P2X7 mRNA expression in non-small cell lung cancer: MicroRNA regulation and prognostic value

The human P2X7 receptor is significant and exhibits several functions in neoplasia. At present, little is known with regard to its regulation. P2X7 expression may be regulated post-transcriptionally and putative microRNA (miRNA) binding sites are considered to be involved. The aim of this study was to determine whether miRNAs (miR-21, let-7 g and miR-205) regulate P2X7 mRNA stability. In addition, the impact of P2X7 expression in patients with non-small cell lung cancer (NSCLC) was investigated. P2X7 mRNA and mature Let-7 g, miR-21, and miR-205 expression levels were quantified in 96 NSCLC cases using quantitative reverse transcription polymerase chain reaction. In all samples, epidermal growth factor receptor and K-Ras mutational analysis was also performed. Samples with low P2X7 expression were found to exhibit a higher fold change in miR-21 expression when compared with samples exhibiting high P2X7 expression. Significantly higher miR-21 expression was observed in the tumors of NSCLC patients with a K-Ras mutation when compared with patients who had K-Ras wild-type tumors (P=0.003). Additionally, to evaluate the association between P2X7 expression and prognosis in NSCLC patients, survival analysis was performed using the Kaplan-Meier method. A significant difference in the progression-free survival and overall survival in the NSCLC patients with high P2X7 expression was identified, when compared with that of patients with low expression (P=0.03 and P=0.02, respetively). Therefore, we hypothesized that high levels of miR-21 expression in NSCLC patients with K-Ras mutations may be regulated by a complex circuit, including P2X7 downregulation and together these processes may promote tumor progression

Mentalization, attachment, and defense mechanisms: A Psychodynamic Diagnostic Manual-2-oriented empirical investigation

Mentalizing capacities depends on the quality of primary attachment interactions with caregivers who thinks of the child as a subject with mental states. Operationalized as reflective functioning, mentalization is crucial for regulating emotions and developing of a coherent sense of identity, for interacting with individuals making sense to own and others mental states, and for distinguishing internal and external realities without distortions. Although the clinical literature on interplay between mentalization, attachment, and emotional regulation is rich, the empirical research is limited. This study sought to explore connections between reflective functioning, attachment styles, and implicit emotion regulation, operationalized as defense mechanisms, in a group of depressive patients. Twenty-eight patients were interviewed using the adult attachment interview (AAI) and diagnosed using the Psychodynamic Chart-2 of the Psychodynamic Diagnostic Manual, Second Edition. The reflective functioning scale and the defense mechanisms rating scale Qsort were applied to AAI transcriptions to assess reflective functioning and defensive profile. Patients with secure attachment showed significantly higher levels in reflective functioning and overall defensive functioning as compared to those with insecure attachment. Good reflective functioning and secure attachment correlated with mature defenses and specific defensive mechanisms that serve in better regulating affective states. Overall, the relationship between mentalization, attachment and emotion regulation lay the foundations for the delineation of defensive profiles associated with attachment patterns and reflective functioning in depressive patients. The systematic assessment of these psychological dimensions with gold-standard tools may help in tailoring personalized therapeutic interventions and promoting more effective treatments

Prevalence of psychiatric disorders in thyroid diseased patients.

Several studies have underlined the high prevalence of psychiatric symptoms and disorders in thyroid diseases. The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes, by means of a standardized instrument, i.e., the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised, Upjohn Version (SCID-UP-R). The results showed higher rates of panic disorder, simple phobia, obsessive-compulsive disorder, major depressive disorder, bipolar disorder and cyclothymia in thyroid patients than in the general population. These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Response to erlotinib in a patient with lung adenocarcinoma harbouring the EML4-ALK translocation: A case report.

