Morphological and Dose-Dependent Study on the Effect of Methyl, Hexyl, and Dodecyl Rosmarinate on Staphylococcus carnosus LTH1502: Use of the Weibull Model.
The mechanisms of three antimicrobial rosmarinates (methyl-RE1, hexyl-RE6, and dodecyl-RE12) were investigated against Staphylococcus carnosus LTH1502. Scanning electron microscopy was used to determine the morphology of treated cells to gain information on potential changes in the site of action of compounds. The survival data obtained from antimicrobial activity assays were fitted to a nonlinear Weibull model to assess changes in inactivation behavior. Generally, esters became more effective with increasing length of the alkyl chain, resulting in a lower concentration for inhibition and inactivation. Weibull distribution parameters showed a downward concave inactivation pattern for RE1 above a critical concentration, indicative of a delayed log phase of the antimicrobial activity, with few cells being inactivated immediately after treatment and more cells being affected at later times. In contrast, esters having longer alkyl chains (RE6 and RE12) had an upward concave inactivation behavior, with more cells being inactivated immediately after addition of compounds. Cellular morphologies suggest that the antimicrobial mode of action of esters transitions from one that acts intracellularly (RE1) to one that predominately affects bacterial membrane (RE6 and RE12) due to changes in physicochemical properties of esters. Assessment that is based on the parameters of the Weibull model could, thus, be used to evaluate antimicrobial efficiency, in addition to MIC.


Treatment with etamsylate reduces haemolactia in lactating dairy cows.
This Research Communication describes the efficacy of etamsylate to reduce haemolactia in dairy cows. A dairy cow with haemolactia produces milk that is reddish or pinkish due to the presence of blood. Haemolactia causes economic loss because bloody milk is rejected by the industry and the consumers. A total of 58 dairy cows with haemolactia were included in the study and randomly divided into treated (n = 31) and control (n = 27) groups. Treatment consisted of three consecutive daily doses of etamsylate at 15 mg/kg, delivered intramuscularly. Milk production was recorded daily for 7 d, whether or not blood was detected in milk. The mean number of days with the presence of blood in milk in the treatment group was significantly lower (3·4 d) than in the control group (4·9 d). Treatment with etamsylate did not significantly affect milk yield. In conclusion, treatment with etamsylate reduces the number of days blood is observed in milk and it does not have any negative effect on milk production.


Stress mediates the relationship between sexual orientation and behavioral risk disparities.
Growing evidence documents elevated behavioral risk among sexual-minorities, including gay, lesbian, and bisexual individuals; however, tests of biological or psychological indicators of stress as explanations for these disparities have not been conducted. Data were from the 2005-2010 National Health and Nutrition Examination Survey, and included 9662 participants; 9254 heterosexuals, 153 gays/lesbians and 255 bisexuals. Associations between sexual orientation and tobacco, alcohol, substance, and marijuana use, and body mass index, were tested using the chi-square test. Stress, operationalized as depressive symptoms and elevated C-reactive protein, was tested as mediating the association between sexual orientation and behavioral health risks. Multiple logistic regression was used to test for mediation effects, and the Sobel test was used to evaluate the statistical significance of the meditating effect. Gays/lesbians and bisexuals were more likely to report current smoking (p < .001), a lifetime history of substance use (p < .001), a lifetime history of marijuana use (p < .001), and a lifetime period of risky drinking (p = .0061). The largest disparities were observed among bisexuals. Depressive symptoms partially mediated the association between sexual orientation and current smoking (aOR 2.04, 95% CI 1.59, 2.63), lifetime history of substance use (aOR 3.30 95% CI 2.20, 4.96), and lifetime history of marijuana use (aOR 2.90, 95% CI 2.02, 4.16), among bisexuals only. C-reactive protein did not mediate the sexual orientation/behavior relationship. Higher prevalence of current smoking and lifetime history of substance use was observed among sexual minorities compared to heterosexuals. Among bisexuals, depressive symptoms accounted for only 0.9-3% of the reduction in the association between sexual orientation and marijuana use and tobacco use, respectively. More comprehensive assessments of stress are needed to inform explanations of the disparities in behavioral risk observed among sexual minorities.


Nicotinergic Modulation of Attention-Related Neural Activity Differentiates Polymorphisms of DRD2 and CHRNA4 Receptor Genes.
Cognitive and neuronal effects of nicotine show high interindividual variability. Recent findings indicate that genetic variations that affect the cholinergic and dopaminergic neurotransmitter system impact performance in cognitive tasks and effects of nicotine. The current pharmacogenetic functional magnetic resonance imaging (fMRI) study aimed to investigate epistasis effects of CHRNA4/DRD2 variations on behavioural and neural correlates of visuospatial attention after nicotine challenge using a data driven partial least squares discriminant analysis (PLS-DA) approach. Fifty young healthy non-smokers were genotyped for CHRNA4 (rs1044396) and DRD2 (rs6277). They received either 7 mg transdermal nicotine or a matched placebo in a double blind within subject design prior to performing a cued target detection task with valid and invalid trials. On behavioural level, the strongest benefits of nicotine in invalid trials were observed in participants carrying both, the DRD2 T- and CHRNA4 C+ variant. Neurally, we were able to demonstrate that different DRD2/CHRNA4 groups can be decoded from the pattern of brain activity in invalid trials under nicotine. Neural substrates of interindividual variability were found in a network of attention-related brain regions comprising the pulvinar, the striatum, the middle and superior frontal gyri, the insula, the left precuneus, and the right middle temporal gyrus. Our findings suggest that polymorphisms in the CHRNA4 and DRD2 genes are a relevant source of individual variability in pharmacological studies with nicotine.


MAPK interacts with occludin and mediates EGF-induced prevention of tight junction disruption by hydrogen peroxide.
The MAPK (mitogen-activated protein kinase) pathway is a major intracellular signalling pathway involved in EGF (epithelial growth factor) receptor-mediated cell growth and differentiation. A novel function of MAPK activity in the mechanism of EGF-mediated protection of TJs (tight junctions) from H2O2 was examined in Caco-2 cell monolayers. EGF-mediated prevention of H2O2-induced increase in paracellular permeability was associated with the prevention of H2O2-induced Tyr-phosphorylation, Thr-dephosphorylation and cellular redistribution of occludin and ZO-1 (zonula occludin-1). EGF also prevented H2O2-induced disruption of the actin cytoskeleton and the dissociation of occludin and ZO-1 from the actin-rich detergent-insoluble fractions. MEK (MAPK/ERK kinase, where ERK stands for extracellular signal related kinase) inhibitors, PD98059 and U0126, completely blocked these protective effects of EGF on TJs. EGF rapidly increased the levels of phosphorylated MEK (p-MEK) in detergent-soluble fractions and phosphorylated ERK (p-ERK) in detergent-insoluble fractions. p-ERK was colocalized and co-immunoprecipitated with occludin. GST (glutathione S-transferase) pull-down assay showed that the C-terminal tail of occludin binds to p-ERK in Caco-2 cell extracts. Pair-wise binding studies using recombinant proteins demonstrated that ERK1 directly interacts with the C-terminal tail of occludin. Therefore the present study shows that ERK interacts with the C-terminal region of occludin and mediates the prevention of H2O2-induced disruption of TJs by EGF.


Possibility of cytoplasmic pre-tRNA splicing: the yeast tRNA splicing endonuclease mainly localizes on the mitochondria.
Pre-tRNA splicing has been believed to occur in the nucleus. In yeast, the tRNA splicing endonuclease that cleaves the exon-intron junctions of pre-tRNAs consists of Sen54p, Sen2p, Sen34p, and Sen15p and was thought to be an integral membrane protein of the inner nuclear envelope. Here we show that the majority of Sen2p, Sen54p, and the endonuclease activity are not localized in the nucleus, but on the mitochondrial surface. The endonuclease is peripherally associated with the cytosolic surface of the outer mitochondrial membrane. A Sen54p derivative artificially fixed on the mitochondria as an integral membrane protein can functionally replace the authentic Sen54p, whereas mutant proteins defective in mitochondrial localization are not fully active. sen2 mutant cells accumulate unspliced pre-tRNAs in the cytosol under the restrictive conditions, and this export of the pre-tRNAs partly depends on Los1p, yeast exportin-t. It is difficult to explain these results from the view of tRNA splicing in the nucleus. We rather propose a new possibility that tRNA splicing occurs on the mitochondrial surface in yeast.


Histopathology and the detection of avian bornavirus in the nervous system of birds diagnosed with proventricular dilatation disease.
Avian bornavirus (ABV) is currently considered a probable etiologic agent of proventricular dilatation disease (PDD) of psittacines. We tested 24 stored avian brain samples, processed for histopathology and retained following their submission for necropsy or histopathology to the Schubot Exotic Bird Center diagnostic laboratory in 1992. Thirteen of these samples were from birds diagnosed at that time as suffering from PDD. The remaining 11 samples were diagnosed as suffering from diseases other than PDD. Immunohistochemistry was performed using an antiserum directed against the ABV nucleoprotein (N-protein). Stained slides were read by an investigator unaware of their prior histopathology results. Cells containing ABV N-protein were present in the nervous tissues of all 13 PDD cases. One bird not previously diagnosed with PDD also had ABV N-protein in its brain. A review of this bird's necropsy report indicated that it was, most probably, also suffering from PDD. The remaining 10 non-PDD birds had no detectable N-protein in their brains. The N-protein was present in the cerebrum, cerebellum and spinal cord. These findings support other studies that indicate that ABV is an etiological agent of PDD.


