competencies' and following its 'Guidelines for a Model Core Veterinary Curriculum' may decrease this discrepancy. The authors offer a comparison of Ukraine's veterinary epidemiology curriculum with the OIE suggested 'Core Veterinary Curriculum', particularly for infectious disease pathology in which epidemiology is taught, and propose different paths to structure advanced educational programmes in epidemiology. This course is relevant for the development of international animal trade and expansion of markets for animal products in Ukraine.


DNA Biosensor Based on Double-Layer Discharge for the Detection of HPV Type 16.
DNA electrochemical biosensors represent a feasible alternative for the diagnosis of different pathologies. In this work, the development of an electrochemical method for Human Papillomavirus-16 (HPV-16) sensing is reported based on potential relaxation measurements related to the discharge of a complex double layer of a DNA-modified gold electrode. The method used allows us to propose an equivalent circuit (EC) for a DNA/Au electrode, which was corroborated by electrochemical impedance spectroscopy (EIS) measurement. This model differs from the Randles circuit that is commonly used in double-layer simulations. The change in the potential relaxation and associated charge transfer resistance were used for sensing the DNA hybridization by using the redox pair Fe(CN)64-/Fe(CN)63+ as an electrochemical indicator. In order to determinate only the potential relaxation of the composed double layer, the faradic and double-layer current contributions were separated using a rectifier diode arrangement. A detection limit of 0.38 nM was obtained for the target HPV-16 DNA sequences. The biosensor showed a qualitative discrimination between a single-base mismatched sequence and the fully complementary HPV-16 DNA target. The results indicate that the discharge of the double-layer detection method can be used to develop an HPV DNA biosensor.


Ambient glucose and aldose reductase-induced myo-inositol depletion modulate basal and carbachol-stimulated inositol phospholipid metabolism and diacylglycerol accumulation in human retinal pigment epithelial cells in culture.
Physiological hyperglycemia has been speculated to alter phosphoinositide (PPI; inositol phospholipid) signal transduction in cells prone to diabetic complications by two separate mass-action mechanisms with antiparallel putative effects on diacylglycerol (DAG): (i) sorbitol-induced depletion of myo-inositol leads to diminished PPI synthesis and turnover and DAG release, and (ii) elevated glucose-derived DAG precursors enhance de novo DAG synthesis. Because the first mechanism is mediated by aldose reductase (AR2), which converts glucose to sorbitol, the effects of glucose on basal and stimulated PPI signaling were explored in lines of cultured human retinal pigment epithelial cells differing widely in their basal AR2 gene expression and enzymatic activity. The results suggest that the effects of glucose on PPI signaling vary inversely with the level of AR2 activity and parallel the extent of AR2-induced myo-inositol depletion.


Solitary eosinophilic granuloma of the frontal lobe.
Solitary intracranial eosinophilic granulomas are rare and most frequently involve the hypothalamus. We report an unusual case of solitary eosinophilic granuloma of the frontal lobe in a patient without evidence of systemic disease. Previously reported cases of solitary intracranial nonhypothalamic lesions are reviewed, and the clinical, radiographic, and histological features of this case are discussed.


A simple surgical remedy for iatrogenic excessively thick lips.
A technique for the correction of excessively thick lips caused by injections of allogeneic substances is presented in this article. In most cases, surgical removal is the best possible solution to this problem because the materials mentioned above completely blend with the surrounding tissues. Twenty-four patients underwent surgical lip-volume reduction. The results were satisfactory in all of the patients.


Quantification of cellular penetrative forces using lab-on-a-chip technology and finite element modeling.
Tip-growing cells have the unique property of invading living tissues and abiotic growth matrices. To do so, they exert significant penetrative forces. In plant and fungal cells, these forces are generated by the hydrostatic turgor pressure. Using the TipChip, a microfluidic lab-on-a-chip device developed for tip-growing cells, we tested the ability to exert penetrative forces generated in pollen tubes, the fastest-growing plant cells. The tubes were guided to grow through microscopic gaps made of elastic polydimethylsiloxane material. Based on the deformation of the gaps, the force exerted by the elongating tubes to permit passage was determined using finite element methods. The data revealed that increasing mechanical impedance was met by the pollen tubes through modulation of the cell wall compliance and, thus, a change in the force acting on the obstacle. Tubes that successfully passed a narrow gap frequently burst, raising questions about the sperm discharge mechanism in the flowering plants.


