One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial.

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. METHODS: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. RESULTS: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). CONCLUSIONS: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia.

OBJECTIVE: Treatment resistance is a challenge for the management of schizophrenia. It is not always clear whether inadequate response is secondary to medication ineffectiveness, as opposed to medication underexposure due to non-adherence or pharmacokinetic factors. We investigated the prevalence of subtherapeutic antipsychotic plasma levels in patients identified as treatment-resistant by their treating clinician. METHOD: Between January 2012 and April 2017, antipsychotic plasma levels were measured in 99 individuals provisionally diagnosed with treatment-resistant schizophrenia by their treating clinicians, but not prescribed clozapine. Patients were followed up to determine whether they were subsequently admitted to hospital. RESULTS: Thirty-five per cent of plasma levels were subtherapeutic, and of these, 34% were undetectable. Black ethnicity (P = 0.006) and lower dose (P < 0.001) were significantly associated with subtherapeutic/undetectable plasma levels. Individuals with subtherapeutic/undetectable levels were significantly more likely to be admitted to hospital (P = 0.02). CONCLUSION: A significant proportion of patients considered treatment-resistant have subtherapeutic antipsychotic plasma levels, and this is associated with subsequent admission. The presence of subtherapeutic plasma levels may suggest a need to address adherence or pharmacokinetic factors as opposed to commencing clozapine treatment. While antipsychotic levels are not recommended for the routine adjustment of dosing, they may assist with the assessment of potential treatment resistance in schizophrenia.

DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia.

Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes. Next, we identified non-coding single-nucleotide polymorphisms (SNPs) associated with co-expression of this pathway. These SNPs were associated with regulatory genetic loci in the dorsolateral prefrontal cortex (P<0.05). We summarized their compound effect on co-expression into a Polygenic Co-expression Index (PCI), which predicted DRD2 pathway co-expression in both mRNA data sets (all P<0.05). We associated the PCI with brain activity during WM performance in two independent samples of healthy individuals (total N=368) and 29 patients with SCZ who performed the n-back task. Greater predicted DRD2 pathway prefrontal co-expression was associated with greater prefrontal activity and longer WM reaction times (all corrected P<0.05), thus indicating inefficient WM processing. Blind prediction of treatment response to antipsychotics in two independent samples of patients with SCZ suggested better clinical course of patientswith greater PCI (total N=87; P<0.05). The findings on this DRD2 co-expression pathway are a proof of concept that gene co-expression can parse SCZ risk genes into biological pathways associated with intermediate phenotypes as well as with clinically meaningful information.

Peripapillary RNFL Thickness Changes Evaluated with Spectral Domain Optical Coherence Tomography after Uncomplicated Macular Surgery for Epiretinal Membrane.

PURPOSE: To evaluate the peripapillary RNFL (p-RNFL) thickness changes after vitrectomy for epiretinal membrane (ERM). The relationship between p-RNFL thickness change and visual function was assessed. METHODS: Thirty-five eyes from 35 patients with ERM who underwent vitrectomy with internal limiting membrane (ILM) removal were included. Average p-RNFL and the four quadrants thickness were measured by spectral-domain optical coherence tomography (SD-OCT) before and at one, three, and six months after surgery. RESULTS: At six months after surgery, p-RNFL thickness of the temporal and inferior quadrant was decreased in the operated eyes compared with fellow eyes (p<0.05). Pattern standard deviation (PSD) was higher than that of fellow eyes (p = 0.002). The temporal and inferior quadrant p-RNFL thickness showed a relationship with both best-corrected visual acuity (BCVA) outcome and the six-month PSD (p<0.05, respectively). CONCLUSIONS: The selective decrease in the temporal and inferior p-RNFL thickness after vitrectomy for ERM removal could indicate inner retinal damage related to ILM peeling.

[The bilateral renal lymphoma: an incurable disease? Case report]. / Il linfoma renale bilaterale: è ancora una malattia incurabile? Case Report.