Regulation of apoptosis and replicative senescence in CD8+ T cells from patients with viral infections.
Activated T lymphocytes are generated during an immune response. The induction of T lymphocyte proliferation is one way in which cell numbers can be controlled. However, once generated, the increased numbers of cells must be removed in order to re-establish cellular homoeostasis within the immune system. In this paper we describe how the numbers of activated T cells can be regulated by two distinct mechanisms, namely apoptosis and replicative senescence. In addition, we suggest that the regulation of cell clearance, as opposed to cell persistence, after an immune response is intimately involved in the generation of immune memory.


Lysergic acid diethylamide (LSD) and lisuride: differentiation of their neuropharmacological actions.
The nonhallucinogenic ergot derivative lisuride exerts many pharmacological effects that are similar to those of its hallucinogenic congener, lysergic acid diethylamide (LSD). Animals trained to discriminate between the presence of one drug and the other can be used to differentiate the actions of these compounds on a neuronal level. The discriminative stimulus effect of LSD (the LSD cue) is similar to that of the serotonin agonist quipazine, whereas the lisuride cue is similar to that of the dopamine agonist apomorphine. These data support the hypothesis that serotonin is intricately involved in the hallucinogenic effects of LSD.


Ras-Mediated Signal Transduction and Virulence in Human Pathogenic Fungi.
Signal transduction pathways regulating growth and stress responses are areas of significant study in the effort to delineate pathogenic mechanisms of fungi. In-depth knowledge of signal transduction events deepens our understanding of how a fungal pathogen is able to sense changes in the environment and respond accordingly by modulation of gene expression and re-organization of cellular activities to optimize fitness. Members of the Ras protein family are important regulators of growth and differentiation in eukaryotic organisms, and have been the focus of numerous studies exploring fungal pathogenesis. Here, the current data regarding Ras signal transduction are reviewed for three major pathogenic fungi: Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. Particular emphasis is placed on Ras-protein interactions during control of morphogenesis, stress response and virulence.


TRAIL death receptors as tumor suppressors and drug targets.
Various ways of targeting TRAIL-death receptors for the treatment of a diverse set of malignancies are being explored in ongoing clinical trials. Recent data of ours and others suggest that loss of the only death signaling receptor in mice (TRAIL-R) is associated with susceptibility to various stages of lymphomagenesis and carcinogenesis, perhaps in a complex cell- and model-specific manner. Myc-overexpressing B cell lymphomas with an intact TRAIL-R locus displayed a number of gene expression changes indicating resistance to TRAIL-R signaling. Herein we show some data on the use of recombinant human TRAIL (rhTRAIL) and gamma-radiation (10 Gy) in combination in an autochthonous mouse model for hepatocellular carcinoma. As cell death signaling through the death receptors is evolutionary conserved from zebra fish to man, novel genetically engineered mouse tumor models may prove useful in establishing in vivo models that excel our fundamental understanding of resistance to TRAIL-death receptor signaling, off-target effects from TRAIL-death receptor targeting compounds and help in identifying a clinically cogent rationale for efficient targeting of TRAIL death receptors in patients. Once established, mouse tumor models may prove to be a useful tool in understanding TRAIL-death receptor signaling.


Minimal contact treatment for smoking cessation. A placebo controlled trial of nicotine polacrilex and self-directed relapse prevention: initial results of the Stanford Stop Smoking Project.
To determine the effectiveness of nicotine polacrilex combined with self-administered relapse prevention materials in maintaining smoking cessation, we conducted a randomized, double-blind, placebo controlled trial. Volunteers aged 18 to 65 years responding to media announcements were required to quit smoking for 48 hours without assistance. Of 1844 potential participants, 136 were medically excluded, 535 declined to make a quit attempt, and 573 were unable to quit, leaving 600 participants (35%) who were randomized. Eight self-help relapse prevention modules were mailed weekly. Gum was used either ad lib for smoking urges or on a fixed, hourly schedule (12 pieces per day). Only 15% of the subjects in each gum group stopped using the gum altogether because of side effects, but only 20% of the ad lib groups and 40% of the fixed-dosage group used at least eight pieces of gum per day during the first week. The abstinence rates (for at least seven days) at the six-month follow-up were 31% in both active gum groups and 22% in the placebo and no gum groups. Relapse rates in the two active gum groups were about half those in the placebo and no gum groups. Nicotine polacrilex may be a useful adjunct to minimal contact smoking cessation formats, which have broad appeal. Also, minimal contact relapse prevention programs may assist physicians in helping patients to maintain smoking cessation using nicotine polacrilex.


Comprehensive analysis of antibody responses to streptococcal and tissue antigens in patients with acute rheumatic fever.
Acute rheumatic fever (ARF) is an autoimmune disease occurring in individuals following untreated group A streptococcal infection believed to be triggered by antibodies to bacterial components that cross-react with human tissues. We developed a multiplexed immunoassay for the simultaneous quantitation of antibodies to nine streptococcal-related antigens including streptolysin O (SLO), DNase B, collagen I and IV, fibronectin, myosin, group A carbohydrate, M6 protein and streptococcal C5a peptidase. Utilizing this method, we examined serum from 49 ARF, 58 pharyngitis patients and age- and sex-matched controls in samples collected at initial disease onset, and at 4 weeks, 6 months and 1 year after diagnosis. Antibody responses were significantly higher for SLO, DNase B, M6 protein, group A carbohydrate and the cross-reactive antigens collagen I and myosin in ARF compared with pharyngitis patients (P <or= 0.05). Moreover, we found significantly elevated antibody responses in the ARF patients with rheumatic heart disease to fibronectin and collagen I compared with ARF patients without heart disease. The major differences between the ARF patients with and without carditis appear to be in the immune response to the putative heart valve components, collagen I and fibronectin.


Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit.
Background: 4-(n-Octyloxy)aniline is a known component in the elaboration of organic materials with mesogenic properties such as N-substituted Schiff bases, perylene bisimide assemblies with a number of 2-amino-4,6-bis[4-(n-octyloxy)phenylamino]-s-triazines, amphiphilic azobenzene-containing linear-dendritic block copolymers and G-0 monomeric or dimeric dendritic liquid crystals with photochromic azobenzene mesogens. The present ab initio study explores a previously unknown use of 4-(n-octyloxy)aniline in the synthesis, structure and supramolecular behaviour of new dendritic melamines. Results: Starting from 4-(n-octyloxy)aniline, seven G-2 melamine-based dendrimers were obtained in 29-79% overall yields. Their iterative convergent- and chemoselective synthesis consisted of SN2-Ar aminations of cyanuric chloride and final triple N-acylations and Williamson etherifications (→ G-2 covalent trimers) or stoichiometric carboxyl/amino 1:3 neutralisations (→ G-2 ionic trimers). These transformations connected G-1 chloro- and amino-termini dendrons to m-trivalent cores (triazin-2,4,6-triyl and benzene-1,3,5-triyl units) or tripodands (central building blocks), such as N-substituted melamines with 4-hydroxyphenyl or phenyl-4-oxyalkanoic motifs. Owing to the diversity of cores and central building blocks, the structural assortment of the dendritic series was disclosed by solvation effects (affecting reactivity), rotational stereodynamism and self-organisation phenomena (determining a vaulted and/or propeller macromolecular shape in solution). DFT calculations (in solution), (VT) NMR and IR (KBr) spectroscopy supported these assignments. TEM analysis revealed the ability of the title compounds towards self-assembling into homogeneously packed spherical nano-aggregates. Conclusions: The (non)covalent synthesis and step-by-step structural elucidation of novel G-2 melamine dendrimers based on 4-(n-octyloxy)aniline are reported. Our study demonstrates the crucial influence of the nature (covalent vs ionic) of the dendritic construction in tandem with that of its central building blocks on the aptitude of dendrimers to self-organise in solution and to self-assembly in the solid state.


Gaze and visual search strategies of children with Asperger syndrome/high functioning autism viewing a magic trick.
To examine visual search patterns and strategies used by children with and without Asperger syndrome/high functioning autism (AS/HFA) while watching a magic trick. Limited responsivity to gaze cues is hypothesised to contribute to social deficits in children with AS/HFA. Twenty-one children with AS/HFA and 31 matched peers viewed a video of a gaze-cued magic trick twice. Between the viewings, they were informed about how the trick was performed. Participants' eye movements were recorded using a head-mounted eye-tracker. Children with AS/HFA looked less frequently and had shorter fixation on the magician's direct and averted gazes during both viewings and more frequently at not gaze-cued objects and on areas outside the magician's face. After being informed of how the trick was conducted, both groups made fewer fixations on gaze-cued objects and direct gaze. Information may enhance effective visual strategies in children with and without AS/HFA.


Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells.
The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate (ATP) by supporting cells in the Kölliker's organ. However, the mechanisms responsible for initiating spontaneous ATP release have not been determined. Our previous study revealed that telomerase reverse transcriptase (TERT) is expressed in the basilar membrane during the first postnatal week. Its role in cochlear development remains unclear. In this study, we investigated the expression and role of TERT in postnatal cochlea supporting cells. Our results revealed that in postnatal cochlear Kölliker's organ supporting cells, TERT shifts from the nucleus into the cytoplasm over time. We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo. Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis, suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions. We observed increased ATP synthesis, release and activation of purine signaling systems in supporting cells during the first 10 postnatal days. The phenomenon that TERT translocation coincided with changes in ATP synthesis, release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system. Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.


