Variation in dopamine D2 and serotonin 5-HT2A receptor genes is associated with working memory processing and response to treatment with antipsychotics

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with secondgeneration antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n¼63 and n¼54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype–phenotype relationships

Retroperitoneal liposarcoma associated with small plaque parapsoriasis

<p>Abstract</p> <p>Background</p> <p>Extremely rare cases of paraneoplastic syndromes or ectopic production of proteins associated with liposarcoma are reported in literature. Production of Granulocyte-Colony Stimulating Factor, alpha-fetoprotein, paraneoplastic pemphigus and leucocytosis, Acrokeratosis paraneoplastica (Bazex's syndrome) are reported.</p> <p>The present report describes a case of retroperitoneal liposarcoma associated with small plaque parapsoriasis. Our search in the English literature of such a kind of association did not reveal any case reported.</p> <p>Case presentation</p> <p>A 74 year male patient was admitted to our hospital because of the presence of an abdominal mass in right iliac fossa. He also complained of a two-year history of psoriasiform eruptions. The CT scan showed a retroperitoneal pelvic mass. Therefore surgical resection of the tumor was performed. After surgery, the skin eruptions disappeared completely in seven days and so a diagnosis of parapsoriasis syndrome was done.</p> <p>Conclusion</p> <p>Parallel disappearing of skin eruptions after surgery, typical clinical picture and not specific histology of the cutaneous lesions suggest the diagnosis of small plaque parapsoriasis. Therefore we propose to add Small Plaque Parapsoriasis to the list of paraneoplastic syndromes associated to liposarcoma.</p

Evidence of an interaction between FXR1 and GSK3 beta polymorphisms on levels of Negative Symptoms of Schizophrenia and their response to antipsychotics

Background: Genome-Wide Association Studies (GWASs) have identified several genes associated with Schizophrenia (SCZ) and exponentially increased knowledge on the genetic basis of the disease. In addition, products of GWAS genes interact with neuronal factors coded by genes lacking association, such that this interaction may confer risk for specific phenotypes of this brain disorder. In this regard, fragile X mental retardation syndrome-related 1 (FXR1) gene has been GWAS associated with SCZ. FXR1 protein is regulated by glycogen synthase kinase-3β (GSK3β), which has been implicated in pathophysiology of SCZ and response to antipsychotics (APs). rs496250 and rs12630592, two eQTLs (Expression Quantitative Trait Loci) of FXR1 and GSK3β, respectively, interact on emotion stability and amygdala/prefrontal cortex activity during emotion processing. These two phenotypes are associated with Negative Symptoms (NSs) of SCZ suggesting that the interaction between these SNPs may also affect NS severity and responsiveness to medication. Methods: To test this hypothesis, in two independent samples of patients with SCZ, we investigated rs496250 by rs12630592 interaction on NS severity and response to APs. We also tested a putative link between APs administration and FXR1 expression, as already reported for GSK3β expression. Results: We found that rs496250 and rs12630592 interact on NS severity. We also found evidence suggesting interaction of these polymorphisms also on response to APs. This interaction was not present when looking at positive and general psychopathology scores. Furthermore, chronic olanzapine administration led to a reduction of FXR1 expression in mouse frontal cortex. Discussion: Our findings suggest that, like GSK3β, FXR1 is affected by APs while shedding new light on the role of the FXR1/GSK3β pathway for NSs of SCZ

Quadrupole core polarization charges in the A=100 and 150 mass regions

The neutron and proton quadrupole core polarization charges are evaluated from the comparison of 0gs+ → 21+ quadrupole transition matrix elements measured by inelastic scattering of different incident probes on Mo, Pd, Cd, Nd, Sm, Gd and Dy isotopes. The resulting values, and in particular those obtained in the framework of the interacting boson model, are discussed with special attention to the evaluation of the strength of low-lying mixed-symmetry states

Clusters of galaxies : observational properties of the diffuse radio emission

Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

Smoking, season, and detection of chlamydia pneumoniae DNA in clinically stable COPD patients

BACKGROUND: The prevalence and role of Chlamydia pneumoniae in chronic obstructive pulmonary disease (COPD) remain unclear. METHODS: Peripheral blood mononuclear cells were obtained from 100 outpatients with smoking-related, clinically stable COPD, and induced sputum was obtained in 62 patients. RESULTS: Patients had mean age (standard deviation) of 65.8 (10.7) years, mean forced expiratory volume in one second of 1.34 (0.61) L, and 61 (61.0%) were male. C. pneumoniae nucleic acids were detected by nested polymerase chain reaction in 27 (27.0%). Current smoking (odds ratio {OR} = 2.6, 95% confidence interval {CI}: 1.1, 6.6, P = 0.04), season (November to April) (OR = 3.6, 95% CI: 1.4, 9.2, P = 0.007), and chronic sputum production (OR = 6.4, 95% CI: 1.8, 23.2, P = 0.005) were associated with detection of C. pneumoniae DNA. CONCLUSIONS: Prospective studies are needed to examine the role of C. pneumoniae nucleic acid detection in COPD disease symptoms and progression

Wheeze in Preschool Age Is Associated with Pulmonary Bacterial Infection and Resolves after Antibiotic Therapy

BACKGROUND: Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children. METHODOLOGY/PRINCIPAL FINDINGS: Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2-16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥ 10⁴ colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination. CONCLUSIONS/SIGNIFICANCE: Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy

The prognostic value of the suPARnostic® ELISA in HIV-1 infected individuals is not affected by uPAR promoter polymorphisms

<p>Abstract</p> <p>Background</p> <p>High blood levels of soluble urokinase Plasminogen Activator Receptor (suPAR) are associated with poor outcomes in human immunodeficiency-1 (HIV-1) infected individuals. Research on the clinical value of suPAR in HIV-1 infection led to the development of the suPARnostic^®assay for commercial use in 2006. The aim of this study was to: 1) Evaluate the prognostic value of the new suPARnostic^®assay and 2) Determine whether polymorphisms in the active promoter of uPAR influences survival and/or suPAR values in HIV-1 patients who are antiretroviral therapy (ART) naive.</p> <p>Methods</p> <p>DNA samples were collected retrospectively from 145 Danes infected with HIV-1 with known seroconversion times. In addition, plasma was collected retrospectively from 81 of these participants for use in the suPAR analysis. Survival was analysed using Kaplan Meier analysis.</p> <p>Results</p> <p>Survival was strongly correlated to suPAR levels (p < 0.001). Levels at or above 6 ng/ml were associated with death in 13 of 27 patients within a two-years period; whereas only one of 54 patients with suPAR levels below 6 ng/ml died during this period. We identified two common uPAR promoter polymorphisms: a G to A transition at -118 and an A to G transition at -465 comparative to the transcription start site. These promoter transitions influenced neither suPAR levels nor patient survival.</p> <p>Conclusion</p> <p>Plasma suPAR levels, as measured by the suPARnostic^®assay, were strongly predictive of survival in ART-naïve HIV-1 infected patients. Furthermore, plasma suPAR levels were not influenced by uPAR promoter polymorphisms.</p

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signaling

Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1435/1449 and LPS1690 appear responsible for tissue specific immune signalingpathways activation and increased virulence. The modification of lipid A to tetra-acylated1435/1449 and/or penta-acylated1690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1435/1449 and LPS1690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR 2 and TLR 4 activation. This enabless P. gingivalis to select the conditions for its entry, survival and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. Thismini review describes a number of effects that LPS1435/1449 and LPS1690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production and adverse effects on pregnancy outcome. The ability to change its LPS1435/1449 and/or LPS1690 composition may enables P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue