Potassium efflux induced by a new lactoferrin-derived peptide mimicking the effect of native human lactoferrin on the bacterial cytoplasmic membrane.
A 31-amino acid synthetic peptide (NH(2)-FFSASCVPGADKGQFPNLCRLCAGTGENKCA-COOH) was chemically synthesized based on the amino acid sequence of a region of human lactoferrin homologous to other sequences present in the N- and C-lobes of all members of the transferrin family proteins. The peptide, termed kaliocin-1, and lactoferrin showed a bactericidal effect in assays performed in low-ionic-strength conditions. This is the first time that it is shown that the antimicrobial effect of lactoferrin depends on the extracellular cation concentration. The antimicrobial effect of kaliocin-1 was lower than that of human lactoferrin, but their activities were inhibited by Na(+) or K(+) in a cation concentration-dependent manner. In addition, the peptide was able to mimic native lactoferrin, inducing K(+)-efflux and a selective dissipation of the transmembrane electrical potential of Escherichia coli cells without causing extensive damage to the outer and inner bacterial membranes. In contrast, the peptide, but not lactoferrin, was able to permeabilize different ions through liposomal membranes. The hypothetical interaction of kaliocin-1 with a bacterial membrane compound is discussed based in the different ion flux induced on cellular and artificial membranes as well as data from circular dichroism assays. Kaliocin-1 was not cytotoxic and could be a suitable model for the design of analogs able to mimic the antibacterial effect of human lactoferrin.


[Tobacco consumption and nicotine dependence. A study of adolescents].
A look at the prevalence of tobacco use and the degree of nicotine dependency in a group of 14 to 18 year olds. The authors emphasize that this age group needs to be presented with preventative smoking activities in order to forestall tobacco addiction; it has been clearly demonstrated that it is much easier to prevent tobacco dependency than to eliminate it.


Hepatitis B vaccine usage among dental practitioners in the United States: an epidemiological survey.
A telephone survey of 283 nonfederally affiliated dental practitioners in the United States was completed in April 1986. The study's objectives were to determine hepatitis B vaccine usage among dentists nationwide, and to examine the epidemiologic characteristics of vaccinated and unvaccinated subjects. Forty-four percent of the participants had received at least the first of the three doses of HB vaccine. Acceptance of the vaccine was associated with the use of gloves during dental procedures and the subject's perception of high-risk patients in his or her dental practice. The most common reasons for not being vaccinated were concerns about vaccine safety and a lack of perceived need for the vaccine. The vaccination rate in this survey is higher than in earlier studies, indicating that acceptance of the vaccine by dental practitioners is increasing.


Rheological properties of concentrated solutions of galactomannans in an ionic liquid.
The rheological behavior of galactomannans in concentrated solutions was examined by using dynamic viscoelasticity measurements. Concentrated solutions of three galactomannans, guar gum, tara gum, and locust bean gum were prepared with an ionic liquid 1-butyl-3-methylimidazolium chloride as the solvent. Each galactomannan solution showed angular frequency dependence curves of the storage modulus and the loss modulus which were characteristic of a solution of entangled polymer chains. The molecular weight between entanglements (Me) was obtained from the plateau modulus and the concentration dependence of Me showed Me in the molten state (Me,melt) to be 4.6×10(3), 3.2×10(3), and 2.7×10(3) for guar gum, tara gum, and locust bean gum, respectively. It was found that the material constant Me,melt depends on the mannose/galactose ratio of the galactomannans. The number of monosaccharide units between entanglements in the molten state for the galactomannans varied within the range found for other polysaccharides such as cellulose and agarose in ionic liquids, suggesting that all the galactomannans take a random-coil conformation in ionic liquid solutions.


PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease.
Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive (AR) disorder characterized by motor symptoms as such as dystonia or parkinsonism, mental retardation, retinitis pigmentosa and iron accumulation in the brain. As many neurodegenerative conditions have similar clinical features we screened a number of adult and childhood onset movement disorders for PANK2 mutation. This included cases with neurodegeneration and brain iron accumulation, corticobasal degeneartion, progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atropy, giant axonal neuropathy (GAN), neuroaxonal dystrophy (NAD), Guam dementia and HARP syndrome (pallido-pyramidal syndrome and hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration). From our series of patients one patient with PKAN and a progressive severe dystonic syndrome, cerebellar ataxia, retinitis pigmentosa and eventual anarthria had a novel combination of two compound heterozygote mutations identified in the PANK2 gene, G-->A transition at base 1238 (G411R) and a C-->A transition at base 1184 (A395E). In the patient with HARP syndrome two compound heterozygote mutations (Met327Thr and IVS5-1 G to T) in the PANK2 gene were found. No other mutations were found in any of the other patient groups, suggesting that PANK2 mutations are not associated with the aetiology of these adult degenerative conditions and confirms the genetic heterogeneity in neurodegeneration with brain iron accumulation.


Intrathecal Administration of Losartan Reduces Directly Recorded Cardiac Sympathetic Nerve Activity in Ovine Heart Failure.
Early and preferential activation of cardiac sympathetic nerve activity (CSNA) is one of the strongest prognostic markers of heart failure (HF) in patients. Our previous studies have implicated central angiotensin mechanisms as playing a critical role in generating this increase in cardiac sympathetic drive. However, it is unclear if inhibition of AT1R (angiotensin type-1 receptors) in different neural groups in the sympathetic pathway to the heart, such as the sympathetic preganglionic neurons in the intermediolateral column of the spinal cord, can reduce cardiac sympathetic drive. We hypothesized that in HF, localized intrathecal administration of the AT1R antagonist losartan, specifically into the T1-2 subarachnoid space, would decrease CSNA. In normal conscious sheep, intrathecal infusion of Ang II (angiotensin II; 3.0 nmol/mL per hour), significantly increased mean arterial pressure and CSNA; this effect was abolished by prior administration of losartan (1 mg/h). In an ovine rapid ventricular pacing model of HF, the resting levels of heart rate and CSNA were significantly elevated compared with normals. Intrathecal infusion of losartan (1 mg/h) in HF significantly reduced CSNA and heart rate but did not change arterial pressure. The AT1R binding density in the spinal cord was also elevated in the HF group. Our data suggest that AT1Rs within the spinal cord are responsible, in part, for the increased CSNA in HF and may represent a target for the selective reduction of CSNA in HF.


Oncogenic microRNAs as biomarkers of oral tumorigenesis and minimal residual disease.
Classical diagnostic methods are not sensitive enough in detecting oral lesions that may progress to cancer and in assessing minimal residual disease (MRD) in oral surgical margins. Altered expression of microRNAs (miRNAs) contributes to human cancer, including oral cancer. Although there are many studies on microRNAs in oral cancer, there is no reported study comparing the expression of microRNAs during oral tumor progression and in oral surgical margins. This study analyzed the expression of 72 miRNAs that were reported (till June 2011) to be differentially expressed in oral cancer, during phases of oral cancer progression and in oral surgical margins. Of the 72 miRNAs analyzed, four (hsa-miR-125a, hsa-miR-184, hsa-miR16 and hsa-miR-96) showed a common pattern of expression in both sets of tissues. We further analyzed the downstream target genes of hsa-miR-16 BCL2 and CCND1. The in silico network analysis of these four microRNAs and their target genes revealed presence of genes involved in tumor progression and transcription factors. The findings suggest that the combinatorial regulation by these miRNAs and their target transcription factors might play a substantial role in oral tumorigenesis. Here we report for the first time that a decreased expression of hsa-miR-125a, hsa-miR-184 and hsa-miR-16 and an increased expression of hsa-miR-96 could be useful in predicting oral tumorigenesis and importantly in the detection of MRD and decision-making process for postoperative treatment modalities.


Drosophila immunity research on the move.
Drosophila has been established as useful model for infectious diseases because it allows large numbers of whole animals to be studied and provides powerful genetic tools and conservation with signaling and pathogenesis mechanisms in vertebrates. During the past twenty years, significant progress has been made on the characterization of innate immune responses against various pathogenic organisms in flies (Fig. 1). In this year's Drosophila Research Conference, which was held in San Diego (March 30-April 3) and sponsored by the Genetics Society of America, the immunity and pathogenesis session comprised seven platform presentations and 34 posters that highlighted the latest advances in Drosophila infection and immunity field. The presented work covered a wide range of studies from immune signaling pathways and the molecular basis of humoral and cellular immune mechanisms to the role of endosymbionts in fly immune function and effects of immune priming. Here, we give an overview of the presented work and we explain how these findings will open new avenues in Drosophila immunity research.


Etiology, treatment, and outcome of esophageal ulcers: a 10-year experience in an urban emergency hospital.
Esophageal ulcers are a rare cause of upper gastrointestinal bleeding. This report describes the etiology, treatment, complications, and outcome of esophageal ulcers. An esophageal ulcer is defined as a discrete break in the esophageal mucosa with a clearly circumscribed margin; esophageal ulcers were seen in 88 patients from a total of 7,564 esophagogastroduodenoscopies done by one surgeon at an urban hospital from 1991 to 2001. All hospital reports were reviewed. The etiology of esophageal ulcers included the following: gastrointestinal reflux disease (GERD) (n=58, 65.9%), drug induced (n=20, 22.7%), candidal (n=3, 3.4%), caustic injury (n=2, 2.3%), and herpes simplex virus (HSV), human immunodeficiency virus (HIV), marginal ulcer, foreign body, and unknown etiology (n=1 of each, 1.1%). The mean size of GERD-induced esophageal ulcers and drug-induced esophageal ulcers was 2.78 and 2.92 cm, respectively; 80.3% of GERD-induced esophageal ulcers and 13.8% of drug-induced esophageal ulcers were located in the lower thoracic esophagus. Morbidity (n=44, 50%) included hemorrhage (n=30, 34%), esophageal stricture (n=11, 12.5%), and esophageal perforation (n=3, 3.4%). Nonoperative therapy sufficed in 81 patients (92%). Three patients (3.4%) had a recurrence of esophageal ulcers. Fifteen patients (17.0%) required endoscopic intervention including esophageal dilatation for stricture in 11 patients and endoscopic hemostasis for esophageal bleeding in four patients. Surgery (n=7, 8.0%) was reserved for esophageal stricture and perforation. Two patients (2.3%) died from complications of esophageal ulcers: hemorrhage in one and perforation in one. Three patients died of their primary disease. GERD and drug ingestion are common causes of esophageal ulcers. Midesophageal ulcers have a greater tendency to hemorrhage compared with ulcers at the gastroesophageal junction; this may reflect the etiology. Strictures complicate GERD-induced esophageal ulcers but not drug-induced esophageal ulcers. Esophageal dilatation is an effective treatment for most strictures associated with esophageal ulcers. Esophageal ulcers rarely cause death.


[The effect of the actoprotector preparation bromantane on the postnatal development of rat pups].
The purpose of this work was study of the late-term results of a course of the actoprotector bromantan on the formation and development of the rat progeny. Bromantan was given per os daily in doses of 30, 150, and 600 mg/kg once a day: females received the drug for 15 days (2.5 estrous cycles), males for 60 days (whole cycle of spermatogenesis). When the course of treatment with the drug ended, the females were put together with the males for two weeks. The experiments were subdivided into two series: in series I the progeny obtained from coupling of experimental males with intact females was studied, in series II the progeny of intact males and experimental females. According to the results of the investigation, bromantan produced a late-term effect on the formation and development of the offsprings. The number of females who gave birth in series I and II of the experiment, despite a low dose-dependent increase, did not differ significantly from the controls. In series I of the experiment the litter increased insignificantly depending on the dose (by 0.3, 14.9, and 23.4%, respectively). In distinction, in the case of experimental females given 30 and 600 mg/kg bromantan before copulation (series II) the number of young rats in the litter insignificantly reduced (by 34.9 and 44.2%), in the case of rats given 150 mg/kg bromantan the litter increased (by 45%, p < 0.05). Both in series I and series II the mean weight of the newborns in the first week was significantly higher than the weight of the controls. After that the growth in body weight was insignificantly slower. Evaluation of the functional condition of the nervous system and terms of physical development of the progeny in series I and II of copulation showed an insignificant increase in the rate of maturation of the sensorimotor reflexes and physical parameters of the young experimental rats. The "open-field" test conducted on the 40th day of life showed increase of motor (by 8.0-21.6%) and exploration activity (by 94.5-109.9%, p < 0.05) in the young experimental rats of series I and, at the same time, decrease of the grooming parameters (by 26.9-63.5%, p < 0.05) and emotionality. In all experimental groups of series II horizontal and vertical motor and searching activity was reduced. The authors believe that the actoprotector bromantan, possessing a dopaminergic effect in the mechanism of its action, may cause a late-term influence on prolactin secretion in lactating rats. The deficiency in this hormone in the early period of postnatal development affects the neurochemical organization of the hypothalamo-hypophyseal region and the brain areas connected with it, involving in this case also the mechanisms of sexual differentiation of the brain and, as a consequence, the somatic and sexual development of the progeny.


Subspecialty impact factors: the contribution of pediatric anesthesia and pain articles.
The Science Citation Index "Journal Impact Factor" (JIF) is widely used to assess journal quality and prestige. The JIFs for the specialty anesthesia are reported annually, however, the impact factors (IFs) for subspecialties in those journals have not been reported. Therefore, we compared the IFs of pediatric anesthesia (Ped IFs) and pain (Pain IFs) articles from four anesthesia journals for two epochs. An article-by-article manual search for "source" pediatric anesthesia and pain articles published in 1998, 1999, 2003, and 2004 in Anesthesiology, Anesthesia & Analgesia, British Journal of Anaesthesia, and Canadian Journal of Anesthesia was performed. The citations for each of these articles in each of the years were surveyed in the ISI Web of Science database. Ped IFs and Pain IFs for the 2000 and 2005 epochs were calculated and compared with the JIF from which they were derived and to those of the journal, Pediatric Anesthesia. Ped IFs for the four journals in 2005 exceeded those in 2000, whereas the Pain IFs were unchanged. For both the Ped IFs and the Pain IFs, there was a significant effect of the journal. The Pain IFs were 70% greater than the Ped IFs. Ped IFs were consistently less than the JIFs in which they were published and the Pain IFs, except for the British Journal of Anaesthesia 2005 in the latter case. The numbers of citations of pediatric anesthesia articles were greater in journals with greater IFs. The implications of subspecialty IFs warrant further consideration.


A Pid3 allele from rice cultivar Gumei2 confers resistance to Magnaporthe oryzae.
Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases. Using map-based strategy and in silico approach we isolated a new rice (Oryza sativa L.) blast resistance allele of Pid3, designated Pi25, from a stable blast resistance cultivar Gumei2. Over-expression analysis and complementation test showed that Pi25 conferred blast resistance to M. oryzae isolate js001-20. Sequence analysis showed that Pi25 was an intronless gene of 2,772 nucleotides with single nucleotide substitution in comparison to Pid3 at the nucleotide position 459 and predicatively encoded a typical coiled coil--nucleotide binding site--leucine rich repeat (CC--NBS--LRR) protein of 924 amino acid residuals with 100% identity to Pid3 putative protein. The susceptible allele pi25 in Nipponbare contained a nonsense mutation at the nucleotide position 2,209 resulting in a truncated protein with 736 amino acid residuals. In addition, 14 nucleotide substitutions resulting in 10 amino acid substitutions were identified between Pi25 and pi25 upstream the premature stop codon in the susceptible allele. Although the mechanism of Pi25/Pid3-mediated resistance needs to be further investigated, the isolation of the allele would facilitate the utilization of Pi25/Pid3 in rice blast resistance breeding program via transgenic approach and marker assisted selection.


Influence of moderate energy restriction and seafood consumption on bone turnover in overweight young adults.
Overweight and obesity are increasing in young adults. However, moderate energy restriction aimed at lowering body weight may promote bone turnover and bone loss. Inclusion of fish or fish oils in a weight-loss diet may attenuate these adverse skeletal effects. We examined the effects of incorporating fish or fish oil into an energy-restricted diet on bone turnover markers in young overweight adults. While following a strict hypoenergetic (-30% relative to estimated requirements) diet for 8 wk, 276 overweight men and women [body mass index (in kg/m(2)): 27.5-32.5; age: 20-40 y) were randomly assigned to 1 of 4 dietary groups: sunflower-oil capsules (3 g/d; control), cod (3 x 150 g/wk), salmon (3 x 150 g/wk), and fish-oil capsules (3 g/d). Body weight, bone biomarkers, and 25-hydroxyvitamin D were measured at baseline and endpoint. Data were analyzed with repeated-measures analysis of variance and general linear models. The mean (+/-SD) weight loss was 5.14 +/- 3.0 kg (5.8% +/- 3.2% body weight) during the 8 wk in the 4 dietary groups combined. Urinary N-telopeptides of type I collagen and serum C-terminal telopeptide of type I collagen increased (P < 0.05), whereas serum osteocalcin (but not bone-specific alkaline phosphatase) decreased (P < 0.05) from baseline to endpoint. Increased fish or fish-oil consumption had no effect (P > 0.1) on the changes in bone markers induced by weight loss. In contrast, increased salmon consumption increased serum 25-hydroxyvitamin D (P < 0.01). A nutritionally adequate but energy-restricted diet, with different contents of n-3 fatty acids, which resulted in modest weight loss, unfavorably altered bone turnover markers in young overweight adults. Such changes were not prevented by increased fish or fish-oil consumption.


Electronically Stabilized Nonplanar Phenalenyl Radical and Its Planar Isomer.
Stable phenalenyl radicals have great potential as the basis for new materials for applications in the field of molecular electronics. In particular, electronically stabilized phenalenyl species that do not require steric shielding are molecules of fundamental interest, but are notoriously difficult to synthesize. Herein, the synthesis and characterization of two phenalenyl-type cations is reported: planar benzo[i]naphtho[2,1,8-mna]xanthenium (8(+)) and helical benzo[a]naphtho[8,1,2-jkl]xanthenium (9(+)), which can be reduced to the corresponding radicals. Radical 9 represents the first stable, helical phenalenyl radical which does not rely on bulky substituents to ensure its stability. Both cations are water-soluble, and the radicals are stable for weeks at room temperature under air. These compounds were characterized crystallographically, and also by NMR, EPR, electrochemistry, and electronic spectra. The synthesis of the previously reported compound benzo[5,6]naphthaceno[1,12,11,10-jklmna]xanthylium (5(+)), the largest oxygen-containing polycyclic hydrocarbon, was undertaken for comparison with 8(+) and 9(+), allowing us to report its crystal structure here for the first time. The different properties of these compounds and their radicals are explained by considering their differing aromaticities using in-depth computational methods.


Toward Neuroproteomics in Biological Psychiatry: A Systems Approach Unravels Okadaic Acid-Induced Alterations in the Neuronal Phosphoproteome.
Neuroproteomics is an evolving field of postgenomic medicine, highlighting the convergence of psychiatry/neurology and proteomics, yet compared with neurogenetics, it has received little attention. This study in rat primary neuronal cultures provides an example of a neuroproteomic approach relevant to the study of psychiatric disease pathophysiology, focusing on Alzheimer's disease. In this context, okadaic acid (OA) is routinely used in experimental designs to investigate phosphorylation-mediated events. It is a potent protein phosphatase (PP) inhibitor, particularly of PP1 and PP2A. Typically, a single protein and its phosphorylation level are monitored upon OA exposure. Although useful, this can be misleading as protein phosphorylation-mediated events involve complex signaling cascades and an array of kinases, phosphatases, and substrates. Bearing in mind the involvement of multiple pathways and cascade cross talk, this study employed a systems approach to analyze OA-induced molecular responses through PP inhibition. We showed that upon OA exposure, the recovery rate of 245 phosphoproteins significantly increased, while that of 75 significantly decreased. The prominent biological processes affected included anatomical structural development, transport, cell differentiation, and signal transduction. The associated phosphointeraction networks identified nodes representing OA-responsive phosphoproteins. Many of these are key players of signaling cascades relevant to a range of pathologies. In summary, the data presented results from a neuroproteomic preclinical study offering an array of phosphoproteins as potential targets for future diagnostic and therapeutic strategies in biological psychiatry. We note, however, the nonspecificity of targeting PPs themselves and emphasize the need for future neuroproteomic approaches toward systems psychiatry.