A new immunodeficient hyperglycaemic mouse model based on the Ins2Akita mutation for analyses of human islet and beta stem and progenitor cell function.
To develop and validate a new immunodeficient mouse strain that spontaneously develops a non-autoimmune hyperglycaemia to serve as a diabetic host for human islets and human beta stem and progenitor cells without the need for induction of hyperglycaemia by toxic chemicals with their associated side effects. We generated and characterised a new strain of immunodeficient spontaneously hyperglycaemic mice, the NOD-Rag1null Prf1null Ins2Akita strain and compared this strain with the NOD-scid Il2rgammanull (also known as Il2rg) immunodeficient strain rendered hyperglycaemic by administration of a single dose of streptozotocin. Hyperglycaemic mice were transplanted with human islets ranging from 1,000 to 4,000 islet equivalents (IEQ) and were monitored for normalisation of blood glucose levels. NOD-Rag1null Prf1null Ins2Akita mice developed spontaneous hyperglycaemia, similar to Ins2Akita-harbouring strains of immunocompetent mice. Histological examination of islets in the host pancreas validated the spontaneous loss of beta cell mass in the absence of mononuclear cell infiltration. Human islets transplanted into spontaneously diabetic NOD-Rag1null Prf1null Ins2Akita and chemically diabetic NOD-scid Il2rgammanull mice resulted in a return to euglycaemia that occurred with transplantation of similar beta cell masses. The NOD-Rag1null Prf1null Ins2Akita mouse is the first immunodeficient, spontaneously hyperglycaemic mouse strain described that is based on the Ins2Akita mutation. This strain is suitable as hosts for human islet and human beta stem and progenitor cell transplantation in the absence of the need for pharmacological induction of diabetes. This strain of mice also has low levels of innate immunity and can be engrafted with a human immune system for the study of human islet allograft rejection.


Bromocriptine for levodopa-induced motor complications in Parkinson's disease.
To assess the efficacy and safety of adjunct bromocriptine (BR) therapy compared to placebo in the treatment of Parkinson's disease (PD) patients with motor complications. Sources including the Cochrane Library, a MEDLINE search-strategy, reference lists of the reviews found by the MEDLINE search-strategy, Sandoz (producer of BR), symposia reports, PD handbooks, SCISEARCH, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomized controlled trials (RCTs) of interest. Randomized trials were eligible for inclusion if they evaluated the efficacy of BR as adjunctive to LD-therapy compared to placebo in PD patients with motor complications. Outcome measures that were evaluated, included occurrence and severity of motor complications, scores on impairment and disability, and the occurrence of side effects. Three reviewers independently reviewed the quality of identified trials. To determine the feasibility of a quantitative systematic review each eligible study was evaluated concerning the methodological quality. This review identified important shortcomings regarding the methodological quality of eight trials. All studies failed to describe adequately their randomization procedure. Consultation with the trialists revealed that three trials adequately randomized their patients. Contrary to the information of the published report, one placebo-controlled trial appeared to be carried out as an open study and was therefore excluded. The remaining seven trials were reported to be carried out according to a double-blind design, although one was unblinded after five weeks. There was a conspicuous variability in the duration of trials: four to forty weeks (mean 14 weeks). None of the included trials was performed according to the intention-to-treat principle. With regard to the inclusion criteria, it frequently remained unclear if PD patients actually suffered from motor complications. Prominent differences between studies regarding the baseline characteristics and the rate by which BR was introduced during the titration phase were found. Major differences between studies emerged concerning the applied outcomes. The various methods used to evaluate the occurrence and/or severity of motor complications lacked a sound clinimetric basis. A great diversity of scales to evaluate impairment and disability was applied. None of the included trials reported whether scores on impairment and disability level referred to the "on"- or "off"-phase. This review highlights major methodological problems and sources of heterogeneity that not only hamper the comparability of trials but also preclude a conclusion on the efficacy of BR in the adjunct treatment of PD patients with motor complications.


Collaboration: an innovative education/business partnership.
Healthy People 2010 initiatives encourage the collaborative partnership goals described in this article. The partnership developed between a UB School of Nursing faculty member, her students, and several case managers at Health-Now Now has been a richly rewarding experience. The opportunities afforded by this partnership have expanded experiences for faculty, students, and case managers in a managed care environment. This partnership has enabled participants to initiate practical, cost-effective methods for improving community-based services. These partnerships should yield significant changes in health behaviors and health outcomes among the American public. Valanis states it most succinctly: "The nurse of the 21st century must innovate, coordinate, and monitor services for populations within the health care system in which she works and interacts with crucial services outside the system. Her or his patient is not only an individual or even the family but the entire community."


Separation of intramembrane charging components in low-calcium solutions in frog skeletal muscle.
The inactivation of charge movement components by small (-100 to -70 mV) shifts in holding potential was examined in voltage-clamped intact amphibian muscle fibers in low [Ca2+], Mg(2+)-containing solutions. The pulse protocols used both large voltage excursions and smaller potential steps that elicited prolonged (q gamma) transients. Charge species were distinguished through the pharmacological effects of tetracaine. These procedures confirmed earlier observations in cut fibers and identified the following new properties of the q gamma charge. First, q gamma, previously defined as the tetracaine-sensitive charge, is also the component primarily responsible for the voltage-dependent inactivation induced by conditions of low extracellular [Ca2+]. Second, this inactivation separates a transient that includes a "hump" component and which has kinetics and a voltage dependence distinct from the monotonic decay that remains. Third, q gamma, previously associated with delayed charge movements, can also contribute significant charge transfer at early times. These findings suggest that the parallel inhibition of calcium signals and charge movements reported in low [Ca2+] solutions arises from influences on q gamma charge (Brum et al., 1988a, b). They also reconcile reports that implicate tetracaine-sensitive (q gamma) charge in excitation-contraction coupling with evidence that early intramembrane events are also involved in this process (Pizarro et al., 1989). Finally, they are relevant to hypotheses of possible feedback or feed-forward roles of q gamma in excitation-contraction coupling.


Waveguide-coupled nanowire as an optical antenna.
We study the optical coupling between a gold nanowire and a silver ion-exchanged waveguide, with special emphasis on the nanowire antenna radiation pattern. We measure the radiation patterns of waveguide-coupled gold nanowires with a height of 70 nm and width of 50 or 150 nm in the 450-700 nm spectral range for TE and TM polarizations. We perform a systematic theoretical study on the wavelength, polarization, nanowire size, and material dependences on the properties of the radiation pattern. We also give some elements concerning absorption and near-field. Experiments and calculations show localized plasmon resonance for the polarization orthogonal to the wire (far-field resonance at 580 nm for the smallest wire and 670 nm for the widest). It is shown that a great variety of radiation patterns can be obtained, together with a high sensitivity to a change of one parameter, particularly near-resonance.


Designed Spider Silk-Based Drug Carrier for Redox- or pH-Triggered Drug Release.
Targeted drug delivery and controlled drug release can be obtained using specifically designed polymers as carriers. Due to their biocompatibility and biodegradability and especially the lack of an immune response, materials made of spider silk proteins are promising candidates for use in such applications. Particles made of recombinant spider silk proteins have previously been shown to be suitable drug and gene carriers as they could readily be loaded with various drug substances or biologicals, and subsequent release was observed over a defined period of time. However, the respective substances were bound non-covalently via hydrophobic or charge-charge interactions, and hence, the release of loaded substances could not be spatio-temporally controlled. Here, we present a setup of chemically modified recombinant spider silk protein eADF4 and variants thereof, combining their well-established biocompatible properties with covalent drug binding and triggered release upon changes in the pH or redox state, respectively. The usefulness of the spider silk platform technology was shown with model substances and cytostatic drugs bound to spider silk particles or films via a pH-labile hydrazine linker as one option, and the drugs could be released from the spider silk carriers upon acidification of the environment as seen, e.g., in tumorous tissues or endo/lysosomes. Sulfhydryl-bearing spider silk variants allowed model substance release if exposed to intracellular GSH (glutathione) levels as a second coupling option. The combination of non-immunogenic, nontoxic spider silk materials as drug carriers with precisely triggerable release chemistry presents a platform technology for a wide range of applications.


Structural robustness of mammalian transcription factor networks reveals plasticity across development.
Network biology aims to understand cell behavior through the analysis of underlying complex biomolecular networks. Inference of condition-specific interaction networks from epigenomic data enables the characterization of the structural plasticity that regulatory networks can acquire in different tissues of the same organism. From this perspective, uncovering specific patterns of variation by comparing network structure among tissues could provide insights into systems-level mechanisms underlying cell behavior. Following this idea, here we propose an empirical framework to analyze mammalian tissue-specific networks, focusing on characterizing and contrasting their structure and behavior in response to perturbations. We structurally represent the state of the cell/tissue by condition specific transcription factor networks generated using DNase-seq chromatin accessibility data, and we profile their systems behavior in terms of the structural robustness against random and directed perturbations. Using this framework, we unveil the structural heterogeneity existing among tissues at different levels of differentiation. We uncover a novel and conserved systems property of regulatory networks underlying embryonic stem cells (ESCs): in contrast to terminally differentiated tissues, the promiscuous regulatory connectivity of ESCs produces a globally homogeneous network resulting in increased structural robustness. We show that this property is associated with a more permissive, less restrictive chromatin accesibility state in ESCs. Possible biological consequences of this property are discussed.