The bilateral primary renal lymphoma (PRL) is a rare disease with a high mortality rate (75% within the first year). We report the case of a fifty-three years old women observed in January 2011 for renal colic. Ultrasonography showed hypoechoic lobular formations in the kidney. Blood tests showed: creatinine 1.8 mg/dl, urea 75 mg/dl , Creatinine Clerance 35 ml/m, hemoglobinemia 11 g/dl, with blood cells 8.500/mcL, Albumin 2.8 g/dl, Beta -2 micro - 27.3/mL. Proteinuria was 0.3 g/24 hours. The CT scan showed kidneys with larger dimensions and multiple hypodense areas infiltrating the renal parenchyma with contrast-enhanced low in which kidneys had lesions similar to "leopard skin". The CT scan showed no enlarged lymph nodes. Renal biopsy showed: renal parenchyma largely occupied by infiltration of lymphoid elements, small and medium-sized, densely packed with compression of the tubular structures . Immunofluorescence for immunoglobulin (Ig) G, IgA, IgM, C3, C4, C1q, fibrinogen, kappa and lambda were negative. The bone marrow biopsy excluded lymphomatous infiltration. The histological diagnosis was "non-Hodgkin's B-cell lymphoma"; the clinical diagnosis was LRBP. The patient was treated by 6 cycles of R-CHOP-21 protocol (rituximab - endoxan, adriblastina , vincristine, prendnisone), the latter of which practiced in August 2011. The pt is currently in follow-up hematology and nephrology . The first TAC control , in October 2011, showed a complete regression of the lesions infiltrating . This finding was confirmed by two other CT scan performed in February and October 2012. The last blood tests of February 2013 showed : creatinine 1.1 mg / dl , Urea 40 mg/dl, proteinuria absent. Currently, the pt is asymptomatic and is being treated by low dose of ACE inhibitor. The bilateral PRL is considered a severe disease with one-year mortality of 75% . The successful outcome of the case described can be attributed to haematological therapy and to the early diagnosis.

Evidence that hippocampal-parahippocampal dysfunction is related to genetic risk for schizophrenia.

BACKGROUND: Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. METHOD: We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. RESULTS: Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. CONCLUSIONS: Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

Ocular traumatology in children. A retrospective study.

UNLABELLED: OBIECTIVE: This study assesses the descriptive epidemiology of children with eye injuries presenting to the Emergency Department of a non exclusive Paediatric University Hospital - First Division of Ophthalmology of "Sapienza" University of Rome - over a period of 12 years. STUDY DESIGN: A retrospective long term study of 12 years. PARTICIPANTS: All paediatric patients (up to 14 years of age) presenting with ocular injuries and hospitalized. METHODS: It was analyzed the incidence of the ocular trauma among males and females. The situation in which the trauma occurred, type of trauma (contusive or perforating), the presence of endo-bulbar foreign bodies, visual acuity outcome. RESULTS: There were 203 patients who presented to the Emergency Department in the period examined. Contusive traumas were 130 (90 males, 40 females). The perforating trauma were 73 (63 males, 10 females). The presence of an endo-bulbar foreign body was registered in 10 patients. A detailed analysis of the causes of the trauma is therefore provided. We evidence that males were almost exclusively involved in sport traumas (60 males versus 2 females), and in second instance accidental trauma is almost equally divided between two genders. CONCLUSIONS: Our retrospective study presents the paediatric cases of a non exclusive Paediatric University Hospital where 3% of ocular traumas requiring hospitalization were in children. Therefore our data could be useful in order to bring about the necessary preventive measures to minimize paediatric eye injuries.

Generation of a flat-top laser beam for gravitational wave detectors by means of a nonspherical Fabry-Perot resonator.

We have tested a new kind of Fabry-Perot long-baseline optical resonator proposed to reduce the thermal noise sensitivity of gravitational wave interferometric detectors--the "mesa beam" cavity--whose flat top beam shape is achieved by means of an aspherical end mirror. We present the fundamental mode intensity pattern for this cavity and its distortion due to surface imperfections and tilt misalignments, and contrast the higher order mode patterns to the Gauss-Laguerre modes of a spherical mirror cavity. We discuss the effects of mirror tilts on cavity alignment and locking and present measurements of the mesa beam tilt sensitivity.

Inhibitors of DNA methylation and histone deacetylation activate cytomegalovirus promoter-controlled reporter gene expression in human glioblastoma cell line U87.