Hyperthyroidism as a cause of persistent choreic movements.
A patient is described who had thyrotoxicosis more than 30 years ago and suffers since that time from presistent choreic movements. This case suggests for the first time that chorea induced by hyperthyroidism may outlast the endocrine disorder and become irreversible.


Network analysis and percolation transition in hydrogen bonded clusters: nitric acid and water extracted by tributyl phosphate.
Extraction of polar molecules by amphiphilic species results in a complex variety of clusters whose topologies and energetics control phase behavior and efficiency of liquid-liquid separations. A computational approach including quantum mechanical vibrational frequency calculations and molecular dynamics simulation with intermolecular network theory is used to provide a robust assessment of extractant and polar solute association through hydrogen bonding in the tributyl phosphate (TBP)/HNO3/H2O/dodecane system for the first time. The distribution of local topologies of the TBP/HNO3/H2O hydrogen bonded clusters is shown to be consistent with an equilibrium binding model. Mixed TBP/HNO3/H2O clusters are predicted that have not been previously observable in experiment due to limitations in scattering and spectroscopic resolution. Vibrational frequency calculations are compared with experimental data to validate the experimentally observed TBP-HNO3-HNO3 Chain structure. At high nitric acid and water loading, large hydrogen-bonded clusters of 20 to 80 polar solutes formed. The cluster sizes were found to be exponentially distributed, consistent with a constant average solute association free energy in that size range. Due to the deficit of hydrogen bond donors in the predominantly TBP/HNO3 organic phase, increased water concentrations lower the association free energy and enable growth of larger cluster sizes. For sufficiently high water concentrations, changes in the cluster size distribution are found to be consistent with the formation of a percolating cluster rather than reverse micelles, as has been commonly assumed for the occurrence of an extractant-rich third phase in metal-free solvent extraction systems. Moreover, the compositions of the large clusters leading to percolation agrees with the 1 : 3 TBP : HNO3 ratio reported in the experimental literature for TBP/HNO3/H2O third phases. More generally, the network analysis of cluster formation from atomic level interactions could allow for control of phase behavior in multi-component solutions of species with a variety of hydrogen bond types.


Beta-adrenoceptor activity and resting energy metabolism in weight losing cancer patients.
This study was aimed at comparing the blocking of beta-adrenoceptor activity to changes in the resting energy metabolism of 10 cancer patients with progressive weight loss due to solid malignant tumours. Resting energy expenditure (REE) as well as whole body carbohydrate and fat oxidation were investigated and related to plasma substrate levels (glucose, glycerol, free fatty acids (FFA)) before and after 5 days of oral administration of specific beta1 receptor blocker (atenolol, 50 mg/day) and non-specific beta1,beta2-adrenoceptor (propranolol, 80 mg/day) blockade. The administration order of the drugs was random, and a 3-day washout period was used in all individuals between the provision of the first and the second drug in order to minimise the risk of carry-over effects. Resting measurements in the morning after an overnight fast were performed by indirect calorimetry. Atenolol treatment reduced REE by 77+/-14 kcal/day and propranolol by 48+/-13 kcal/day, respectively (P<0.05 versus pretreatment values). Whole body oxygen uptake and carbon dioxide production were decreased similarly by both atenolol and propranolol treatment (P<0.05). Carbohydrate oxidation was increased by atenolol and decreased by propranolol, whilst fat oxidation was decreased by atenolol and unchanged by propranolol. The decrease in REE, accounting for the decline in heart rate, was significantly more pronounced following treatment with propranolol compared with atenolol (P<0.05). Atenolol and propranolol had no effect on blood glucose, plasma glycerol and FFA. We conclude that wastage in cancer patients is in part explained by increased beta(1) and beta(2)-adrenoceptor activity, in part secondary to elevated cardiovascular activity as a result of anaemia, loss of cardiac contractile capacity and altered host metabolism.


Life-threatening ventricular tachycardia as the presenting symptom of metastatic cardiac disease.
We present 2 cases in whom repetitive rapid ventricular tachycardia (VT) was the initial manifestation of metastatic cardiac disease. In one patient, repetitive VT appeared during chemotherapy for stage IV paratesticular rhabdomyosarcoma which led to the diagnosis of cardiac metastases. In the other, it led to the diagnosis of malignant pericardial effusion 17 years after successful therapy for a breast carcinoma. In conclusion, in patients with present or past history of malignancy, the appearance of life-threatening VT should raise the suspicion of cardiac metastases.


Degenerate recognition and response of human CD4+ Th cell clones: implications for basic and applied immunology.
It was once considered that the T cell response is an all or nothing type event, but recent studies have clearly indicated that T cells show many different types of activation in recognition of altered ligands for T cell receptors (TCR). In this review, we summarize our recent findings on the response of human CD4+ helper T (Th) cell clones to altered peptide ligands (APL); peptides carrying single or multiple residue substitutions in antigenic peptides. The extensive analyses revealed that TCR-antagonism and partial agonism are frequently observed by the stimulation with APLs substituted at particular amino acid residues of antigenic peptides. We observed unique partially agonistic APLs inducing prolongation of T cell survival without cell proliferation. Superagonistic APLs stimulated enhanced proliferation and production of cytokines in Th cell clones reactive to tumor-associated antigens. The other APL induced enhanced production of interleukin-12 by antigen presenting cells and subsequent enhancement of IFN-gamma production by T cells reactive to allergens. By utilizing an HLA-DR-restricted T cell epitope library generated by mutated invariant chain genes, it was revealed that human Th cell clones recognize a more diverse array of peptides with multiple and simultaneous amino acid substitutions in an antigenic peptide. APLs also induced altered intracellular signaling events including intracellular calcium increase and phosphorylation of signaling molecules. This information provides basic knowledge regarding the characteristics of antigen recognition by human Th cells and the subsequent activation, and a novel method for manipulation of human Th cell responses by APLs, as a possible candidate for antigen-specific immuno-potentiating or immunosuppressive therapy.


Biofilm dynamics and EPS production of a thermoacidophilic bioleaching archaeon.
Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process. In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice. Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite. Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited. The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp. DSM 29099 under bioleaching conditions. The results show that biofilms are dispersed non-homogeneously on pyrite. Large parts of the pyrite surfaces remain free of cells. Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds. A monolayer biofilm develops on pyrite after 2-4 days of incubation. In addition, the pyrite surface is covered with a layer of organic compounds. EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells). This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments. Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.


Torture by Cieng: ethical theory meets social practice among the Dinka Agaar of south Sudan.
Here I detail violence in South Sudan by first discussing a specific Dinka Agaar practice alongside existing discourses on the social aspects of violence and universal human rights, then I show how these acts had meaning and purpose using data from personal accounts of violence. I posit that the violence described was consistent with Dinka Agaar concepts of justice and basic human rights and that it cannot be judged against any universal human rights standard, devoid of local context or of an overarching metanarrative. These events highlight conflicting subjectivities, ethical norms, and the painful difficulties inherent to advocacy in areas of conflict. Viewed from the perspective of the larger social unit, it is easy to see how violence was required to end violence. However, witnessing punitive violence purposefully enacted on innocent individuals to achieve peace has the potential to create conflicting positions that modern anthropological discourse cannot reconcile.


Perceptual grouping impairs temporal resolution.
Performance on multisensory temporal order judgment (TOJ) tasks is enhanced when the sensory stimuli are presented at different locations rather than the same location. In our first experiment, we replicated this result for spatially separated stimuli within the visual modality. In Experiment 2, we investigated the effect of perceptual grouping on this spatial effect. Observers performed a visual TOJ task in which two stimuli were presented in a configuration that encouraged perceptual grouping or not (i.e., one- and two-object conditions respectively). Despite a constant spatial disparity between targets across the two conditions, a smaller just noticeable difference (i.e., better temporal resolution) was found when the two targets formed two objects than when they formed one. This effect of perceptual grouping persisted in Experiment 3 when we controlled for apparent motion by systematically varying the spatial distance between the targets. Thus, in contrast to the putative same-object advantage observed in spatial discrimination tasks, these findings indicate that perceptual grouping impairs visual temporal resolution.


A technique to reposition sinotubular junction in aortic valve reimplantation procedures with the De Paulis Valsalva graft.
Sinotubular junction reconstruction in reimplantation type of valve-sparing aortic procedure can present some problem when a Valsalva graft is used. Since in the Valsalva graft the sinotubular junction height is predetermined, correct matching with native commissures height can be difficult. We propose a method by which it is possible to create a new sinotubular junction in Valsalva graft without altering its original configuration.


Ultrasensitive flow injection chemiluminescence detection of DNA hybridization using signal DNA probe modified with Au and CuS nanoparticles.
A novel and sensitive flow injection chemiluminescence assay for sequence-specific DNA detection based on signal amplification with nanoparticles (NPs) is reported in the present work. The "sandwich-type" DNA biosensor was fabricated with the thiol-functionalized capture DNA first immobilized on an Au electrode and hybridized with one end of target DNA, the other end of which was recognized with a signal DNA probe labeled with CuS NPs and Au NPs on the 3'- and 5'-terminus, respectively. The hybridization events were monitored by the CL intensity of luminol-H2O2-Cu(2+) after the cupric ions were dissolved from the hybrids. We demonstrated that the incorporation of Au NPs in this sensor design significantly enhanced the sensitivity and the selectivity because a single Au NP can be loaded with hundreds of signal DNA probe strands, which were modified with CuS NPs. The ratios of Au NPs, signal DNA probes, and CuS NPs modified on the gold electrode were approximately 1/101/103. A preconcentration process of cupric ions performed by anodic stripping voltammetry technology further increased the sensor performance. As a result of these two combined effects, this DNA sensor could detect as low as femtomolar target DNA and exhibited excellent selectivity against two-base mismatched DNA. Under the optimum conditions, the CL intensity was increased with the increase of the concentration of target DNA in the range of 2.0 x 10(-14)-2.0 x 10(-12) M. A detection limit of 4.8 x 10(-15) M target DNA was achieved.