Prognostic Value of the Pattern of Non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) Bleeding Risk Score for Long-Term Mortality After Percutaneous Coronary Intervention.
The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score has been proposed to predict the risk of bleeding events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS bleeding risk score for long term all-cause mortality, cardiac mortality and hospitalization due to heart failure has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS bleeding risk score for all-cause and cardiac mortalities and hospitalization due to heart failure after PCI. Consecutive 1061 patients who had undergone PCI were divided into 3 groups based on the PARIS bleeding risk score; low (n = 112), intermediate (n = 419) and high-risk groups (n = 530). We prospectively followed up the 3 groups for all-cause and cardiac mortalities and hospitalization due to heart failure. Kaplan-Meier analysis revealed that all of the outcomes were highest in the high-risk group among the 3 groups (P < 0.001, P < 0.001 and P < 0.001 respectively). Multivariable Cox proportional hazard analysis, adjusted for confounding factors, revealed that all-cause mortality of the intermediate or high-risk groups was higher than those of the low-risk group (adjusted hazard ratio 6.06 and 12.50, P = 0.013 and P < 0.001, respectively). The PARIS bleeding risk score is a significant indicator of prognosis for all-cause mortality in patients after PCI.


Natural resistance of rose petals to microbial attack.
Petals of red, yellow and white roses (Rosa damascene Mill.) of the family Rosaceae were extracted with (1:1) methylene chloride/methanol and tested for their antimicrobial activities against four species of Gram-positive bacteria (Bacillus cereus, Bacillus subtilis, Micrococcus luteus and Staphylococcus aureus), five species of Gram-negative bacteria (Enterobacter aerogenes, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Serratia marcescens) and five species of fungi (Penicillium notatum, Aspergillus niger, Rhizopus stolonifer, Saccharomyces cerevisiae and Fusarium oxysporum). All of the crude extracts showed a wide range of antimicrobial activities according to the tested organism and rose's type. Micrococcus luteus was found to be the most susceptible bacteria to all crude extracts. Red and yellow petal extracts showed much higher antibacterial activity than the white petals extract. Bacillus subtilis was found to be the least susceptible to all extracts. The fungus, Penicillium notatum was found to be the most susceptible with white petal extract being the most effective. Saccharomyces cerevisiae and Fusarium oxysporum were the least susceptible to all extracts. White roses extract showed much higher antifungal activities against Penicillium notatum than red or yellow roses, therefore, it was subjected to several bioassay guided chromatographic fractionations and purification to isolate the active chemical(s) responsible for the antifungal activity. Chemical structure of the isolated antifungal compounds were identified by spectroscopy techniques and found to be a γ-sitosterol and (Z,Z)-9,12-octadecadienoic acid. Antibacterial activity of the various types of rose extracts were due to complex mixtures of organic compounds which are still under chemical investigation and will be published later.


Developing and Testing Electronic Health Record-Derived Caries Indices.
Caries indices, the basis of epidemiologic caries measures, are not easily obtained in clinical settings. This study's objective was to design, test, and validate an automated program (Valid Electronic Health Record Dental Caries Indices Calculator Tool [VERDICT]) to calculate caries indices from an electronic health record (EHR). Synthetic use case scenarios and actual patient cases of primary, mixed, and permanent dentition, including decayed, missing, and filled teeth (DMFT/dmft) and tooth surfaces (DMFS/dmfs) were entered into the EHR. VERDICT measures were compared to a previously validated clinical electronic data capture (EDC) system and statistical program to calculate caries indices. Four university clinician-researchers abstracted EHR caries exam data for 45 synthetic use cases into the EDC and post-processed with SAS software creating a gold standard to compare the -VERDICT-derived caries indices. Then, 2 senior researchers abstracted EHR caries exam data and calculated caries indices for 24 patients, allowing further comparisons to VERDICT indices. Agreement statistics were computed among abstractors, and discrepancies were resolved by consensus. Agreement statistics between the 2 final-phase abstractors and the VERDICT measures showed extremely high concordance: Lin's concordance coefficients (LCCs) >0.99 for dmfs, dmft, DS, ds, DT, dt, ms, mt, FS, fs, FT, and ft; LCCs >0.95 for DMFS and DMFT; and LCCs of 0.92-0.93 for MS and MT. Caries indices, essential to developing primary health outcome measures for research, can be reliably derived from an EHR using VERDICT. Using these indices will enable population oral health management approaches and inform quality improvement efforts.


Reconstruction of the heel pad by muscle transposition and split skin graft.
Reconstruction of the pad of the heel by transposition of the flexor digitorum brevis muscle and split skin graft has proved to be quite durable, padding of the heel is adequate and protective pressure sensation has returned to the area. This procedure offers a simple one stage alternative to the cross-leg or local skin flaps for management of this difficult problem.


Tracheal leiomyosarcoma: a unique cause of stridor.
A 26-year-old man presented with a 2-week history of hemoptysis and progressive upper airway obstruction. Roentgenograms and bronchoscopy confirmed a tracheal tumor, and a primary leiomyosarcoma was resected.


[Frontotemporal dementia].
Frontotemporal dementia (FTD), although less common than Alzheimer's, constitutes a significant percentage of the degenerative dementias, making up 8 to 17% of patients who die with dementia before the age of 70. Several clinical presentations have been described for many authors, which are included in classical behaviour disorder of frontal lobe dementia and in language alterations of progressive aphasias. Classification and diagnosis criteria's of FTP are sometime controversial in literature. So, the authors give an overview of principal's aspects in this area, with focus on clinical, imagiological, patghological and genetic perspective. Furthermore, taken in account this revision was also made a characterization of the patients followed in Dementia Outpatient Clinical Care of our hospital. In these patient characteristics review the follow parameters were analysed: FDT clinical diagnosis; demographics, clinical, imagiological, neuropsychological aspects; and disease evolution. An retrospective study that allowed correlation between some aspects, namely clinical presentation with imagiological and neuropsychological findings. With this revision work, the authors pretend to alert for the relevance of FTD diagnosis, probably misdiagnosticated.


Serum insulin-like growth factor-I, insulin-like growth factor binding proteins, and bone mineral content in hyperthyroidism.
The mechanism by which thyroid hormones promote bone growth has not yet been elucidated. In vitro, thyroid hormones stimulate insulin-like growth factor-I (IGF-I) production by osteoblasts, which is important for the anabolic effects of the hormone on bone. To determine whether the IGF-I/IGF binding protein (IGFBP) profile is affected when thyroid hormone production is altered in vivo, we studied 36 women who had recently been diagnosed with hyperthyroidism (age: 29-67 years; 19 with Graves' disease, 17 with toxic nodular goiter) and 36 age-matched healthy women as controls. Serum IGF-I, and its binding proteins (IGFBP-3, IGFBP-4, and IGFBP-5), as well as bone mineral density (BMD) at the lumbar spine, femoral neck, and radius midshaft were measured before and 1 year after antithyroid (methimazole) treatment. Serum IGF-I levels were significantly increased in the hyperthyroid patients before treatment (214 +/- 18.2 ng/mL vs. 145 +/- 21.3 ng/mL; p < 0.05). There was no difference in IGF-I levels of patients with Graves' disease and toxic nodular goiter. Serum IGF-I concentrations returned to normal after treatment with methimazole. Serum IGFBP-3 and IGFBP-4 values were significantly elevated in the hyperthyroid group before treatment (3960 +/- 220 ng/mL and 749.7 +/- 53.1 ng/mL vs. 2701 +/- 180 ng/mL and 489.9 +/- 32.4 ng/mL; p < 0.05 and p < 0.01, respectively) and were reduced to those of controls after treatment. Serum IGFBP-5 of hyperthyroid subjects was not different from that of controls either before or after therapy. Serum free thyroxine showed a positive correlation with serum levels of IGF-I (r = 0.73, p < 0.05), IGFBP-3 (r = 0.59, p < 0.05), and IGFBP-4 (r = 0.67, p < 0.05) but not IGFBP-5. BMD at the radius midshaft was significantly lower in hyperthyroid patients at the start of the study and showed a positive correlation with serum IGF-I (r = 0.58; p < 0.001) and a negative correlation with IGFBP-4 (r = -0.61; p < 0.05). Radius BMD showed a 7.2% increase in the hyperthyroid group after 1 year of methimazole treatment, and the correlation between BMD and serum IGF-I disappeared. Our data indicate that thyroid hormones may influence the IGF-I/IGFBP system in vivo in hyperthyroidism. The anabolic effects of increased levels of IGF-I may be limited in hyperthyroidism due to the increases of inhibitory IGFBPs that can counteract the anabolic effects and contribute to the observed net bone loss.


Ideal role behaviours as seen by dentists and patients themselves and by their role partners: do they differ?
The aim of this study was to determine whether patients and dentists differ in their ideal role expectations concerning each others behaviour. This was done by further analysing a set of data containing responses to 124 five-class Likertian statements about ideal role expectations and questions about the background of the respondents with regard to different aspects of the dentist-patient relationship. The study groups consisted of a representative sample of lay people and all dentists in the Finnish Provinces Kuopio and North Karelia. To extract areas of ideal role expectations for both dentists and patients, orthogonal factor analyses were applied to the data. To evaluate the dissimilarity of the structure of the factor analyses, rotated factor matrices were used to conduct transformation analysis. Similarities between the ideal role expectations of dentists and patients were studied. When studied with transformation analysis, the ideal role expectations of dentists and patients were found to differ for both the ideal patient and the ideal dentist. However, dentists and patients shared expectations concerning one characteristic of the ideal dentist i.e. the importance of mutual communication, which was also considered the most important characteristic of the ideal dentist. For the characteristics of the ideal patient, the two groups shared the same expectations concerning the manageability of the patient. Previous research has compared dentist and patient expectations based only on single statements. No reports based on factor analysed data have been published, but transformation analysis was found to provide a useful tool for statistical evaluation of the dissimilarity of the factor structures.