The expression of many cellular genes is modulated by DNA methylation and histone acetylation. These processes can influence malignant cell transformation and are also responsible for the silencing of DNA constructs introduced into mammalian cells for therapeutic or research purposes. As a better understanding of these biological processes may contribute to the development of novel cancer treatments and to study the complex mechanisms regulating gene silencing, we established a cellular system suitable to dissect the mechanisms regulating DNA methylation and histone acetylation. For this purpose, we stably transfected the neuroblastoma cell line U87 with a cytomegalovirus promoter-driven reporter gene construct whose expression was analyzed following treatment with the DNA methylation inhibitor 5'-aza-2'-deoxycytidine or histone deacetylation inhibitor trichostatin A. Both substances reactivated the silenced cytomegalovirus promoter, but with different reaction kinetics. Furthermore, whereas the kinetics of reactivation by trichostatin A did not substantially change over the time range considered (5 days), reactivation induced by 5'-aza-2'-deoxycytidine showed profound differences between day 1 and longer time points. We showed that this effect is related to the down-regulation of DNA replication by 5'-aza-2'-deoxycytidine. Finally, we have shown that the simultaneous administration of trichostatin A and 5'-aza-2'-deoxycytidine results in reactivation of the CMV promoter according to a cooperative, not synergistic or additive, mechanism. In conclusion, our cellular system should represent a powerful tool to investigate the complex mechanisms regulating gene silencing and to identify new anticancer drugs.

Evidence for telomerase involvement in the angiogenesis of astrocytic tumors: expression of human telomerase reverse transcriptase messenger RNA by vascular endothelial cells.

OBJECT: Evidence from recent in vitro studies indicates that reactivation of telomerase, the enzyme that synthesizes the telomere ends of chromosomes, is a crucial event in the unlimited clonal expansion of endothelial cells that precedes the neoplastic conversion of these cells. It is known that high-grade gliomas express telomerase and that, in these neoplasms, proliferating endothelial cells may undergo transformational changes with development of sarcomatous components within the primitive tumor. To assess whether telomerase is involved in the endothelial cell proliferation that characterizes brain tumor angiogenesis, the authors investigated at the single-cell level the expression of messenger (m)RNA for the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) by vascular cells of astrocytic tumors. METHODS: The in situ hybridization (ISH) method was performed by processing histological sections with specific riboprobes for hTERT and for c-myc, an oncogene that is known to upregulate hTERT. Results of the ISH studies were compared with proliferative activity, as estimated by Ki-67 immunostaining. The expression of hTERT mRNA by vascular endothelial cells was related to the histological grade of the tumor because it was detected in five (29%) of 17 low-grade astrocytomas, nine (56%) of 16 anaplastic astrocytomas, and 19 (100%) of 19 glioblastomas multiforme (GBMs). Expression of c-myc mRNA was strictly correlated with that of hTERT mRNA. In low-grade astrocytomas and anaplastic astrocytomas, a dissociation was noted between hTERT mRNA expression and the proliferation rate of endothelial cells. Conversely, GBMs displayed a significant correlation between the level of hTERT mRNA expression and endothelial cell proliferation. Data from an in vitro assay in which human umbilical vein endothelial cells were stimulated to proliferate by adding vascular endothelial growth factor and an ISH study of newly formed vessels surrounding brain infarcts confirmed that expression of hTERT mRNA does not merely reflect the proliferative status of endothelial cells but represents a specific feature of brain tumor neovascularization. CONCLUSIONS: The results of this study are consistent with a role of telomerase in the angiogenesis of astrocytic tumors. Expression of hTERT mRNA by tumor vascular cells is an early event during the progression of astrocytic tumors, which precedes endothelial cell proliferation and may represent a first sign of dedifferentiation. Other than elucidating the mechanisms of tumor angiogenesis, these results encourage research on antitelomerase drugs for the treatment of malignant gliomas.

The length of telomeric G-rich strand 3'-overhang measured by oligonucleotide ligation assay.

A typical G-rich telomeric DNA strand, which runs 5'-->3' toward the chromosome ends, protrudes by several nucleotides in lower eukaryotes. In human chromosomes long G-rich 3'-overhangs have been found. Apart from the standard G-rich tail, several non-canonical terminal structures have been proposed. However, the mechanism of long-tail formation, the presence and the role of these structures in telomere maintenance or shortening are not completely understood. In a search for a simple method to accurately measure the 3'-overhang we have established a protocol based on the ligation of telomeric oligonucleotide hybridized to non-denatured DNA under stringent conditions (oligonucleotide ligation assay with telomeric repeat oligonucleotide). This method enabled us to detect a large proportion of G-rich single-stranded telomeric DNA that was as short as 24 nt. Nevertheless, we showed G-tails longer than 400 nt. In all tested cells the lengths ranging from 108 to 270 nt represented only 37% of the whole molecule population, while 56-62% were <90 nt. Our protocol provides a simple and sensitive method for measuring the length of naturally occurring unpaired repeated DNA.