Modulation of involuntary attention by the duration of novel and pitch deviant sounds in children and adolescents.
In a passive auditory oddball event-related potential study, the processing of short (100 ms) and long (500 ms) novels and pitch deviant tones was investigated in three age groups (6-8, 10-12, and 17-18 years). Age specific distributions of P3a demonstrate developmental differences in the processing of unexpected sounds. Moreover, long compared with short novel sounds (but not long compared with short pitch deviant tones) elicited enhanced positive brain waves in early (200-300 ms) and late (300-400 ms) P3a as well as in post-P3a (400-600 ms) windows. This finding suggests stronger attentional capture for unexpected sounds with higher information content. The fact that in the post-P3a window this duration effect was largest for the 6-8 years old indicates that young children are especially prone for distraction.


Is fourth-line chemotherapy routine practice in advanced non-small cell lung cancer?
Despite advances in palliative chemotherapy, patients with advanced non-small cell lung cancer (NSCLC) eventually experience disease progression during or after completion of first-line chemotherapy, which requires salvage therapy. Second- or third-line therapy in selected patients is recommended in the current guidelines. Although fourth-line therapy is often performed in daily practice in some countries, there are few reports about the clinical benefits of fourth-line therapy. A retrospective review was conducted on 383 patients who underwent at least first-line palliative chemotherapy for advanced NSCLC (stage IV or stage IIIB/recurrent disease unsuitable for definitive local therapy). Overall survival (OS) and clinicopathological characteristics were analyzed according to the lines of chemotherapy as well as for all study patients. The median OS for all patients after the initiation of first-line therapy was 11 months. The median OS for patients who received fourth- or further-line therapy (77 patients) was longer than that of patients who received third- or lesser-line therapy (27 versus 9 months, p<0.0001). In multivariate analysis, fourth- or further-line therapy was independently associated with favorable OS (hazard ratio: 0.44, 95% confidence interval: 0.34-0.57, p<0.0001) along with recurrent disease, female, age <70 years, and ECOG performance status (PS) 0 or 1. Median OS after the start of fourth-line therapy was 9 months. Good PS (ECOG PS 0, 1) at the initiation of fourth-line therapy (10 versus 2 months, p<0.0001) and disease control (10 versus 7 months, p=0.011) after first-line therapy were associated with favorable OS in univariate analysis, while poor PS (ECOG PS ≥2) was an independent prognostic factor for poor outcome (p<0.0001). The present study suggests that advanced NSCLC patients with good PS after progression from third-line therapy could be considered as reasonable candidates for fourth-line therapy in clinical practice.


Dopaminergic deficit and mood disorders.
The roles of serotonin and noradrenaline in the pathogenesis of mood disorders have been elucidated by numerous studies, which support the therapeutic use of tricyclic antidepressants and selective serotonin re-uptake inhibitors. The same has not occurred for dopamine, notwithstanding the fact that the crucial role of the mesolimbic dopaminergic system in behaviour has been known to researchers for many years. The objective of this article is to provide an overview of the animal data that demonstrate the importance of dopamine in animal behaviour and suggest that dopaminergic deficiency may cause a number of psychiatric symptoms in man.


Conduit options in coronary artery bypass surgery.
The choice of graft conduit is crucial to the success of coronary artery bypass grafting (CABG) because the patency of a coronary conduit is closely associated with an uneventful postoperative course and a better long-term patient survival. The standard conduits used for CABG are the greater saphenous vein (GSV) and the internal thoracic artery (ITA). An excellent substitute conduit for coronary bypass operations that can be taken "off the shelf" is certainly the dream of every practicing cardiac surgeon. However, virtually every synthetic and biologic alternative to arterial conduits or autologous fresh saphenous vein has proved disappointing. Fortunately, patients with absolutely no autologous conduit alternatives are uncommon. Circumstances exist, however, that often necessitate the use of alternative conduits such as young hyperlipemic patients, absent or unsuitable autologous ITAs and GSV as a result of previous myocardial revascularization, peripheral arterial reconstruction, and varicose vein ligation procedures. This review provides an update on the clinical work done with all coronary conduits available for myocardial surgical revascularization.


Effect of estradiol on plasma melatonin levels.
Melatonin levels were determined in plasma samples obtained at 15 minute intervals during a 4-hour period (08:00 - 12:00 hours) from a normal adult male on 5 consecutive days. On days 1, 2, and 3, the subject was given estradiol valerate (E2) 10 micrograms/kg at the end of each sampling period. An episodic pattern of melatonin secretion was found. Post E2 mean estradiol levels per 4 hours increased and mean melatonin and testosterone levels per 4 hours decreased significantly. A decrease in melatonin levels post E2 is the reverse of the response expected based on nonhuman animal experimental data.


Treatment of alcoholic polyneuropathy with vitamin B complex: a randomised controlled trial.
To evaluate the therapeutic efficacy and safety of BEFACT Forte 'new formulation' and BEFACT Forte 'old formulation' in the treatment of sensory symptoms of alcoholic polyneuropathy. A multi-centre, randomised, double-blind, placebo-controlled study was conducted on 325 patients with sensory symptoms and signs of alcoholic polyneuropathy. Patients were randomised to the 'old formulation' (i.e. vitamins B1, B2, B6, and B12), 'new formulation' [i.e. identical to the 'old formulation' with additional folic acid (vitamin B9)], or placebo in a 1:1:1 ratio. One tablet of the study medication ('new formulation' or 'old formulation') or placebo was taken orally, three times a day, over a 12-week treatment period. Therapeutic efficacy was assessed in 253 patients by measuring vibration perception threshold (biothesiometry), intensity of pain, sensory function, co-ordination, and reflex responses. Patients treated with the 'new formulation' or 'old formulation' showed significant improvement in the primary efficacy endpoint (vibration perception threshold at the big toe) and secondary efficacy endpoints in comparison to placebo. The active treatment groups were comparable to placebo in terms of safety. A specific vitamin B complex (with and without folic acid) significantly improved symptoms of alcoholic polyneuropathy over a 12-week treatment period.


Recovery after fracture of the distal radius.
Stretching exercises are an important part of recovery after sustaining a fracture of the distal radius. However, from the patient's perspective, painful stretching exercises can be counterintuitive after injury. Stretching exercises are straightforward and do not require a significant amount of coaching. It is ultimately the protectiveness, passivity, and sometimes a sense of futility that require coaching. The key for the provider is to empathize with the difficult and counterintuitive nature of the recovery process.


Effect of temperature on [3H]ryanodine binding to sarcoplasmic reticulum from bullfrog skeletal muscle.
It has been clarified that ryanodine binds to Ca2(+)-induced Ca release channels in the open state in sarcoplasmic reticulum. While the pharmacological action of ryanodine is known to be retarded at a low temperature, the Ca-releasing action of caffeine is potentiated at a low temperature. In order to obtain deeper insight into the molecular mechanism underlying Ca-release, the effect of temperature on ryanodine binding to the heavy fraction of sarcoplasmic reticulum (HFSR) from bullfrog skeletal muscle was examined. Although Ca2+ is indispensable for ryanodine binding, Ca2+ alone cannot cause ryanodine binding in a reaction medium of a salt concentration similar to that of the sarcoplasm. In addition to Ca2+, caffeine and/or beta,gamma-methylene adenosine triphosphate (AMPOPCP) are necessary. [3H]Ryanodine binding at 25 degrees C closely paralleled the Ca release activity in respect of the Ca2(+)-dependence in the presence of caffeine and/or AMPOPCP, and the effects of inhibitors. A Scatchard plot for ryanodine binding gave a straight linear line, indicating a single class of homogeneous binding sites. At 0 degrees C, the rate of ryanodine binding decreased. Q10 being about 3 on average. The affinity for ryanodine was reduced to about half that at 25 degrees C, with no change in the maximum number of binding sites. The temperature-dependent change in apparent affinity for Ca2+ on ryanodine binding is not always consistent with that in the case of Ca-release activity. The bound ryanodine may be in an occluded state because it did not dissociate for up to 90 h at 0 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)


Preface.
This volume was inspired by the topics presented at the international conference "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in Będlewo, Poland. System biology is an approach which tries to understand how micro systems, at the molecular and cellular levels, affect macro systems such as organs, tissue and populations. Thus it is not surprising that a major theme of this volume evolves around cancer and its treatment. Articles on this topic include models for tumor induced angiogenesis, without and with delays, metastatic niche of the bone marrow, drug resistance and metronomic chemotherapy, and virotherapy of glioma. Methods range from dynamical systems to optimal control. Another well represented topic of this volume is mathematical modeling in epidemiology. Mathematical approaches to modeling and control of more specific diseases like malaria, Ebola or human papillomavirus are discussed as well as a more general approaches to the SEIR, and even more general class of models in epidemiology, by using the tools of optimal control and optimization. The volume also brings up challenges in mathematical modeling of other diseases such as tuberculosis. Partial differential equations combined with numerical approaches are becoming important tools in modeling not only tumor growth and treatment, but also other diseases, such as fibrosis of the liver, and atherosclerosis and its associated blood flow dynamics, and our volume presents a state of the art approach on these topics. Understanding mathematics behind the cell motion, appearance of the special patterns in various cell populations, and age structured mutations are among topics addressed inour volume. A spatio-temporal models of synthetic genetic oscillators brings the analysis to the gene level which is the focus of much of current biological research. Mathematics can help biologists to explain the collective behavior of bacterial, a topic that is also presented here. Finally some more across the discipline topics are being addresses, which can appear as a challenge in studying problems in systems biology on all, macro, meso and micro levels. They include numerical approaches to stochastic wave equation arising in modeling Brownian motion, discrete velocity models, many particle approximations as well as very important aspect on the connection between discrete measurement and the construction of the models for various phenomena, particularly the one involving delays. With the variety of biological topics and their mathematical approaches we very much hope that the reader of the Mathematical Biosciences and Engineering will find this volume interesting and inspirational for their own research.


The potential effects of radiographic criteria to exclude aortography in patients with blunt chest trauma. Results of a study of 32 patients with proved aortic or brachiocephalic arterial injury.
The purpose of this study was to test the effectiveness, in patients with known aortic or brachiocephalic arterial injury, of five previously published radiographic criteria for excluding aortography in patients with blunt chest trauma. These criteria were (1) normal findings on erect chest radiograph; (2) normal aortic arch and left subclavian artery; (3) normal aortic arch, descending aorta, aortopulmonary window, tracheal position, and left paraspinal interface; (4) normal right paratracheal stripe and nasogastric tube position, and (5) normal aortic arch and tracheal and nasogastric tube position. One or more of these criteria were met in 6% to 25% of patient with major thoracic arterial injury, depending on the criteria used. Interestingly, two (6%) patients had radiographs that showed no specific signs of mediastinal hemorrhage, which indicates that the chest radiograph is limited in its sensitivity to detect major thoracic arterial injury. Because of these results, we do not believe that attempts to limit aortography in patients with supine film evidence of mediastinal abnormality, based on the absence of certain signs of mediastinal hemorrhage, are warranted. Furthermore, an abnormal radiograph cannot be relied on as the sole criterion for aortography if the goal of care is to detect as close to 100% of vascular injuries as possible.