Information loss recovery for block-based image coding techniques-a fuzzy logic approach.
A new technique to recover the information loss in a block-based image coding system is developed in this paper. The proposed scheme is based on fuzzy logic reasoning and can be divided into three main steps: (1) hierarchical compass interpolation/extrapolation (HCIE) in the spatial domain for initial recovery of lost blocks that mainly contain low-frequency information such as smooth background (2) coarse spectra interpretation by fuzzy logic reasoning for recovery of lost blocks that contain high-frequency information such as complex textures and fine features (3) sliding window iteration (SWI), which is performed in both spatial and spectral domains to efficiently integrate the results obtained in steps (1) and (2) such that the optimal result can be achieved in terms of surface continuity on block boundaries and a set of fuzzy inference rules. The proposed method, which is suitable for recovering both isolated and contiguous block losses, provides a new approach for error concealment of block-based image coding systems such as the JPEG coding standard and vector quantization-based coding algorithms. The principle of the proposed scheme can also be applied to block-based video compression schemes such as the H.261, MPEG, and HDTV standards. Simulation results are presented to illustrate the effectiveness of the proposed method.


A Comparative Study of 1D Descriptors Supported CoMFA and CoMSIA QSAR Models to Gain Novel Insights into 1,2,4-Triazoles Acting As Antitubercular Agents.
Tuberculosis is one of the leading causes of deaths due to infectious disease worldwide. There is an urgent need for developing new drugs due to the rising incidents of drug resistance. Previously, triazole molecules showing antitubercular activity, were reported. Various computational tools pave the way for a rational approach to understanding the structural importance of these compounds in inhibiting the growth of Mycobacterium Tuberculosis. The aim of this study is to develop and compare two different QSAR models based on a set of previously reported triazole molecules and use the best one for gaining structural insights into those molecules. In this current study, two separate models were made with CoMFA and CoMSIA descriptors based on a dataset of triazole molecules showing antitubercular activity. Several one dimensional (1D) descriptors were added to each of the models and the validation results and contour data generated from them were compared. The best model was analysed to give a detailed understanding of the triazole molecules and their role in the antitubercular activity. The r2, q2, predicted r2 and SEP (Standard error of prediction) for the CoMFA model were 0.866, 0.573, 0.119 and 0.736 respectively and for the CoMSIA model, the r2, q2, predicted r2 and SEP were calculated to be 0.998, 0.634, 0.013 and 0.869 respectively. Although both the QSAR models produced acceptable internal and external validation scores, but the CoMSIA results were significantly better. The CoMSIA contours also provided a better match than CoMFA with most of the features of the active compound 30b. Hence, the CoMSIA model was chosen and its contours were explored for gaining structural insights into the triazole molecules. The CoMSIA contours helped us understand the role of several atoms and groups of the triazole molecules in their biological activity. The possibilities for substitution in the triazole compounds that would enhance the activity were also analyzed. Thus, this study paves the way for designing new antitubercular drugs in future.


Cooperative and diminutive effects of pnicogen bonds and cation-π interactions.
The interplay between pnicogen bonds and cation-π interactions has been investigated at the MP2/aug-cc-pVDZ level. Interesting cooperative and diminutive effects are observed when pnicogen bonds and cation-π interactions coexist in the same complex. These effects have been analyzed in terms of the structural, energetic, and charge-transfer properties of the complexes. The variations in electron density at critical points of the intermolecular bond have been used to analyze bond strengthening or weakening. The nature of the interactions and the mechanisms of cooperative and diminutive effects have been studied by means of symmetry-adapted perturbation theory and molecular electrostatic potentials.


Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period.
To determine if there has been a statistically significant change in pregnancy loss and preterm delivery rates in patients with systemic lupus erythematosus (SLE). We analyzed the pregnancy outcomes of our SLE patients over the past 3 years and reviewed the literature over the past 40 years. We extracted pregnancy loss and preterm delivery data from reports of postdiagnosis SLE pregnancies. Studies were grouped into 5-year periods and weighted according to sample size. Group means, calculated for each study period, were plotted using linear regression to determine significance, and compared with population norms for the same periods. The rate of loss in SLE pregnancies over the past 40 years decreased from a mean of 43% in 1960-1965 to 17% in 2000-2003 (r2 = 0.648). This approximates the pregnancy loss rate in the general US population. Preterm deliveries were not uniformly reported and were rarely stratified into spontaneous or physician-initiated. Prior to 1980, it was not possible to derive group means for each time period. From 1980 to 2002, however, there was a trend toward a decrease in preterm births in SLE pregnancies, although they continue to be more frequent in SLE than in the general population. Improvements in disease management and perinatal monitoring have resulted in a significant decrease in pregnancy loss in SLE over the last 40 years and a trend toward decreased preterm deliveries over the last 20 years in comparison to the general population. These advances highlight the importance of collaboration between rheumatologists and perinatologists. Given these data, the description of SLE-associated pregnancy could be revised to reflect a more positive prognosis for mother and fetus.


Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis.
Lymphocyte extravasation from the high endothelial venules (HEVs) of lymph nodes is crucial for the maintenance of immune homeostasis, but its molecular mechanism remains largely unknown. In this article, we report that lymphocyte transmigration across the basal lamina of the HEVs is regulated, at least in part, by autotaxin (ATX) and its end-product, lysophosphatidic acid (LPA). ATX is an HEV-associated ectoenzyme that produces LPA from lysophosphatidylcholine (LPC), which is abundant in the systemic circulation. In agreement with selective expression of ATX in HEVs, LPA was constitutively and specifically detected on HEVs. In vivo, inhibition of ATX impaired the lymphocyte extravasation from HEVs, inducing lymphocyte accumulation within the endothelial cells (ECs) and sub-EC compartment; this impairment was abrogated by LPA. In vitro, both LPA and LPC induced a marked increase in the motility of HEV ECs; LPC's effect was abrogated by ATX inhibition, whereas LPA's effect was abrogated by ATX/LPA receptor inhibition. In an in vitro transmigration assay, ATX inhibition impaired the release of lymphocytes that had migrated underneath HEV ECs, and these defects were abrogated by LPA. This effect of LPA was dependent on myosin II activity in the HEV ECs. Collectively, these results strongly suggest that HEV-associated ATX generates LPA locally; LPA, in turn, acts on HEV ECs to increase their motility, promoting dynamic lymphocyte-HEV interactions and subsequent lymphocyte transmigration across the basal lamina of HEVs at steady state.


Psychological interventions for alcohol use disorders in people living with HIV/AIDS: a systematic review.
Alcohol use disorders (AUDs) in people living with HIV/AIDS (PLWH) are a significant impediment to achieving virological control. HIV non-suppression in PLWH with AUDs is mainly attributable to sub-optimal antiretroviral therapy adherence. Sub-optimal adherence makes control of the epidemic elusive, considering that effective antiretroviral treatment and viral suppression are the two key pillars in reducing new infections. Psychological interventions have been proposed as effective treatments for the management of AUDs in PLWH. Evidence for their effectiveness has been inconsistent, with two reviews (2010 and 2013) concluding a lack of effectiveness. However, a 2017 review that examined multiple HIV prevention and treatment outcomes suggested that behavioural interventions were effective in reducing alcohol use. Since then, several studies have been published necessitating a re-examination of this evidence. This review provides an updated synthesis of the effectiveness of psychological interventions for AUDs in PLWH. A search was conducted in the following databases: PubMed, Cochrane Central Register of Trials (CENTRAL), MEDLINE (Ovid), EMBASE, PsychInfo (Ovid) and Clinical trials.gov (clinicaltrials.gov) for eligible studies until August 2018 for psychotherapy and psychosocial interventions for PLWH with AUDs. Two reviewers independently screened titles, abstracts and full texts to select studies that met the inclusion criteria. Two reviewers independently performed data extraction with any differences resolved through discussion. Risk of bias was assessed by two independent reviewers using the Cochrane risk of bias tool, and the concordance between the first and second reviewers was 0.63 and between the first and third reviewers 0.71. Inclusion criteria were randomised controlled trials using psychological interventions in people aged 16 and above, with comparisons being usual care, enhanced usual care, other active treatments or waitlist controls. A total of 21 studies (6954 participants) were included in this review. Studies had diverse populations including men alone, men and women and men who had sex with men (MSM). Use of motivational interviewing alone or blended with cognitive behavioural therapy (CBT) and technology/computer-assisted platforms were common as individual-level interventions, while a few studies investigated group motivational interviewing or CBT. Alcohol use outcomes were all self-report and included assessment of the quantity and the frequency of alcohol use. Measured secondary outcomes included viral load, CD4 count or other self-reported outcomes. There was a lack of evidence for significant intervention effects in the included studies. Isolated effects of motivational interviewing, cognitive behavioural therapy and group therapy were noted. However for some of the studies that found significant effects, the effect sizes were small and not sustained over time. Owing to the variation in outcome measures employed across studies, no meta-analysis could be carried out. This systematic review did not reveal large or sustained intervention effects of psychological interventions for either primary alcohol use or secondary HIV-related outcomes. Due to the methodological heterogeneity, we were unable to undertake a meta-analysis. Effectiveness trials of psychological interventions for AUDs in PLWH that include disaggregation of data by level of alcohol consumption, gender and age are needed. There is a need to standardise alcohol use outcome measures across studies and include objective biomarkers that provide a more accurate measure of alcohol consumption and are relatively free from social desirability bias. PROSPERO CRD 42017063856 .