Absence of association between a variant of the mast cell chymase gene and atopic dermatitis in an Italian population.

Atopic dermatitis (AD) is a chronic dermatitis which belongs to the group of atopy-related diseases together with asthma and rhinitis. IgE and mast cell chymase (MCC) play a key role in atopic or allergic inflammation of the skin. An association between AD and a genetic variant of the MCC has been reported in a Japanese population, but failure of confirmation has rendered this association questionable. We have tested for genetic association to an MCC variant in relation to AD in an Italian population. No significant association was found between AD and MCC genotypes. These data suggest that BstXI MCC polymorphism may not be involved in AD.

In situ detection of telomerase catalytic subunit mRNA in glioblastoma multiforme.

Activation of telomerase may allow unlimited cell proliferation and immortalization. One of the telomerase protein subunits has a reverse transcriptase (hTERT) activity that is essential for telomerase function and regulation. In human gliomas, telomerase is frequently associated with malignant tumor progression. In our study, we investigated the expression of hTERT at the cellular level in 34 primary de novo glioblastoma multiforme (GBM) by in situ hybridization (ISH). The expression of hTERT in tumor tissue was also assessed by RT-PCR. In addition, telomerase activity measured by telomeric repeat amplification protocol (TRAP) and telomere length polymorphism assayed by telomere restriction fragment (TRF) Southern blot were investigated. We found that all GBM, including those with negative TRAP reaction, contained abundant amounts of cytoplasmic hTERT mRNA. Interestingly, the ISH analysis revealed that the hTERT mRNA was homogeneously expressed by the whole tumor cell population in about 60% of the GBM. In the remaining cases, hTERT was absent in subsets of tumor cells. TRF analysis, which shows that both TRAP-positive and TRAP-negative de novo GBM have elongated telomeres, further supports that telomerase activity is present in all de novo GBM. Correlations with tumor size and extent of necrosis suggest that hTERT reactivation is an early event in GBM development and that telomerase activity may be lost in subpopulations of neoplastic cells during tumor progression. Finally, ISH analysis of hTERT mRNA seems to provide a prognostic parameter for primary de novo GBM.

Haemochromatosis gene mutations and risk of coronary artery disease.

The identification of mutations in the haemochromatosis gene (HFE) (C282Y and H63D) provides the unique opportunity to test whether genetic variants that are associated with tissue iron accumulation may influence the risk of coronary atherosclerosis. To this aim the prevalence of C282Y and H63D mutations was determined in 174 patients with angiographically documented CAD (>50% stenosis) and history of MI, 187 healthy free-living individuals and 142 blood donors. C282Y and H63D mutations were not found to be more frequent in coronary patients as compared to controls. Moreover, these HFE variants were unrelated to the severity of coronary atherosclerosis. These findings did not provide evidence of an association between HFE mutations and the presence of coronary atherosclerosis or its major ischaemic complications, thus indicating that HFE mutations are poor genetic markers of coronary risk.

A rare case of ceruminous tumor of the cerebellopontine angle.

In this case report we describe the development in the cerebellopontine angle of a very rare tumor, ceruminous adenoma. In the few cases described in the literature this tumor occurred in the external acoustic meatus. In four cases it developed in the cerebellopontine angle by infiltration of the petrous bone or by subcutaneous spread. In the present case no connection was found between the cerebellopontine angle and the external acoustic meatus. The most likely pathogenetic hypothesis in this case is that of a tumor of dysembryogenetic origin.

Telomerase expression in intracranial tumours: prognostic potential for malignant gliomas and meningiomas.

AIM: To evaluate the diagnostic value of telomerase expression in intracranial tumours. METHODS: 98 surgical specimens from different neoplasms were analysed by the telomeric repeat amplification protocol (TRAP) and the presence of telomerase compared with the histological diagnosis and the proliferation index. RESULTS: A high degree of positivity for telomerase activity was found in glioblastomas and atypical/anaplastic meningiomas. Telomerase activity was poorly detected in anaplastic astrocytomas. CONCLUSIONS: The TRAP assay seems to be a valuable index for identifying meningeal tumours with aggressive behaviour.