New horizons in the development of antiepileptic drugs: the search for new targets.
The past decades have brought many advances to the treatment of epilepsy. However, despite the continued development and release of new antiepileptic drugs, many patients have seizures that do not respond to drug therapy or have related side effects that preclude continued use. Even in patients in whom pharmacotherapy is efficacious, current antiepileptic drugs do not seem to affect the progression or underlying natural history of epilepsy. Furthermore, there is currently no drug available which prevents the development of epilepsy, e.g., after head trauma or stroke. Thus, there are at least three important goals for the future: (1) better understanding of processes leading to epilepsy, thus allowing to create therapies aimed at the prevention of epilepsy in patients at risk; (2) development of disease-modifying therapies, interfering with progression of epilepsy, and (3) improved understanding of neurobiological mechanisms of pharmacoresistance, allowing to develop drugs for reversal or prevention of drug resistance. The Second Workshop on New Horizons in the Development of Antiepileptic Drugs explored these three goals for improved epilepsy therapy, with a focus on the search for new drug targets for prevention of epilepsy, for interfering with progression of epilepsy, and for interfering with drug resistance in epilepsy. A special topic dealt with gene expression analysis for target identification. Furthermore, pharmacological and non-pharmacological targets for curing epilepsy were explored. In this conference review, the current status of antiepileptic therapies is critically assessed, and innovative approaches for future therapies are highlighted.


Screening workers exposed to 4,4'-methylenebis(2-chloroaniline) for bladder cancer by cystoscopy.
A bladder cancer incidence study was conducted among 540 workers exposed to the potential bladder carcinogen 4,4'-methylenebis(2-chloroaniline) from 1969 to 1979. Among the 385 workers who participated in a urine screening examination, none had suspicious or positive cytology. Twenty-one workers had at least one reading of atypia and 60 had either a positive dipstick for heme or greater than five red blood cells per low power field. The study protocol initially involved referral to private physicians for follow-up of any suspicious laboratory results. However, the diagnosis by cystoscopy of a bladder tumor in a nonsmoking man less than 30 years old with low-level hematuria prompted us to offer cystoscopy to all members of the cohort. A total of three tumors were identified in 200 persons who received cystoscopy. All were low-grade, papillary tumors and two occurred in men with completely normal urine screening results. These findings suggest that cystoscopy of asymptomatic persons should be considered in designing bladder cancer screening programs in high-risk cohorts.


Pyrosequencing of TPMT alleles in a general Swedish population and in patients with inflammatory bowel disease.
Interindividual differences in therapeutic efficacy in patients treated with thiopurines might be explained by the presence of thiopurine S-methyltransferase (TPMT) alleles that encode for reduced TPMT enzymatic activity. It is therefore of value to know an individual's inherent capacity to express TPMT. We developed a pyrosequencing method to detect 10 single-nucleotide polymorphisms (SNPs) in TPMT. A Swedish population (n = 800) was examined for TPMT*3A, TPMT*3B, TPMT*3C, and TPMT*2. Patients with inflammatory bowel disease (n = 24) and healthy volunteers (n = 6), selected on the basis of TPMT enzymatic activity, were investigated for all 10 SNPs to determine the relationship between TPMT genotype and phenotype. In the general population we identified the following genotypes with nonfunctional alleles: TPMT*1/*3A (*3A allelic frequency, 3.75%), TPMT*1/*3C (*3C allelic frequency, 0.44%), TPMT*1/*3B (*3B allelic frequency, 0.13%), and TPMT*1/*2 (*2 allelic frequency, 0.06%). All nine individuals with normal enzymatic activity were wild-type TPMT*1/*1. Thirteen individuals with intermediate activity were either TPMT*1/*3A (n = 12) or TPMT*1/*2 (n = 1). Eight individuals with low enzymatic activity were TPMT*3A/*3A (n = 4), TPMT*3A/*3C (n = 2), or TPMT*1/*3A (n = 2). Next to wild type, the most frequent alleles in Sweden are TPMT*3A and TPMT*3C. A previously established phenotypic cutoff for distinguishing normal from intermediate metabolizers was confirmed. To identify the majority of cases (90%) with low or intermediate TPMT activity, it was sufficient to analyze individuals for only 3 of the 10 SNPs investigated. Nevertheless, this investigation indicates that other mutations might be of relevance for decreased enzymatic activity.


Extracellular matrix regulates proliferation and phospholipid turnover in glomerular epithelial cells.
To understand how glomerular epithelial cell (GEC) growth might be regulated in health and disease, we studied the effects of growth factors and extracellular matrix on proliferation and membrane phospholipid turnover in cultured rat GECs. In GECs adherent to type I collagen matrix, epidermal growth factor (EGF), insulin, and serum stimulated DNA synthesis and increased cell number. In addition, GECs proliferated when adherent to type IV collagen, but not to laminin or plastic substrata. Attachment of GECs to the substrata that facilitated proliferation (types I or IV collagen) produced increases in 1,2-diacylglycerol (DAG), an activator of protein kinase C (PKC). Increased DAG was associated with hydrolysis of inositol phospholipids and an increase in inositol trisphosphate and was not dependent on the presence of growth factors. After PKC downregulation (by preincubation with a high dose of phorbol myristate acetate), DNA synthesis was enhanced in GECs adherent to collagen. Thus contact of GECs with collagen matrices is required for serum, EGF, or insulin to induce proliferation. Collagen matrix also activates phospholipase C. As a result, the DAG-PKC signaling pathway desensitizes GECs to the mitogenic effects of growth factors and might promote cell differentiation. Understanding the interaction between GECs, growth factors, and extracellular matrix may elucidate the mechanisms of proliferation during glomerular injury.


Changes in otological teaching following analysis of failures in surgical technique.
An analysis was made of the results of mastoid surgery performed in the Professorial Unit of the Royal National Throat, Nose and Ear Hospital, London, between the years 1970 and 1974. Most of the surgery was performed by trainee surgeons at the end of the teaching programme. The incidence of unsatisfactory results was greater with open mastoid surgery than with closed mastoid surgery. The causes of failure were analysed, and the underlying defects in the teaching programme identified. The subsequent modification in the teaching methods that resulted are illustrated.


Seasonal variations in urinary excretion of calcium and oxalate in normal subjects in patients with idiopathic hyperclaciuria.
A longitudinal 9-year retrospective study of 24-hour urinary calcium values has been made in a metabolic stone clinic amongst patients with idiopathic hypercalciuria. No seasonal variations could be observed in contrast ot a previous study from Leeds, A prospective longitudinal study was made of 24-hour urinary calcium values in a small group of normal subjects. No seasonal variation could be ovserved. In the prospective study no seasonal variations in urinary oxalate could be observed. In a 2-year longitudinal study of stone patients with idiopathic hypercalciuria, urinary oxalate was found to be higher in the summer than in the winter. This was attributed to the combination of a higher intake of oxalate-rich foods in the summer, and the low calcium diet with which they were treated.


An unusual infection in an injecting drug user.
Injecting drug users are prone to atypical infections. We present a case of septic thrombophlebitis secondary to Fusobacterium gonidiaformans infection in a heroin user, which demonstrates the frequently unusual nature of pathogens and presentations in this group of patients.


Prospective Validation of the Chinese Version of the Self-Efficacy for Exercise Scale Among Middle-Aged Patients With Coronary Heart Disease.
The aim of this study was to further evaluate the psychometric properties of the Chinese version of the Self-Efficacy for Exercise Scale (SEE-C) among middle-aged outpatients with coronary heart disease (CHD). Psychometric evaluation design. A convenience sample of 355 CHD patients was recruited and followed up at 3 and 6 months. Cronbach's alpha, construct validity (exploratory factor analysis), and concurrent and predictive validity were examined. The SEE-C had a single-factor structure that was stable over time and had high internal consistency. Baseline SEE-C scores were significantly and positively associated with quality of life and total exercise time per week and significantly and negatively associated with anxiety and depression. They also significantly predicted total exercise per week at the 3- and 6-month follow-ups. The SEE-C is a robust, reliable, and valid measure of exercise self-efficacy for middle-aged Chinese CHD outpatients. The SEE-C can assess patients' exercise self-efficacy, so that appropriate interventions to improve exercise self-efficacy can be provided.


A multi-model deep convolutional neural network for automatic hippocampus segmentation and classification in Alzheimer's disease.
Alzheimer's disease (AD) is a progressive and irreversible brain degenerative disorder. Mild cognitive impairment (MCI) is a clinical precursor of AD. Although some treatments can delay its progression, no effective cures are available for AD. Accurate early-stage diagnosis of AD is vital for the prevention and intervention of the disease progression. Hippocampus is one of the first affected brain regions in AD. To help AD diagnosis, the shape and volume of the hippocampus are often measured using structural magnetic resonance imaging (MRI). However, these features encode limited information and may suffer from segmentation errors. Additionally, the extraction of these features is independent of the classification model, which could result in sub-optimal performance. In this study, we propose a multi-model deep learning framework based on convolutional neural network (CNN) for joint automatic hippocampal segmentation and AD classification using structural MRI data. Firstly, a multi-task deep CNN model is constructed for jointly learning hippocampal segmentation and disease classification. Then, we construct a 3D Densely Connected Convolutional Networks (3D DenseNet) to learn features of the 3D patches extracted based on the hippocampal segmentation results for the classification task. Finally, the learned features from the multi-task CNN and DenseNet models are combined to classify disease status. Our method is evaluated on the baseline T1-weighted structural MRI data collected from 97 AD, 233 MCI, 119 Normal Control (NC) subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The proposed method achieves a dice similarity coefficient of 87.0% for hippocampal segmentation. In addition, the proposed method achieves an accuracy of 88.9% and an AUC (area under the ROC curve) of 92.5% for classifying AD vs. NC subjects, and an accuracy of 76.2% and an AUC of 77.5% for classifying MCI vs. NC subjects. Our empirical study also demonstrates that the proposed multi-model method outperforms the single-model methods and several other competing methods.