Injection of platelet- and leukocyte-rich plasma at the junction of the proximal sesamoid bone and the suspensory ligament branch for treatment of yearling Thoroughbreds with proximal sesamoid bone inflammation and associated suspensory ligament branch desmitis.
To determine the effects of treatment with platelet- and leukocyte-rich plasma (PRP) on future 2-, 3-, and 4-year-old racing performance of yearling Thoroughbreds with proximal sesamoid bone inflammation and associated suspensory ligament branch (SLB) desmitis. Randomized clinical trial. 39 yearling Thoroughbreds. Yearling Thoroughbreds with radiographic evidence of performance-limiting proximal sesamoid bone inflammation and ultrasonographic evidence of associated SLB desmitis were identified and randomly assigned to undergo PRP (treatment group) or saline (0.9% NaCl) solution (control group) injection at the affected SLB-proximal sesamoid bone junction. Race records of horses for the 2-, 3-, and 4-year-old racing years were obtained. Data regarding amount of money earned and number of races started were used as outcome measures, and results for groups were compared. Horses treated with PRP were significantly more likely to start at least 1 race during the 2-year-old racing year than were horses treated with saline solution; no significant differences were detected between groups regarding that variable for the 3- and 4-year-old racing years. No significant differences between groups were detected regarding earnings for any racing year. Although PRP-treated horses were more likely to start a race during the 2-year-old racing year versus control group horses, results for horses in each group were not significantly different for the 3- and 4-year-old racing years. Therefore, the PRP treatment protocol evaluated in this study did not seem to improve future racing performance of yearling Thoroughbreds with proximal sesamoid bone inflammation and associated SLB desmitis, compared with injection of saline solution.


The evolutionary ecology of dwarfism in three-spined sticklebacks.
1. Body size is a defining phenotypic trait, but the ecological causes of its evolution are poorly understood. Most studies have considered only a single putative causal agent and have failed to recognise that different environmental agents are often correlated. 2. Darwin suggested that although trait variation across populations is often associated with abiotic variation, evolution is more likely to be driven by biotic factors correlated with the abiotic variation. This hypothesis has received little explicit attention. 3. We use structural equation modelling to quantify the relative importance of abiotic (pH, metal concentrations) and biotic (competition, predation) factors in the evolution of body size in three-spined sticklebacks Gasterosteus aculeatus on the island of North Uist, Scotland. We combine phenotypic data from multiple isolated populations, detailed characterisation of their environment and a common garden experiment that establishes the genetic basis of size differences. 4. Three-spined sticklebacks on North Uist show almost unprecedented intraspecific evolution of body size that has taken place rapidly (<16,000 years). The smallest fish mature at only 7% of the mass of ancestral, anadromous fish. Dwarfism is associated with reduced abundance of a smaller competitor species, the nine-spined stickleback Pungitius pungitius, and with low pH indicative of poor resource conditions. Dwarfism also tends to occur where an important predator, the brown trout Salmo trutta, is also small. The abundance of P. pungitius and the size of S. trutta are themselves related to underlying abiotic environmental variation. 5. Despite the close association between abiotic and biotic factors across populations, our results support Darwin's hypothesis that biotic factors, associated with variation in the abiotic environment, are more important in explaining evolution than is abiotic variation per se. This study demonstrates the importance of considering the relationships between environmental variables before conclusions can be drawn about the causes of (body size) evolution on islands.


[Which compressor should be used to deliver pentamidine aerosols with the Respirgard II?].
Prophylaxis against pneumonia due to Pneumocystis carinii is most often carried out using pentamidine administered as an aerosol. For reasons both of comfort and cost this technique should be developed at home or at least in an extra-hospital environment. Using the Respirgard II as the nebuliser of reference this requires a compressor. We have assessed four different compressors and compared these to pressurised oxygen used in a hospital environment. During the course of nebulisation with a pentamidine aerosol two physical factors may coincide to limit their efficacy. First the deposition of some of the particles on the walls of the apparatus and secondly the production of a particle size which is incompatible with alveolar deposition. This study showed that according to the source of compressed air: 1) the fraction of the pentamidine solution found in an aerosol at the mouthpiece varies from 29 to 62%; 2) the fraction of the aerosol whose particle size is suitable for alveolar deposition (1 to 3 microns) varies from 35 to 48%. The product of these two fractions enables an assessment of the efficiency of each apparatus: 14 to 24% of the pentamidine solution may be deposited at the alveolar level. In addition to this efficiency the duration of the session (from 25 to 50 minutes) for each machine should be taken into consideration when considering the choice of the compressor to be coupled with the Respirgard II in order to improve the comfort and therefore the compliance to the treatment.


Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders.
Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field.


Landscape genetics of the blotched tiger salamander (Ambystoma tigrinum melanostictum).
The field of landscape genetics has great potential to identify habitat features that influence population genetic structure. To identify landscape correlates of genetic differentiation in a quantitative fashion, we developed a novel approach using geographical information systems analysis. We present data on blotched tiger salamanders (Ambystoma tigrinum melanostictum) from 10 sites across the northern range of Yellowstone National Park in Montana and Wyoming, USA. We used eight microsatellite loci to analyse population genetic structure. We tested whether landscape variables, including topographical distance, elevation, wetland likelihood, cover type and number of river and stream crossings, were correlated with genetic subdivision (F(ST)). We then compared five hypothetical dispersal routes with a straight-line distance model using two approaches: (i) partial Mantel tests using Akaike's information criterion scores to evaluate model robustness and (ii) the BIOENV procedure, which uses a Spearman rank correlation to determine the combination of environmental variables that best fits the genetic data. Overall, gene flow appears highly restricted among sites, with a global F(ST) of 0.24. While there is a significant isolation-by-distance pattern, incorporating landscape variables substantially improved the fit of the model (from an r2 of 0.3 to 0.8) explaining genetic differentiation. It appears that gene flow follows a straight-line topographic route, with river crossings and open shrub habitat correlated with lower F(ST) and thus, decreased differentiation, while distance and elevation difference appear to increase differentiation. This study demonstrates a general approach that can be used to determine the influence of landscape variables on population genetic structure.


Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS.
Dendritic cells (DCs) are the sentinels of the mammalian immune system, characterized by a complex maturation process driven by pathogen detection. Although multiple studies have described the analysis of activated DCs by transcriptional profiling, recent findings indicate that mRNAs are also regulated at the translational level. A systematic analysis of the mRNAs being translationally regulated at various stages of DC activation was performed using translational profiling, which combines sucrose gradient fractionation of polysomal-bound mRNAs with DNA microarray analysis. Total and polysomal-bound mRNA populations purified from immature, 4 h and 16 h LPS-stimulated human monocyte-derived DCs were analyzed on Affymetrix microarrays U133 2.0. A group of 375 transcripts was identified as translationally regulated during DC-activation. In addition to several biochemical pathways related to immunity, the most statistically relevant biological function identified among the translationally regulated mRNAs was protein biosynthesis itself. We singled-out a cluster of 11 large ribosome proteins mRNAs, which are disengaged from polysomes at late time of maturation, suggesting the existence of a negative feedback loop regulating translation in DCs and linking ribosomal proteins to immuno-modulatory function. Our observations highlight the importance of translation regulation during the immune response, and may favor the identification of novel protein networks relevant for immunity. Our study also provides information on the potential absence of correlation between gene expression and protein production for specific mRNA molecules present in DCs.


Regressive evolution in the Mexican cave tetra, Astyanax mexicanus.
The evolutionary forces driving the reduction of eyes and pigmentation in cave-adapted animals are unknown; Darwin famously questioned the role of natural selection in eye loss in cave fishes: "As it is difficult to imagine that eyes, although useless, could be in any way injurious to animals living in darkness, I attribute their loss wholly to disuse"[1]. We studied the genetics of eye and pigmentation regression in the Mexican cave tetra, Astyanax mexicanus, by mapping and quantitative trait loci (QTL) analysis. We also mapped QTL for the putatively constructive traits of jaw size, tooth number, and numbers of taste buds. The data suggest that eyes and pigmentation regressed through different mechanisms. Cave alleles at every eye or lens QTL we detected caused size reductions, consistent with evolution by natural selection but not with drift. QTL polarities for melanophore number were mixed, however, consistent with genetic drift. Arguments against a role for selection in the regression of cave-fish eyes cited the insignificant cost of their development [2, 3], but we argue that the energetic cost of their maintenance is sufficiently high for eyes to be detrimental in the cave environment. Regression can be caused either by selection or drift.


[Retinal-sensitized photo-oxidation of rhodopsin].
Kinetics of retinal photosensitized initiation of radicals of sulfhydryl groups of cysteine and rhodopsin is investigated by spin trapping. Photooxidation of both systems is the result of free radical mechanism. Photooxidation of SH-groups proceeds both with singlet oxygen participation and by direct interaction of photosensitizer with the substrate. The rate constants of these reactions are measured. The rate constant with oxygen participation (K0 = 1.1 X 10(9) M-1 S-1) is higher than the one without oxygen (K = 2.5 X 10(8) M-1 S-1) correspondingly. The lifetime of retinal triplet state in photoreceptor membrane is tau = 4 X 10(-6) s.


Post-weaning selenium and folate supplementation affects gene and protein expression and global DNA methylation in mice fed high-fat diets.
Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. Selenium and folate are two compounds which influence epigenetic mechanisms. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health. Female offspring of mothers fed the experimental diet were either maintained on this diet (HF-low-low), or weaned onto a high-fat diet with sufficient levels of selenium and folate (HF-low-suf), for 8 weeks. Gene and protein expression, DNA methylation, and histone modifications were measured in colon and liver of female offspring. Adequate levels of selenium and folate post-weaning affected gene expression in colon and liver of offspring, including decreasing Slc2a4 gene expression. Protein expression was only altered in the liver. There was no effect of adequate levels of selenium and folate on global histone modifications in the liver. Global liver DNA methylation was decreased in mice switched to adequate levels of selenium and folate, but there was no effect on methylation of specific CpG sites within the Slc2a4 gene in liver. Post-weaning supplementation with adequate levels of selenium and folate in female offspring of mice fed high-fat diets inadequate in selenium and folate during gestation and lactation can alter global DNA methylation in liver. This may be one factor through which the negative effects of a poor diet during early life can be ameliorated. Further research is required to establish what role epigenetic changes play in mediating observed changes in gene and protein expression, and the relevance of these changes to health.


Factors Associated with Breast Cancer Screening Adherence among Church-Going African American Women.
Relative to White women, African American/Black women are at an increased risk of breast cancer mortality. Early detection of breast cancer through mammography screening can mitigate mortality risks; however, screening rates are not ideal. Consequently, there is a need to better understand factors associated with adherence to breast cancer screening guidelines to inform interventions to increase mammography use, particularly for groups at elevated mortality risk. This study used the Andersen Behavioral Model of Health Services Use to examine factors associated with adherence to National Comprehensive Cancer Network breast cancer screening guidelines amongst 919 African American, church-going women from Houston, Texas. Logistic regression analyses measured associations between breast cancer screening adherence over the preceding 12 months (adherent or non-adherent) and predisposing (i.e., age, education, and partner status), enabling (i.e., health insurance status, annual household income, employment status, patient-provider communication, and social support), and need (i.e., personal diagnosis of cancer, family history of cancer, and risk perception) factors, separately and conjointly. Older age (predisposing: OR = 1.015 (1.007-1.023)), having health insurance and ideal patient-provider communication (enabling: OR = 2.388 (1.597-3.570) and OR = 1.485 (1.080-2.041)), and having a personal diagnosis of cancer (need: OR = 2.244 (1.058-4.758)) were each associated with greater odds of screening adherence. Only having health insurance and ideal patient-provider communication remained significantly associated with screening adherence in a conjoint model; cancer survivorship did not moderate associations between predisposing/enabling factors and screening adherence. Overall, results suggest that interventions which are designed to improve mammography screening rates amongst African American women might focus on broadening health insurance coverage and working to improve patient-provider communication. Implications for multi-level intervention approaches, including the role of churches in their dissemination, are proposed.


Video-assisted thoracoscopic surgery for malignant pleural effusions.
To evaluate the efficacy of video-assisted thoracoscopic surgery (VATS) in the diagnosis and treatment of malignant pleural effusions (MPE) and to assess the results and complications of the procedure. A total of 61 patients with the diagnosis of malignant pleural effusion were assessed retrospectively between 2004 - 2010, 25 women (40.9%) and 36 men (59.1%), with an age range of 18-78 (mean: 61.3). Video-thoracoscopic surgery was performed under general anesthesia or with local anesthesia in sedated patients. No intraoperative complications were observed. In 6 cases, prolonged air leak developed. Pleurodesis was successfully implemented in malignant cases. The chest tube was removed when the amount of fluid was less 50 cc/24 h. The duration of drainage was significantly shorter in patients in whom VATS was performed. We believe that VATS is an effective method in the diagnosis and palliative treatment of cases with malignant pleural effusions.


Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids.
Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.


Myeloid Cell and Transcriptome Signatures Associated With Inflammation Resolution in a Model of Self-Limiting Acute Brain Inflammation.
Inflammation contributes to tissue repair and restoration of function after infection or injury. However, some forms of inflammation can cause tissue damage and disease, particularly if inappropriately activated, excessive, or not resolved adequately. The mechanisms that prevent excessive or chronic inflammation are therefore important to understand. This is particularly important in the central nervous system where some effects of inflammation can have particularly harmful consequences, including irreversible damage. An increasing number of neurological disorders, both acute and chronic, and their complications are associated with aberrant neuroinflammatory activity. Here we describe a model of self-limiting acute brain inflammation optimized to study mechanisms underlying inflammation resolution. Inflammation was induced by intracerebral injection of lipopolysaccharide (LPS) and the temporal profile of key cellular and molecular changes were defined during the progression of the inflammatory response. The kinetics of accumulation and loss of neutrophils in the brain enabled well-demarcated phases of inflammation to be operatively defined, including induction and resolution phases. Microglial reactivity and accumulation of monocyte-derived macrophages were maximal at the onset of and during the resolution phase. We profiled the transcriptome-wide gene expression changes at representative induction and resolution timepoints and used gene coexpression network analysis to identify gene clusters. This revealed a distinct cluster of genes associated with inflammation resolution that were induced selectively or maximally during this phase and indicated an active programming of gene expression that may drive resolution as has been described in other tissues. Induction of gene networks involved in lysosomal function, lipid metabolism, and a comparative switch to MHC-II antigen presentation (relative to MHC-I during induction) were prominent during the resolution phase. The restoration and/or further induction of microglial homeostatic signature genes was notable during the resolution phase. We propose the current model as a tractable reductionist system to complement more complex models for further understanding how inflammation resolution in the brain is regulated and as a platform for in vivo testing/screening of candidate resolution-modifying interventions. Our data highlight how resolution involves active cellular and transcriptome reprogramming and identify candidate gene networks associated with resolution-phase adaptations that warrant further study.


Fatal enterocolitis in harbour seals (Phoca vitulina) caused by infection with Eimeria phocae.
Coccidiosis due to Eimeria phocae infection has been described in harbour seals (Phoca vitulina) from the western Atlantic population, but not in any detail in seals from the eastern Atlantic population. This paper describes fatal enterocolitis due to E phocae infection in three juvenile harbour seals at a rehabilitation centre in the Netherlands in July 2003. The clinical signs were lethargy, bloody faeces, and intermittent convulsions and muscle tremors just before they died; the nervous signs resembled those of nervous coccidiosis in calves. The main pathological finding was severe, diffuse, haemorrhagic enterocolitis; there were diffuse inflammatory changes in the lamina propria of the jejunal, ileal, caecal and colonic mucosa that were associated with the presence of the sexual stages and oocysts of a coccidian species identified as E phocae. A retrospective microscopical examination of intestinal tissues from 113 harbour seals that had died between 1999 and 2004 revealed one seal that was positive for E phocae.


ATF5 regulates the proliferation and differentiation of oligodendrocytes.
The transcription factor ATF5 is expressed in cells of the embryonic and neonatal ventricular zone/subventricular zone (VZ/SVZ), and must be down-regulated for their differentiation into neurons and astrocytes. Here, we show that ATF5 plays a major role in directing oligodendrocyte development. ATF5 is expressed by oligodendrocyte precursors but is absent from mature oligodendroglia. Constitutively expressed ATF5 maintains SVZ cells and O4(+) oligodendrocyte precursors in cycle and inhibits their differentiation into oligodendrocytes in vitro and in vivo. In contrast, ATF5 loss-of-function (LOF; produced by a dominant-negative form of the protein) accelerates oligodendrocyte differentiation of O4(+) cells in vitro and of SVZ cells in vivo. Significantly, the accelerated oligodendrocyte differentiation promoted by ATF5 LOF in vivo results in aberrant migration. Thus, appropriately regulated expression of ATF5 is required for proper expansion of oligodendroglial progenitors as well as for their timely differentiation. Regulation of oligodendrocyte, astrocyte, and neuronal differentiation indicates that ATF5 operates as a general regulator of the timing of differentiation, independent of cell lineage.


Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer disease.
To identify a novel biochemical marker that precedes clinical symptoms in Alzheimer disease (AD). Using quantitative polymerase chain reaction techniques, we measured circulating cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) from study participants, selected from a cohort of 282 subjects, who were classified according to their concentrations of amyloid β1-42, total tau, and phosphorylated tau and by the presence or absence of dementia, into asymptomatic subjects at risk of AD, symptomatic patients diagnosed with sporadic AD, presymptomatic subjects carrying pathogenic PSEN1 mutations, and patients diagnosed with frontotemporal lobar degeneration (FTLD). We performed equivalent studies in a separate validation cohort of sporadic AD and FTLD patients. In addition, we measured mtDNA copy number in cultured cortical neurons from mutant amyloid precursor protein/presenilin1 (APP/PS1) transgenic mice. Asymptomatic patients at risk of AD and symptomatic AD patients, but not FTLD patients, exhibit a significant decrease in circulating cell-free mtDNA in the CSF. These observations were confirmed in the validation cohort. In addition, presymptomatic subjects carrying pathogenic PSEN1 gene mutations show low mtDNA content in CSF before the appearance of AD-related biomarkers in CSF. Moreover, mtDNA content in CSF discriminates with high sensitivity and specificity AD patients from either controls or patients with FTLD. Furthermore, cultured cortical neurons from APP/PS1 transgenic mice have fewer mtDNA copies before the appearance of altered synaptic markers. Low content of mtDNA in CSF may be a novel biomarker for the early detection of preclinical AD. These findings support the hypothesis that mtDNA depletion is a characteristic pathophysiological factor of neurodegeneration in AD.