Lung cancer is the leading cause of cancer-associated mortality worldwide, and the mainstay of treatment remains to be personalised therapy. Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have been reported to exert a significant impact in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harbouring mutations in the EGFR gene. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation has been described in a subset of patients with NSCLC and possesses potent oncogenic activity. This translocation represents one of the most novel molecular targets in the treatment of NSCLC. Patients who harbour the EML4-ALK rearrangement possess lung tumours that lack EGFR or K-ras mutations. The present study reports the case of a patient possessing the EML4-ALK rearrangement that was initially treated with erlotinib and achieved a lasting clinical response. To the best of our knowledge, the current study is the first report of a clinical response to EGFR-TKI in a patient with lung adenocarcinoma harbouring the EML4-ALK fusion gene, but no EGFR mutations. However, as the disease progressed, the ALK gene status of the tumour was investigated, and based upon a positive result, the patient was treated with crizotinib and achieved a complete response. In conclusion, the present study suggests that the EML4-ALK rearrangement is not always associated with resistance to EGFR-TKIs. Further studies are required to clarify the biological features of these tumours and to investigate the mechanisms underlying the primary resistance to EGFR-TKIs when the EML4-ALK rearrangement is present

INDOLE AMIDE DERIVATIVES: SYNTHESIS, STUCTURE-ACTIVITY RELATIONSHIPS AND MOLECULAR MODELLING STUDIES OF A NEW SERIES OF HISTAMINE H1-RECEPTOR ANTAGONISTS.

A number of indole amide derivatives bearing a basic side chain, in which the indole ring replaces the isoster benzimidazole nucleus typical of some well-known antihistamines, were prepared and tested for their H1-antihistaminic activity. The 1-benzyl-3-indolecarboxamides 32–42 showed antihistaminic (H1) activity (pA2 6–8); the 3-indolylglyoxylylamides 7–16 and the 2-indolecarboxamides 48–56 showed little or no activity. Insertion of the basic side chain of the active 3-indolecarboxamide derivatives into a piperazine ring (compounds 57–59) led to a dramatic loss of activity. All the active compounds proved to be competitive antagonists, since the values of the regression slope were not statistically different from 1. The most active compounds, 32, 33, 38–41, were also tested both in vitro for their anticholinergic activity and in vivo for their ability to antagonize histamine-induced cutaneous vascular permeability in rats. The biological results and the structure–activity relationships of the novel compounds are discussed in the light of molecular modelling studies, taking the molecule of astemizole as a model, and referring to proposed H1-receptor pharmacophore model

CDI/THREDDS interoperability in the SeaDataNet framework

Abstract. SeaDataNet is an EU funded project aiming to create and operate a pan-European, marine data infrastructure for managing the large and diverse datasets (i.e. temperature, salinity current, sea level, chemical, physical and biological properties) collected by the oceanographic fleets and the new automatic observation systems. In order to make the SeaDataNet system compliant with the INSPIRE Implementing Rules for discovery service, an ISO 19139 encoding of the SeaDataNet Common Data Index (CDI) metadata model was defined. Moreover, the problem of heterogeneous data sources has been addressed. In fact, a widely used system of SeaDataNet partners and oceanographic-marine community is THREDDS/OPeNDAP; this raises up the problem of federating into SeaDataNet framework THREDDS/OPeNDAP systems as well. In this paper we describe an interoperability framework to access resources (i.e. data and services) that are available through CDI and THREDDS/OPeNDAP services. The proposed solution implements a common catalog interface to discover and access the two heterogeneous resources in a common way. This catalog service is fully distributed and implements international standards as far as geospatial information discovery and query are concerned. The developed solution is called GI-cat and was experimented in the framework of the SeaDataNet European project

Paroxetine efficacy in stuttering treatment.

Stuttering is usually developmental, with onset at 4 to 5 years of age, and sometime may have a genetic component; among the possible cause of stuttering, response to conflicts, fears, neurosis, organic models, and learning models have been proposed (Andrews et al., 1983). Stuttering can be neurogenic (or acquired) as a result of stroke, head injury and degenerative or metabolic brain damage (Grant et al., 1999)