Chemokine induction by HIV-1: recruitment to the cause.
Immunomodulation frequently occurs during viral infections; the mechanisms of which are continually being defined at the cellular and tissue levels. Recently, a study of the effects of HIV-1 on dendritic cells (DCs) identified inflammatory chemokines as highly upregulated during HIV-1 infection and during viral Tat expression in monocyte-derived DCs. It is becoming increasingly clear that HIV-1 has evolved multiple strategies to ensure the maintenance of a local pool of susceptible cells for additional rounds of virus replication.


Systemic immunologic stimuli increase class I and II antigen expression in mouse kidney.
The effect of systemic immunologic stimulation on renal expression of the H-2K (class I) and Ia (class II) antigens of the mouse major histocompatibility complex was explored. We previously reported that graft-vs-host (GvH) disease in mice caused an increase in host renal Ia expression. In the present experiments, we demonstrated that Kk antigen expression also increased during GvH. Other immune stimuli (allogeneic tumor grafts or injections of allogeneic spleen cells) caused increased renal Ia (and, where studied, Kk) expression in the epithelium of some renal tubules, as demonstrated by indirect immunofluorescence (IIF) or immunoperoxidase (IIP) staining. The normal interstitial Ia staining was frequently diminished in the kidneys of mice given these stimuli. At least in the case of allogeneic tumor grafts, the changes in renal Ia and H-2K were dependent on host T cells, in that no similar change appeared in nude (nu/nu) mice bearing allogeneic tumor grafts. By histochemical techniques, most of the change was in proximal tubules. In semiquantitative absorption, the total renal Ia was usually increased (two- to 20-fold) in parallel with the IIF or IIP changes. Serial studies revealed that MHC product induction was frequently transient and was not associated with detectable histologic abnormalities. In cultured renal cells, increased Iak and Kk could be demonstrated by IIF after 4 days of culture in supernatants of lymphocytes stimulated with concanavalin A: the activity in these supernatants was probably not interleukin 2, but might have been IFN-gamma, because IFN-gamma also induced this change. We conclude that systemic immunologic stimuli alter MHC product expression in renal tubule epithelium and that this effect can be stimulated in vitro by supernatants of stimulated lymphocytes.


Fungal biosynthesis of endochitinase and chitobiase in solid state fermentation and their application for the production of N-acetyl-D-glucosamine from colloidal chitin.
The present study was directed to the production of N-acetyl-D-glucosamine using endochitinase and chitobiase from fungal cultures in solid culturing. Fifteen fungal strains were evaluated for endochitinase and chitobiase production under solid-state fermentation using agro-industrial residues, of which Penicillium aculeatum NRRL 2129 showed maximum endochitinase activity whereas Trichoderma harzianum TUBF 927 showed maximum chitobiase activity. Eleven substrates, alone and in combination with chitin, were evaluated for the enzyme production. Optimization of physico-chemical parameters such as incubation period and initial moisture content, and nutritional parameters such as chitin source, inorganic and organic nitrogen sources, were carried out. Optimization resulted in more than 3-fold increase in endochitinase production (from 3.5 to 12.53 U/g dry weight of substrate) and about 1.5-fold increase in chitobiase production (from 1.6 to 2.25 U/g dry weight of substrate). Studies on the degradation of colloidal chitin to N-acetyl-D-glucosamine showed improved efficiency when endochitinase and chitobiase were used in combination.


The ACTH(4-9) analog ORG 2766 and recovery after brain damage in animal models--a review.
Treatment with adrenocorticotrophic hormone (ACTH), as well as with ACTH fragments and analogues, can influence behaviour of animals and humans. Furthermore it facilitates recovery of damaged peripheral nervous tissue. The question whether ACTH/MSH peptides affect recovery processes after injury to the central nervous system as well is addressed in the present review. The effects of administration of the ACTH(4-9) analog ORG 2766 after brain lesions has been studied frequently. However, the interpretation of the available data is confused by the variability of the results. Several factors can be identified which influence the efficacy of the peptide: (i) not all behavioural tests are equally suitable to reveal a peptide effect on behavioural recovery; (ii) the affected brain area; (iii) whether cell bodies or terminals are affected; (iv) the post-operative housing conditions; and (v) the onset and duration of peptide administration. Two possible explanations of peptide efficacy on functional recovery are considered: first, the peptide may accelerate spontaneously occurring recovery processes and second, the peptide may induce compensatory mechanisms underlying functional recovery without recuperation of the damaged neurons. These compensatory mechanisms seem to rely mainly on enhanced non-selective attention by activation of limbic structures. It is as yet unknown to which receptor system ORG 2766 binds; the analog lacks affinity for the known melanocortin (MC) receptors in brain, yet ORG 2766 is able to modulate the activity of endogenous opioids and the NMDA-receptor. A modulating influence of the peptide on NMDA-receptor activity might indirectly account for both enhanced attention--with ensuing behavioural recovery--and the acceleration of spontaneous recovery.


Further insight into the heparin-releasable and glycosylphosphatidylinositol-lipid--anchored forms of tissue factor pathway inhibitor.
The release of tissue factor pathway inhibitor (TFPI) from human umbilical vein endothelial cells (HUVECs) was investigated using heparin and phospholipase C. The experiment included incubating HUVECs with 0, 1, or 10 U/mL heparin diluted in Dulbecco Modified Eagle's Medium plus 5% fetal calf serum for 1 or 24 hours. A statistically significant increase in TFPI activity levels was seen at 1 hour, but not at 24 hours. A 20-fold increase in the release of TFPI after phospholipase C treatment of HUVECs was demonstrated, confirming that it is glycosylphosphatidylinositol-lipid (GPI) anchored. Sequential treatment of HUVECs with phospholipase C and heparin was performed, and a trend was observed where GPI-anchored TFPI levels were increased after 1 hour of pretreatment with heparin but were decreased after 24 hours. Serum is a requirement for the heparin-dependent release of TFPI from HUVECs. Heparin pretreatment of HUVECs may affect levels of GPI anchored TFPI in a time and dose-dependent manner.


Temporary or permanent support and replacement of cardiac function.
Cardiac assist devices are classified into the traditional engineering categories of displacement and rotary pumps. Clinical use and indications of the various pump categories are outlined and a detailed description of the currently available systems is given. The first section deals with extracorporeal as well as implantable ventricular assist devices of the displacement type and is followed by a section on current developments in the field of total artificial hearts. The latter part of the article covers the rotary pump category from cardiopulmonary bypass applications to implantable systems, including specific design aspects of radial, diagonal and axial pumps.


Compensatory pituitary-thyroid mechanisms in major depressive disorder.
The thyrotropin-releasing hormone (TRH) stimulation test was administered to 47 patients meeting DSM-III criteria for major depressive disorder (with melancholia) and to 19 nondepressed patients. The wide variability of pituitary responses to TRH stimulation noted in the depressed patients provides evidence for the dysregulation of compensatory hypothalamic-pituitary-thyroid function in acute depression. Blunted thyroid-stimulating hormone (TSH) responses to TRH injection were found in 16 depressed (34%) and no nondepressed patients (p less than 0.01). Depressed patients who revealed blunted TSH responses also had blunted prolactin responses to TRH relative to other depressed and nondepressed patient groups (p less than 0.01). These patients (with blunted TSH and prolactin responses) may represent a psychobiologically distinct subgroup of endogenously depressed patients. Augmented (high normal) TSH responses to TRH stimulation were found in eight depressed patients (all women), in contrast to no nondepressed patients. These patients may have a subtle thyroidal dysfunction affecting the underlying endogenous depressive diathesis.


Evaluation of Turmeric Chip Compared with Chlorhexidine Chip as a Local Drug Delivery Agent in the Treatment of Chronic Periodontitis: A Split Mouth Randomized Controlled Clinical Trial.
The aim of this study was to evaluate and compare the effect of chlorhexidine (CHX) chip and turmeric chip as a local drug delivery (LDD) agent in the treatment of patients with chronic periodontitis. A total of 120 sites with pocket depths 5-8 mm were chosen as a split mouth design at 3 sites in the same patient. Selected sites were randomly divided into three groups to receive CHX chip in addition to scaling and root planing (SRP) in group A, turmeric chip in addition to SRP in group B, and SRP only in group C. Clinical parameters, that is, plaque index (PI), gingival index (GI), probing pocket depth (PPD), and relative attachment level (RAL) were recorded at baseline, 1 month, and 3 months interval. On applying statistical analysis, results revealed that there was a significant reduction in all the clinical parameters, that is, PI, GI, PPD, and gain in RAL from baseline to 1 month and 3 months in all the three groups. These results were found to be significantly high in the CHX group and turmeric group than in the SRP group. Also, the results in both the test groups were maintained till the end of the study periods, but SRP group showed a significant deterioration after 1 month as was seen by increase in PPD and decrease in RAL scores after 3 months in the SRP group. Both the treatment modalities with the application of LDD as an adjunct to SRP proved to be equally beneficial in the treatment of chronic periodontitis.


CD1 expression is not affected by human peptide transporter deficiency.
Conventional major histocompatibility complex class I molecules are highly polymorphic and present peptides to cytotoxic T cells. These peptides derive from the proteolytic degradation of endogenous proteins in the cytosol and are translocated into the endoplasmic reticulum by a peptide transporter consisting of two transporter associated with antigen processing (TAP) molecules. Absence of this transporter leads to the synthesis of unstable peptide free class I molecules that are weakly expressed on the cell surface. Mouse nonconventional class I molecules (class Ib) may also present TAP-dependent peptides. In humans, CD1 antigens are nonconventional class I molecules. Recently, we characterized a human HLA class I deficiency resulting from a homozygous TAP deficiency. We show here that CD1a and -c are normally expressed on epidermal Langerhans cells of the TAP-deficient patients, as are CD1a, -b, and -c on dendritic cells differentiated in vitro from monocytes. Moreover, the CD1a antigens present on the surface of the dendritic cells are functional, since they internalize by receptor-mediated endocytosis gold-labeled F(ab')2 fragments of an anti-CD1a mAb. This suggests either that CD1 molecules are empty molecules, that they are more stable than empty conventional class I proteins, or that CD1 molecules present TAP-independent peptides.