Most Colorful Example of Genetic Assimilation? Exploring the Evolutionary Destiny of Recurrent Phenotypic Accommodation.
Evolution of adaptation requires both generation of novel phenotypic variation and retention of a locally beneficial subset of this variation. Such retention can be facilitated by genetic assimilation, the accumulation of genetic and molecular mechanisms that stabilize induced phenotypes and assume progressively greater control over their reliable production. A particularly strong inference into genetic assimilation as an evolutionary process requires a system where it is possible to directly evaluate the extent to which an induced phenotype is progressively incorporated into preexisting developmental pathways. Evolution of diet-dependent pigmentation in birds-where external carotenoids are coopted into internal metabolism to a variable degree before being integrated with a feather's developmental processes-provides such an opportunity. Here we combine a metabolic network view of carotenoid evolution with detailed empirical study of feather modifications to show that the effect of physical properties of carotenoids on feather structure depends on their metabolic modification, their environmental recurrence, and biochemical redundancy, as predicted by the genetic assimilation hypothesis. Metabolized carotenoids caused less stochastic variation in feather structure and were more closely integrated with feather growth than were dietary carotenoids of the same molecular weight. These patterns were driven by the recurrence of organism-carotenoid associations: commonly used dietary carotenoids and biochemically redundant derived carotenoids caused less stochastic variation in feather structure than did rarely used or biochemically unique compounds. We discuss implications of genetic assimilation processes for the evolutionary diversification of diet-dependent animal coloration.


Computational neuroanatomy: ontology-based representation of neural components and connectivity.
A critical challenge in neuroscience is organizing, managing, and accessing the explosion in neuroscientific knowledge, particularly anatomic knowledge. We believe that explicit knowledge-based approaches to make neuroscientific knowledge computationally accessible will be helpful in tackling this challenge and will enable a variety of applications exploiting this knowledge, such as surgical planning. We developed ontology-based models of neuroanatomy to enable symbolic lookup, logical inference and mathematical modeling of neural systems. We built a prototype model of the motor system that integrates descriptive anatomic and qualitative functional neuroanatomical knowledge. In addition to modeling normal neuroanatomy, our approach provides an explicit representation of abnormal neural connectivity in disease states, such as common movement disorders. The ontology-based representation encodes both structural and functional aspects of neuroanatomy. The ontology-based models can be evaluated computationally, enabling development of automated computer reasoning applications. Neuroanatomical knowledge can be represented in machine-accessible format using ontologies. Computational neuroanatomical approaches such as described in this work could become a key tool in translational informatics, leading to decision support applications that inform and guide surgical planning and personalized care for neurological disease in the future.


Eicosapentaenoic and docosahexaenoic acid supplementation and coronary artery calcium progression in patients with coronary artery disease: A secondary analysis of a randomized trial.
We previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of noncalcified plaque. Higher coronary artery calcium (CAC) scores and progression of CAC are associated with increased cardiovascular events and mortality. We examined the effect of EPA + DHA on CAC score. A total of 242 patients with coronary artery disease (CAD) on statin therapy were randomized to 1.86 g EPA and 1.5 g DHA daily or none (control) for 30 months. The CAC score was measured at baseline and 30-months with non-contrast, cardiac computed tomography. Both EPA + DHA and control groups had significant progression in CAC scores over 30 months (median change:183.5 vs 221.0, respectively, p < 0.001) despite a 13.6% reduction in triglyceride level with EPA + DHA. No significant difference was observed between groups for the total group, by baseline CAC scores of <100, 100-399, 400-999 and ≥1000 or quartiles of achieved levels of EPA, DHA and the omega-3 fatty acid index. Similar rates of CAC progression were noted in those on high-intensity statin compared to low- and moderate-intensity statin. EPA and DHA added to statin resulted in similar CAC progression over 30 months regardless of baseline CAC categories, statin intensity and achieved levels of EPA, DHA and the omega-3 fatty acid index.


Ocular Manifestations, Visual Field Pattern, and Visual Field Test Performance in Traumatic Brain Injury and Stroke.
To analyze ocular manifestations, visual field (VF) pattern, and VF test performance in traumatic brain injury (TBI) and stroke patients. This retrospective, cross-sectional study included 118 patients (236 eyes) with TBI and stroke who had undergone VF testing by standard automated perimetry with the central 24-2 threshold test. Clinical features including best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular manifestations, and VF test results including VF defect pattern, reliability, and global indices were analyzed and compared between the TBI and stroke patients. In TBI patients, ocular manifestations included strabismus (11.1%), cataract (4.2%), and glaucoma suspect (2.8%), whereas in stroke patients, cataract (15.2%), strabismus (8.5%), diabetic retinopathy (4.9%), extraocular movement (EOM) limitation (3.0%), glaucoma suspect (3.0%), nystagmus (2.4%), drusen (1.2%), and vitreous hemorrhage (1.2%) were found. The VF test results showed that 47 eyes (85.5%) in TBI and 86 (65.2%) in stroke had VF defect; in TBI, the scattered pattern was the most common (56.4%), followed by homonymous hemianopsia (14.5%), homonymous quadrantanopia (10.9%), and total defect (3.6%), whereas in stroke, homonymous hemianopsia was the most common (31.8%), followed by scattered pattern (16.7%), homonymous quadrantanopia (12.1%), and total defect (4.5%). Only 15 eyes (27.3%) in TBI and 32 (24.2%) in stroke showed reliable VF indices. The mean deviation (MD) was -10.5 ± 7.1 dB in TBI and -9.5 ± 6.8 dB in stroke, and the pattern standard deviation (PSD) was 4.9 ± 3.3 dB in TBI and 6.1 ± 3.9 dB in stroke, without statistically significant differences between the two groups. Various ocular manifestations were found, and a considerable proportion of patients were experiencing VF defects and showed unreliable VF test performance. Our findings suggest that accurate evaluation and rehabilitation of visual function should be a matter of greater concern and emphasis in the management of TBI and stroke patients, besides systemic diseases.


Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial.
To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG. Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months. Mortality rate ratios. 174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival. Clinical trials NCT00168597.


High sensitivity CIP2A detection for oral cancer using a rapid transistor-based biosensor module.
Oral squamous cell carcinoma (OSCC) is one of the most common lip and oral cavity cancer types. It requires early detection via various medical technologies to improve the survival rate. While most detection techniques for OSCC require testing in a centralized lab to confirm cancer type, a point of care detection technique is preferred for on-site use and quick result readout. The modular biological sensor utilizing transistor-based technology has been leveraged for testing CIP2A, and optimal transistor gate voltage and load resistance for sensing setup was investigated. Sensitivities of 1 × 10-15 g/ml have been obtained for both detections of pure CIP2A protein and HeLa cell lysate using identical test conditions via serial dilution. The superior time-saving and high accuracy testing provides opportunities for rapid clinical diagnosis in the medical space.


CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis.
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by bone erosion mediated by osteoclasts (OC). Our previous studies showed an elevated frequency of OC precursors (OCP) in PsA patients. Here, we examined if OC arise from CD16-positive monocytes in PsA. Peripheral blood mononuclear cells (PBMC) or monocytes were isolated from human peripheral blood and sorted based on CD16 expression. Sorted cells were cultured alone or with bone wafers in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Enumeration and bone erosion activity of OC were examined after culture. The effects of tumor necrosis factor-alpha (TNFalpha), OC-promoting (M-CSF plus RANKL), and dendritic cell (DC)-promoting (GM-CSF plus interleukin (IL)-4) cytokines on CD16 surface expression were examined by flow cytometry. PsA and psoriasis (Ps) subjects had a higher percentage of circulating inflammatory CD14+CD16+ cells than healthy controls (HC). Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation. PBMC of Ps and PsA had a higher frequency of cells expressing intermediate levels of CD16. OC were mainly derived from CD16+ cells in PsA. Increased CD16 expression was associated with a higher bone erosion activity in PsA. An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis. Intriguingly, TNFalpha blocked CD16 expression on a subset of CD14+ monocytes. Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.


Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy.
Currently, there is limited data on the immunogenicity and efficacy of human papillomavirus vaccines in Low and Middle income countries (LMIC). The review aims to summarize the current status from published HPV vaccine safety, immunogenicity and efficacy studies in low and middle income countries (LMIC). Electronic databases (PubMed/MEDLINE and HINARI) were searched for peer reviewed English language articles on HPV vaccination in LMIC that have so far been published from 1st January 2006 up to 30th January 2015. Eligible studies were included if they had used the bivalent (bHPV) or quadrivalent HPV (qHPV) vaccines in a LMIC and investigated safety, immunogenicity and/or efficacy. The main findings were extracted and summarized. A total of fourteen HPV vaccine studies assessing safety, Immunogenicity and efficacy of the bivalent or quadrivalent vaccines in LMIC were included. There are only ten published clinical trials where a LMIC has participated. There was no published study so far that assessed efficacy of the HPV vaccines in Sub-Saharan Africa. From these studies, vaccine induced immune response was comparable to that from results of HICs for all age groups. Studies assessing HPV vaccine efficacy of the bivalent or quadrivalent vaccine within LMIC were largely missing. Only three studies were found where a LMIC was part of a multi center clinical trial. In all the studies, there were no vaccine related serious adverse events. The findings from the only study that investigated less than three doses of the bivalent HPV-16/18 vaccine suggest that even with less than three doses, antibody levels were still comparable with older women where efficacy has been proven. The few studies from LMIC in this review had comparable safety, Immunogenicity and efficacy profiles like in HIC. Overall, the LMIC of Africa where immune compromising/modulating situations are prevalent, there is need for long term immunogenicity as well as surveillance studies for long term clinical effectiveness after two and three dose regimens.


Partnerships in healthy cities and communities: a social commitment for advanced practice nurses.
People, recognizing that health is influenced by factors affecting the broader environment, are building healthier communities locally. The principles of the Ottawa Charter for Health Promotion gave direction for the development of the Healthy Cities movement globally. Community-oriented advanced practice nurses (APNs) have skills and expertise to support community leaders in their efforts to build healthier communities. Examples of partnerships involving Healthy Cities and Communities and APNs include: community leadership development, community assessment, nurse managed services, research, and policy advocacy. Based on APN experiences in community health promotion, future challenges are suggested.