Linguistic markers of demoralization improvement in schizophrenia: A pilot study

Background and objectives Individuals with schizophrenia display language impairments involving pragmatics, semantics and syntax. Language impairments may show diagnostic specificity and could relate to the ability of engaging in psychotherapy. This pilot study sought to: (1) identify linguistic features that might differentiate individuals with schizophrenia from distressed controls without psychotic symptoms; and (2) examine the association between linguistic abilities and clinical changes during psychotherapy. Methods We recruited patients with schizophrenia and a comparison group of individuals with demoralization and distress due to cancer. Participants underwent Dignity Therapy (DT), an existentially-oriented brief psychotherapy focused on legacy and subjective dignity. Verbatim transcripts of the DT sessions were analysed using Natural Language Processing (NLP). In addition, we measured changes in levels of demoralization and dignity-related distress before and after DT, exploring the association with linguistic variables with network analysis. Results Patients with schizophrenia could be differentiated from those with cancer-related distress using only three out of 141 linguistic variables: total number of words, number of prepositional chains and conversational elements. Across groups, better levels of discourse coherence and higher number of arguments controlled by a predicate (verb “arity”) were associated with larger improvements in demoralization and, indirectly, dignity-related distress. Conclusions Reproducible linguistic markers may be able to differentiate individuals with schizophrenia from those with less severe psychopathology, and to predict better uptake of psychotherapy independent from diagnosis. Future studies should explore whether linguistic features derived from NLP may be exploited as accessible diagnostic or prognostic markers to tailor psychotherapy and other interventions in schizophrenia. (AU)

Primary HPV test screening in cervical cancer: a two-year experience of a single screening center in Latina (Italy).

OBJECTIVE: The aim of this study was to evaluate the effect and performance of the new algorithm in cervical cancer screening program in two years' experience of Latina (Italy). MATERIALS AND MTHODS: The female population was divided into two groups, the first group was referred to PAP test and the second one to hr-HPV test according to national guidelines. RESULTS: In two years the participation mean rate increased among women aged 35-64 compared to women aged 25-34. The primary PAP test positive rate and hr-HPV test positive rate were 4.0% and 5.2%, respectively. The PAP test positive rate among hr-HPV+ women decreased from 2012 to 2013. Women with hr-HPV+/PAP+ were referred immediately to colposcopy and this rate was 1.2%. The predictive positive value for CIN2+ to colposcopy was 10.9% in 2012 and 9.1% in 2013, while the detection rate for CIN2+ was 1.6% in 2012 and 1.4% in 2013. CONCLUSION: The stratification of the female population leads to a decreased inappropriate therapeutic path while the combination of hr-HPV test with PAP test in woman aged 35-64 lets obtain high levels specificity and sensitivity results.

The 16, 18, and 45 HPV infection in high grade squamous cervical lesions in primary hr-HPV test screening program.

Infection with high-risk human papillomavirus (hr-HPV) 16, 18, and 45 causes 94% of cervical carcinoma. In the present screening center the authors perform the hr-HPV test followed by Pap test to women aged 35-64 years if they result hr-HPV+. The authors' aimed to provide data regarding the genotyping test and eventually to propose this test as alternative to triage cytology. They used a genotyping test to identify HPV 16, 18, and 45 in 22 women with histological diagnosis of CIN2+, 22 women with histological diagnosis of CIN1 and 22 women hr-HPV+/Pap-. The group of CIN2+ showed the higher positivity to the test and the higher positivity to HPV 16 than other groups. Analyzing the clinical performance of the genotyping test the authors observed that the specificity was 64%. From these data they concluded that the identification of HPV 16 is predictive for high-grade lesions but this test could not be used alternatively to triage cytology.

Ezrin silencing remodulates the expression of Phosphoinositide-specific Phospholipase C enzymes in human osteosarcoma cell lines.

Ezrin, a protein belonging to the Ezrin, radixin and moesin (ERM) family, was engaged in the metastatic spread of osteosarcoma. The Protein 4.1, Ezrin, radixin, moesin (FERM) domain of Ezrin binds the membrane Phosphatydil inositol (4,5) bisphosphate (PIP2), a crucial molecule belonging to the Phosphoinositide (PI) signal transduction pathway. The cytoskeleton cross-linker function of Ezrin largely depends on membrane PIP2 levels, and thus upon the activity of related enzymes belonging to the PI-specific phospholipase C (PI-PLC) family. Based on the role of Ezrin in tumour progression and metastasis, we silenced the expression of Vil2 (OMIM *123900), the gene which codifies for Ezrin, in cultured human osteosarcoma 143B and Hs888 cell lines. After Ezrin silencing, the growth rate of both cell lines was significantly reduced and morphogical changes were observed. We also observed moderate variations both of selected PI-PLC enzymes within the cell and of expression of the corresponding PLC genes. In 143B cell line the transcription of PLCB1 decreased, of PLCG2 increased and of PLCE differed in a time-dependent manner. In Hs888, the expression of PLCB1 and of PLCD4 significantly increased, of PLCE moderately increased in a time dependent manner; the expression of PLCG2 was up-regulated. These observations indicate that Ezrin silencing affects the transcription of selected PLC genes, suggesting that Ezrin might influence the expression regulation of PI-PLC enzymes.