Biomimetic Decoy Inhibits Tumor Growth and Lung Metastasis by Reversing the Drawbacks of Sonodynamic Therapy.
Sonodynamic therapy (SDT) shows tremendous potential to induce immunogenic cell death (ICD) and activate antitumor immunity. However, it can aggravate hypoxia and release platelet (PLT)-associated danger-associated molecular patterns (DAMPs), which impede therapeutic efficacy and promote tumor metastasis. In order to solve these problems, a biomimetic decoy (designated as Lipo-Ce6/TPZ@MH ) is constructed to reverse the drawbacks of SDT by loading sonosensitizer chlorin e6 (Ce6) and hypoxia-activated tirapazamine (TPZ) in the red blood cells-PLTs hybrid membrane (MH )-camouflaged pH-sensitive liposome. After administration, the decoy exhibits enhanced cancer accumulation and retention abilities due to the immune escape and specific targeting behaviors by biomimetic surface coating. Upon local ultrasound, Ce6 produces toxic reactive oxygen species for SDT, and the resulting hypoxia microenvironment activates TPZ, which can realize a high-effective synergistic therapy. Meanwhile, DAMPs-mediated tumor metastasis is significantly inhibited, because the decoy retains platelet binding functions but is incapable of platelet-mediated metastasis. In addition, ICD-mediated strong antitumor immunities further prevent the growth and metastasis of the residual tumors left behind after synergistic treatment. Taken together, this study highlights the potential of using this cascade therapeutic therapy plus biomemitic decoy in one nanosystem to both eliminate melanoma in situ and suppress lung metastasis.


Does the membrane potential control incorporation of tubulovesicles into the secreting apical membrane of the rat parietal cell?
The present studies were designed to examine the effect of changes in membrane potential by means of protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) and variations in the pH of the medium on the secretory response of parietal cells. Studies were performed in vitro using isolated cells from rat stomachs and acid production was indirectly determined by 14C-aminopyrine (AP) accumulation. CCCP affected both basal and histamine-stimulated AP accumulation in a concentration-dependent manner. The AP accumulation ratios depended on pH of the incubation medium; the ratio was lowest at pH 6.6, and increased progressively as the pH of the medium increased to 7.8. Moreover, the decreases in AP accumulation ratios caused by simultaneous addition of CCCP and AP to cell suspensions compared to those in which CCCP was added to incubated cells after achieving the steady-state of AP accumulation were quantitatively similar. These findings suggest that the decrease in AP accumulation due to CCCP treatment is a consequence of an activation of acid secretion rather than an inhibitor of acid production. From the present and previously published data, we propose a working hypothesis: membrane recycling is dependent on changes in apical membrane potential.


Acute pancreatitis associated with acute hepatitis A in a young child.
Acute hepatitis A infection is an unusual cause of pancreatitis in adults and has not been reported previously in young children. We describe a 4-year-old girl with acute pancreatitis associated with hepatitis A infection.


Patient expectations in internet-based self-help for social anxiety.
A number of controlled trials have demonstrated the efficacy of Internet-based cognitive-behaviour therapy for treating social anxiety disorder (SAD). However, little is known about what makes those interventions work. The current trial focuses on patient expectations as one common mechanism of change. The study examines whether patients' expectancy predicts outcome, adherence, and dropout in an unguided Internet-based self-help programme for SAD. Data of 109 participants in a 10-week self-help programme for SAD were analysed. Social anxiety measures were administered prior to the intervention, at week 2, and after the intervention. Expectancy was assessed at week 2. Patient expectations were a significant predictor of change in social anxiety (β = - .35 to - .40, all p < .003). Patient expectations also predicted treatment adherence (β = .27, p = .02). Patients with higher expectations showed more adherence and better outcome. Dropout was not predicted by expectations. The effect of positive expectations on outcome was mediated by early symptom change (from week 0 to week 2). Results suggest that positive outcome expectations have a beneficial effect on outcome in Internet-based self-help for SAD. Furthermore, patient expectations as early process predictors could be used to inform therapeutic decisions such as stepping up patients to guided or face-to-face treatment options.


GDP and AGE receptors: mechanisms of peritoneal damage.
Long-term peritoneal dialysis (PD) is limited by morphological changes of the peritoneal membrane. Structural changes were promoted by toxicity of glucose degradation products (GDPs) which are generated during heat sterilization in peritoneal dialysis fluids (PDFs). Besides their direct toxicity GDPs promote formation of advanced glycation endproducts (AGEs). RAGE (receptor for AGE) is the best characterized signal transduction receptor for AGEs and is expressed on mesothelial cells. The effects of PDFs with different amounts of GDPs were compared on morphological changes in the peritoneal membrane in a RAGE -/- mouse model. It could be demonstrated that RAGE plays a pivotal role in structural damage (e.g. inflammation, neoangiogenesis and fibrosis) of the peritoneal membrane. Further investigations of this pathway with regard to preventing peritoneal fibrosis should be performed to maintain the integrity of the peritoneal membrane in peritoneal dialysis patients.


Results of long-term follow-up after compensated fixed-dose therapy for thyrotoxicosis.
To evaluate the effects of simple compensated fixed-dose iodine-131 therapy for thyrotoxicosis, the long-term results for 74 patients treated with a fixed dose of iodine-131 ranging from 5 to 12 mCi (185 to 444 MBq) were evaluated in the first 2 years of a trial. The dose selected was loosely based on the gross size of the thyroid gland. Routine antithyroid drug therapy was given for a minimum of 3 months after iodine-131 therapy. The mean (+/- SD) duration of follow-up was 74.5 +/- 42 months. The results indicated that roughly 25% of patients treated in this way will become hypothyroid after 5 years and that 85% are cured (need no further therapy during the follow-up period) using a single dose of iodine-131. Of those cured using a single iodine-131 dose, 81% were no longer receiving drugs after 6 months and 85% after 1 year. Such a regimen seems currently to be among the best available where prolonged periods of medication-free euthyroidism after therapy are sought.


Ground and excited state properties of photoactive platinum(IV) diazido complexes: theoretical considerations.
Recently synthesized by the group of Sadler, the platinum(IV) diazido complexes [Pt(N(3))(2)(OH)(2)(L')(L'')] (L' and L'' are N-donor ligands) have potential to be used as photoactivatable metallodrugs in cancer chemotherapy. In the present study optimized structures and UV-Vis electronic spectra of trans,trans,trans- and cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))(2)] (1t and 1c, respectively) as well as cis,trans,cis-[Pt(N(3))(2)(OH)(2)(L)(2)] (L = NH(3), NH(2)CH(3), NF(3), PH(3), PF(3), H(2)O, CO, OH(-), CN(-), py, imid; 2c-11c) and cis,trans-[Pt(N(3))(2)(OH)(2)(bpy)] (12c) complexes were predicted using density functional theory (DFT). The ground state electronic structures of all complexes were analyzed with the help of the natural bond orbital analysis (NBO). The electronic spectra of 1c and 1t were computed using time-dependent density functional theory (TDDFT) with five different density functionals and the ab initio CASSCF/CASPT2 method (for the five lowest energy transitions). The best agreement with available experiments was found in the case of the long-range corrected ωB97X functional. The electronic transitions were characterized by the analysis of the natural transition orbitals (NTO). The low-lying excited singlet states of 1t and 1c have significant azide-to-platinum(IV) charge-transfer character (LMCT). Geometry optimization of the three lowest singlet excited states performed using TDDFT results in the simultaneous dissociation of two azide ligands with the formation of the azidyl radicals N(3)˙ and photoreduction of Pt(IV) to Pt(II). Variation of the ligand L does not strongly affect the nature and the relative energies of the low-lying states. It is shown that the replacement of the OH(-) groups in 1c by OPh(-) ligands results in the red shift of the intense N(3)(-)→Pt LMCT band and the appearance of transitions with significant intensity in the visible region of the spectrum. The dissociative nature of the low-lying unoccupied orbitals remains unaffected. These theoretical results may suggest new experimental routes for the improvement of the photochemical activity of Pt(IV) diazido complexes.


Mutations in the Notch pathway alter the patterning of multifidus.
Clinical studies have suggested that defects in the epaxial muscles, particularly multifidus, may contribute to the etiology of idiopathic scoliosis. While the epaxial muscles and the vertebrae derive from the same embryonic segmentation process, the mechanisms that pattern the multisegmental back muscles are still unclear. The process of segmentation is regulated by the Notch signaling pathway, and mutations in the modulators delta-like 3 (Dll3) and lunatic fringe (Lfng) are genetic models for spinal disorders such as scoliosis. Osteological defects have been characterized in these genetic models, but myological phenotypes have not previously been studied. We analyzed the multifidus muscle in the mouse (Mus musculus) and observed intriguing changes in the cranio-caudal borders of multifidus in Dll3 and Lfng models. Statistical analysis did not find a significant association between the majority of the multifidus anomalies and the vertebral defects, suggesting a previously unappreciated role for Notch signaling in patterning epaxial muscle groups. These findings indicate an additional mechanism by which DLL3 and LFNG may play a role in the etiology of human idiopathic scoliosis.


Elevated erythrocyte aggregation in patients with central retinal vein occlusion and without conventional risk factors.
Retinal venous circulation is characterized by the combination of a low flow state and a high vascular resistance, which would make it particularly dependent on blood viscosity. Erythrocyte aggregation is the chief determinant of blood viscosity at low shear rates. Recent studies have demonstrated increased erythrocyte aggregation in many systemic vascular disorders and also in retinal vein occlusion. To assess the possible role of abnormal hemorheologic findings in the pathogenesis of central retinal vein occlusion (CRVO), the authors retrospectively studied erythrocyte aggregation and hematocrit and fibrinogen levels in 33 patients with CRVO and without any known risk factors (diabetes, hypertension, smoking, hyperlipidemia, cardiovascular disease, glaucoma). Erythrocyte aggregation was assessed with a light back-scattering method. Results were compared with those of a group of 33 age- and sex-matched controls. Eleven (33%) of the 33 patients with CRVO had abnormal hemorheologic findings. Erythrocyte aggregation was highly significantly increased in the CRVO group when compared with the control group (P < 0.0001), as was the hematocrit level (P < 0.05). In addition, the proportion of patients with abnormal blood rheologic tests was greater (50%) in the subgroup of patients who initially had nonischemic CRVO that worsened into an ischemic CRVO during the follow-up. These data suggest that abnormal hemorheologic findings could affect the pathogenesis of CRVO, and perhaps be predictive of an aggravation. The latter hypothesis needs to be confirmed in a larger, prospective study.