Who benefits from fixed-dose combinations? Two-year statin adherence trajectories in initiators of combined amlodipine/atorvastatin therapy.
We compared statin adherence in individuals initiating combined amlodipine/atorvastatin therapy as a fixed-dose (FDC) or free combination and identified subgroups benefiting most from FDCs. We used a 10% sample of Australian Pharmaceutical Benefits Scheme dispensing data (2005-2015) to identify individuals initiating amlodipine and atorvastatin as an FDC (n = 3996) or free combination (n = 5434), with or without prior statin dispensing. We measured the proportion of days covered in each 30-day period over 24 months and classified patterns of statin adherence using group-based trajectory models. We identified predictors of adherence trajectories using logistic regression. The median age was 71 years, and 53% were female. We identified 4 patterns of statin adherence: near-perfect adherence (n = 5383), good adherence (n = 1893), declining adherence (n = 1247), and early nonadherence (n = 907). Compared with the free combination, FDC initiators were more likely to have near-perfect adherence if they were previously statin adherent irrespective of amlodipine dose (amlodipine 5 mg: OR = 1.61, 95% CI 1.38-1.87; amlodipine 10 mg: OR = 2.39, 95% CI 1.63-3.51) or they were previously statin nonadherent and initiated on the 5 mg amlodipine dose (OR = 1.87, 95% CI 1.50-2.32). Statin-naïve individuals initiating on the FDC with 10 mg amlodipine were less likely to have near-perfect adherence (OR = 0.60, 95% CI 0.41-0.88) and more likely to have early nonadherence (OR = 1.73, 95% CI 1.17-2.55). The amlodipine/atorvastatin FDC was associated with greater statin adherence among prevalent statin users, and individuals who initiated on lower amlodipine doses. The FDCs did not improve adherence in statin-naïve individuals and in some cases resulted in poorer adherence.


Oral paricalcitol versus oral calcitriol in continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism.
Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease. Our primary objective was to evaluate the efficacy of oral paricalcitol versus oral calcitriol on serum intact parathyroid hormone (iPTH) and mineral bone parameters in continuous ambulatory peritoneal dialysis (CAPD) patients with SHPT. The secondary objective was to analyze highly sensitive C-reactive protein (hsCRP) and peritoneal membrane function in both groups. This was a prospective randomized control trial. CAPD patients with SHPT were randomized to paricalcitol or calcitriol for 15 weeks. Serum intact iPTH, calcium, phosphate and alkaline phosphatase (ALP) were measured at baseline and every 3 weeks. Serum hsCRP and peritoneal membrane functions were measured at baseline and at week 15. A total of 26 patients were enrolled and randomized-12 to paricalcitol and 14 to calcitriol. Serum iPTH reduced significantly in both groups and there was no difference in the incidence of ≥50 % reduction of iPTH between both groups. There was a significant increase in serum calcium in both groups but there were no differences in serum phosphorus across the visits. The incidence of hypercalcemia was the same in both groups. Serum calcium-phosphorus (Ca × P) product increased in the paricalcitol group but decreased in the calcitriol group. Serum ALP decreased significantly in both groups. There were also no differences in pre- and post-treatment serum hsCRP and peritoneal function test (PFT) in both groups. Both oral paricalcitol and calcitriol were equally efficacious in reducing serum iPTH but were associated with significantly higher serum calcium. Serum Ca × P product increased in the paricalcitol group and decreased in the calcitriol group. Serum hsCRP level and PFT were not affected by either treatment. A larger randomized controlled trial is indicated to confirm these initial findings.