Neuropeptide Y reduces the expression of PLCB2, PLCD1 and selected PLC genes in cultured human endothelial cells.

Endothelial cells (EC) are the first elements exposed to mediators circulating in the bloodstream, and react to stimulation with finely tuned responses mediated by different signal transduction pathways, leading the endothelium to adapt. Neuropeptide Y (NPY), the most abundant peptide in heart and brain, is mainly involved in the neuroendocrine regulation of the stress response. The regulatory roles of NPY depend on many factors, including its enzymatic processing, receptor subtypes and related signal transduction systems, including the phosphoinositide (PI) pathway and related phospholipase C (PI-PLC) family of enzymes. The panel of expression of PI-PLC enzymes differs comparing quiescent versus differently stimulated human EC. Growing evidences indicate that the regulation of the expression of PLC genes, which codify for PI-PLC enzymes, might act as an additional mechanism of control of the PI signal transduction pathway. NPY was described to potentiate the activation of PI-PLC enzymes in different cell types, including EC. In the present experiments, we stimulated human umbilical vein EC using different doses of NPY in order to investigate a possible role upon the expression PLC genes. NPY reduced the overall transcription of PLC genes, excepting for PLCE. The most significant effects were observed for PLCB2 and PLCD1, both isoforms recruited by means of G-proteins and G-protein-coupled receptors. NPY behavior was comparable with other PI-PLC interacting molecules that, beside the stimulation of phospholipase activity, also affect the upcoming enzymes' production acting upon gene expression. That might represent a mode to regulate the activity of PI-PLC enzymes after activation.

Lypopolysaccharide downregulates the expression of selected phospholipase C genes in cultured endothelial cells.

The signaling system of phosphoinositides (PI) is involved in a variety of cell and tissue functions, including membrane trafficking, ion channel activity, cell cycle, apoptosis, differentiation, and cell and tissue polarity. Recently, PI and related molecules, such as the phosphoinositide-specific phospholipases C (PI-PLCs), main players in PI signaling were supposed to be involved in inflammation. Besides the control of calcium levels, PI-PLCs contribute to the regulation of phosphatydil-inositol bisphosphate metabolism, crucial in cytoskeletal organization. The expression of PI-PLCs is strictly tissue specific and evidences suggest that it varies under different conditions, such as tumor progression or cell activation. In a previous study, we obtained a complete panel of expression of PI-PLC isoforms in human umbilical vein endothelial cells (HUVEC), a widely used experimental model for endothelial cells. In the present study, we analyzed the mRNA concentration of PI-PLCs in lipopolysaccharide (LPS)-treated HUVEC by using the multiliquid bioanalyzer methodology after 3, 6, 24, 48, and 72 h from LPS administration. Marked differences in the expression of most PI-PLC codifying genes were evident.

Expression of phosphoinositide-specific phospholipase C enzymes in human skin fibroblasts.

Fibroblasts are involved in a number of functions regulated by different signal transduction pathways, including the phosphoinositide (PI) signaling system and related converting enzymes, such as phosphoinositide-specific phospholipase C (PI-PLC). The PI-PLC family comprises crucial effector enzymes in the PI signal transduction pathway. Once activated, PI-PLC cleaves an important membrane PI, the phosphatidylinositol (4,5) bisphosphate into inositol trisphosphate and diacylglycerol-both are crucial molecules in the transduction of signals. The activity of selected PI-PLC enzymes was reported in fibroblasts, although the complete panel of expression was not available. Each cell type expresses a group of selected PI-PLC isoforms, and knowledge of the panel of expression is a necessary and preliminary tool to address further studies. In the present study, we delineated the expression panel of PI-PLC enzymes in human skin fibroblasts. PI-PLC ß1, PI-PLC ß3, PI-PLC ß4, PI-PLC γ1, PI-PLC γ2, PI-PLC δ1, PI-PLC δ3, PI-PLC δ4, and PI-PLC ϵ were expressed. PI-PLC ß1 was weakly expressed, PI-PLC δ4 was inconstantly expressed, and PI-PLC γ2 was weakly expressed.