COP-coated vesicles in intracellular protein transport.
COP-coated vesicles have originally been implicated in vesicular transport between subcompartments of the Golgi complex in mammals in a cis to trans direction. More recently, a role for COP-coated vesicles in transport between the endoplasmic reticulum (ER) and Golgi in mammalian cells has been proposed. Under certain conditions COP-coats have been localized to special domains of the transitional ER and to the cis side of the Golgi complex. This led to the assumption that COP-coated vesicles are involved in export of proteins from the ER. In addition, new findings point to a function of COP-coated vesicles in back transport of proteins from the Golgi to the ER. At present it is not known whether COP-coated vesicles move only in one or in both directions between ER and Golgi.


[Profile of telomerase and telomerase RNA expression in nasopharyngeal carcinogenesis of rats induced by N, N'dinitrosopiperazine (DNP)].
To investigate the profile of telomerase and telomerase RNA expression in nasopharyngeal carcinogenesis (NPC) induced by N, N'dinitrosopiperazine (DNP) and examined histolofically. Nasopharyngeal carcinomas of rats were induced by DNP and examined histologically. PCR-ELISA and nested RT-PCR were used to assay telomerase and telomerase RNA expression at different stages in the nasopharyngeal tissues of rats. During the carcinogenesis process, telomerase activity increased along with the formation of a nasopharyngeal carcinoma. Telomerase expression was positively related with nasopharyngeal carcinogenesis. Telomerase RNA expression was present and did not change during the NPC process. Expression of telomease RNA was earlier than telomerase activation. Telomerase activation and telomerase RNA expressin were also detected in the pre-cancerous nasopharyngeal lesions. Telomerase activation may participate in the onset and progression of NPC, and is an early step in NPC.


[Synchronous primary lung cancers: due to the four cases].
If two primary lung cancers are present in the same time, it diagnosed as synchronous lung cancer. It constitutes 0.1-1.6% of all lung cancers. In this report, we described four cases diagnosed synchronous multiple primary lung cancers (MPLC) in between June 1999 and May 2002. Mean age was 63, and all of those were male. All patients were heavy smoker (mean 58 packet/year). Histology of lung cancers was squamous-adeno in two cases, squamous-small cell lung cancer in one case, and squamous-squamous in two cases. All patients had bilateral mass lesions and no mediastinal and systemic spread. Lesion of second primary lung cancer was unable to seen in two patient's chest X-ray. Their lesions were seen by computerized tomography in one case, and by bronchoscope only in the other case. Lesion site was left lower lobe, right lower lobe, right middle lobe, and left upper lobe (25% for each). Diagnosis of lung cancer was made by transthoracic needle biopsy in three lesion, and made by bronchoscopic biopsy in other lesions. While it is recommended that, all of MPLC lesions were staged separately and treated surgically, due to the advanced age, presence of small cell lung cancer, and inadequate post-operative respiratory reserve, surgical treatment could not apply to these patients and they received chemotherapy. Three of them was died (mean survival was 11 months). Due to the this report, we emphasized that diagnostic procedures should be done separately for each lesions in patients who had more than one lesion, and treatment should plane according to these results.


Kinematics of treadmill versus overground locomotion in horses.
A kinematic analysis was carried out to compare treadmill and overground locomotion in horses at the trot. Stride variables and limb and trunk movements of 10 Dutch Warmblood horses were measured using the CODA-3 gait analysis system. Overground recordings were made on a rubber ground surface and on an asphalt track. Treadmill recordings were taken after a controlled habituation programme and at the same velocities as measured overground. On asphalt, a shorthened stride duration and a decreased vertical displacement of the withers were found compared with those on rubber ground. On the treadmill, stance duration of the forelimbs was longer than for either overground condition. Correspondingly, the hind limbs were placed earlier than the forelimbs in making diagonal ground contact in overground locomotion, but this changed to preceding forelimbs on the treadmill. Both forelimbs and hind limbs were moved more caudally during the retraction phase on the treadmill, while no differences were found in the protraction angle. The vertical movement of the hooves as well as the withers was smaller on the treadmill than on rubber ground. Treadmill belt velocity decreased by 9% during the stance phase. This is supposed to be an important reason for the differences in biomechanics and kinematics between treadmill and overground locomotion, which must be kept in mind when data obtained during treadmill locomotion have to be extrapolated to overground conditions.


The use of contact lenses in low vision rehabilitation: optical and therapeutic applications.
Ocular pathology that manifests at an early age has the potential to alter the vision-dependent emmetropisation mechanism, which co-ordinates ocular growth throughout childhood. The disruption of this feedback mechanism in children with congenital or early-onset visual impairment often results in the development of significant ametropia, including high levels of spherical refractive error, astigmatism and anisometropia. This review examines the use of contact lenses as a refractive correction, low vision aid and therapeutic intervention in the rehabilitation of patients with bilateral, irreversible visual loss due to congenital ocular disease. The advantages and disadvantages of the use of contact lenses for increased magnification (telescopes and microscopes) or field expansion (reverse telescopes) are discussed, along with the benefits and practical considerations for the correction of pathological high myopia. The historical and present use of therapeutic tinted contact lenses to reduce photosensitivity and nystagmus in achromatopsia, albinism and aniridia are also presented, including clinical considerations for the contact lens practitioner. In addition to the known optical benefits in comparison to spectacles for high levels of ametropia (an improved field of view for myopes and fewer inherent oblique aberrations), contact lenses may be of significant psycho-social benefit for patients with low vision, due to enhanced cosmesis and reduced conspicuity and potential related effects of improved self-esteem and peer acceptance. The contact lens correction of patients with congenital vision impairment can be challenging for both practitioner and patient but should be considered as a potential optical or therapeutic solution in modern low vision rehabilitation.


Blood pressure-lowering drugs and secondary prevention of cardiovascular disease: systematic review and meta-analysis.
To systematically evaluate the efficacy of five commonly used blood pressure-lowering drugs in reducing cardiovascular events among patients with nonacute cardiovascular disease, but without heart failure. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials on 18 March 2017. The primary outcome was fatal and nonfatal cardiovascular events, and the secondary outcomes were all-cause death, fatal and nonfatal myocardial infarction, and stroke. Pooled risk ratios and corresponding 95% confidence intervals (CIs) were calculated using Mantel-Haenszel random-effects meta-analyses. Twenty-seven randomized controlled trials with 143 095 participants and a treatment duration of at least 12 months were included in our analyses. Fifteen trials enrolled patients with coronary artery disease, eight enrolled patients with cerebral artery disease, and four enrolled patients with cardiovascular disease. Of the 27 trials, 10 trials only included hypertensive patients. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs) (risk ratio 0.85, 95% CI 0.78-0.92), angiotensin receptor blockers (risk ratio 0.92, 95% CI 0.87-0.98), and diuretics (risk ratio 0.77, 95% CI 0.66-0.90) significantly reduced the risk of cardiovascular events. Apart from this, ACEIs significantly reduced all secondary outcomes, calcium channel blockers, and diuretics reduced stroke significantly. No significant difference was found in head-to-head comparisons of each given drug class with any other class. Although only ACEIs have evidences showing its effect in reducing cardiovascular events and all secondary outcomes, head-to-head comparisons did not provide strong evidence in difference in the effects between these blood pressure-lowering drugs.


Cost-effectiveness of screening for familial abdominal aortic aneurysms.
Screening for familial abdominal aortic aneurysms (AAA) is widely recommended. To analyze cost-effectiveness of screening for familial AAAs incremental cost-effectiveness (C/E) analysis based on an ultrasound screening among relatives and a decision model of screening program was compared to a baseline situation without systematic screening. 74% (238/322) of first-degree relatives of 150 consecutive AAA patients were screened at HUCH (Helsinki University Central Hospital). Effectiveness and costs of treatment were assessed using the Finnish Hospital Discharge Register and from survival analysis of 1130 AAA patients who underwent elective or emergency surgery in HUCH. To form incremental C/E-ratios the existing clinical practice was compared to a screening program for male siblings. Hypothetical screened and control cohorts of 1000 male relatives were used to create the decision model. Parameters in C/E-analyses were derived from our own data except for growth and rupture rates. A sensitivity analysis was carried out. The incremental effectiveness in life-years gained by the screening of male siblings was 92 years with incremental C/E-ratio of FIM 33,000 ($6200). According to sensitivity analysis the C/E-ratios were robust for all variables tested. Screening of male siblings of AAA patients produces incremental life-years at low cost thus screening of male siblings is highly recommended.


Blood group antigen expression in developing pancreas and in induced pancreatic cancer cells in Syrian hamsters.
Expression of blood group-related antigens and the binding pattern of Ulex europaeus-I (UEA-I) in fetal and newborn hamster pancreases was examined immunohistochemically by monoclonal antibodies (MoAbs) against blood group antigens and by peroxidase-conjugated UEA-I. The fetal hamster pancreas was detected histologically at the 12th day of gestation. MoAbs A, B and Le(a) were not immunoreactive with pancreatic cells in any stage of development nor were they after birth. Le(x) was first expressed in the luminal surface of duct cells at the 13th day of gestation, disappeared at the 15th day of gestation, was re-expressed after birth in acinar cells and was absent in the adult pancreas. Le(b) and Le(y) were expressed in acinar cells in late fetal and early newborn stages, but disappeared with maturation and were absent in the adult pancreas. UEA-I binding, however, was demonstrated in both fetal and adult pancreatic tissue. In cancer cells induced by BOP, blood group antigens except for Le(a) and UEA-I binding were found in various reactivity. These findings suggest that in hamsters (i) A and B antigens are tumor-related antigens; (ii) H, Le(b), Le(x) and Le(y) are oncofetal antigens; and (iii) fucosylation is an important event in cell differentiation.