Characterization of a new trabectedin-resistant myxoid liposarcoma cell line that shows collateral sensitivity to methylating agents.

Myxoid Liposarcomas (MLS), characterized by the expression of FUS-CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402-91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402-91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402-91/ET cells showed collateral sensitivity to temozolomide due to the lack of O(6) -methylguanine-DNA-methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402-91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS-CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS-CHOP detachment from DNA. Here we report that, in contrast, in 402-91/ET cells, FUS-CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic-program such as c/EBPα and ß, in 402-91 but not in 402-91/ET cell lines. The collateral sensitivity of 402-91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin.

Microstructure of mineralized tissues in human primary teeth.

UNLABELLED: The aim of this study was to analyze the structural characteristics of the mineralized dental tissues--enamel, dentin and cementum--in primary teeth and to correlate the histological aspects observed in function of the dental type--single-rooted or multi-rooted. METHOD: Eighteen human primary noncarious teeth were sectioned in facial-lingual (single-rooted) and mesio-distal direction (multi-rooted). One to three samples from each tooth were obtained. The samples were prepared by the ground technique and analyzed under light microscopy at different magnifications. A quantitative and descriptive analysis of the morphology of the mineralized tissues was performed. RESULTS: Spindles, tufts and lamellae were consistently observed mainly in the occlusal surface of the primary molars. The scalloped pattern of the dentinoenamel junction was not always present. The same was seen for zones of interglobular dentin. Dead tracts in dentin and tertiary dentin were observed mainly in single-rooted teeth below areas of dental attrition. Areas of cellular and acellular cementum were observed in the two dental types. CONCLUSIONS: Primary teeth have some structural peculiarities and these should be investigated concerning the clinical repercussion.

Clinical and personality profile of depressed suicide attempters: A preliminary study at the open-door policy Mood Disorder Unit of San Raffaele Hospital.

Suicidal behavior is a complex phenomenon with high rates among psychiatric inpatients. Mood disorders and personality dysfunctions represent relevant risk factors for suicides attempts and suicidal ideation. Our study aims to investigate the role of the co-occurrence of clinical variables (duration of depressive state, previous suicide attempts), socio-demographic variables (gender, employment and civil status) and narcissistic personality features in the suicide risk of admitted psychiatric patients affected by a mood disorder. The sample was composed of 93 patients consecutively admitted in an open ward psychiatric Unit. Forty-eight participants had a positive history of previous suicide attempts: the suicide attempters (SA) were mostly female, unemployed and married. The SA group were observed to have suffered from a depressive episode with a longer duration; moreover in the SA group, the presence of active suicidal ideation was significantly related to a higher number of previous suicide attempts. In the whole sample, suicidal ideation was significantly related to narcissistic vulnerability personality features. Using a multidimensional approach, the present study allows a preliminary profiling of patients at risk for suicidal behavior during hospitalization.

All-optical control of long-lived nuclear spins in rare-earth doped nanoparticles.

Nanoscale systems that coherently couple to light and possess spins offer key capabilities for quantum technologies. However, an outstanding challenge is to preserve properties, and especially optical and spin coherence lifetimes, at the nanoscale. Here, we report optically controlled nuclear spins with long coherence lifetimes (T2) in rare-earth-doped nanoparticles. We detect spins echoes and measure a spin coherence lifetime of 2.9 ± 0.3 ms at 5 K under an external magnetic field of 9 mT, a T2 value comparable to those obtained in bulk rare-earth crystals. Moreover, we achieve spin T2 extension using all-optical spin dynamical decoupling and observe high fidelity between excitation and echo phases. Rare-earth-doped nanoparticles are thus the only nano-material in which optically controlled spins with millisecond coherence lifetimes have been reported. These results open the way to providing quantum light-atom-spin interfaces with long storage time within hybrid architectures.

A prospective multicentre study of healthcare provider preference in rapid HIV testing kits: Determine versus INSTI.

Rapid HIV testing may circumvent the practical barriers to HIV testing in several settings. User preference of the testing kits available has been relatively underexplored. We examined healthcare provider (HCP) ratings of two validated rapid testing kits in clinical practice. From 1 July to 1 December 2012 we prospectively recruited HCPs (clinic nurses) from three outpatient clinics linked to Lausanne University Hospital, Lausanne, Switzerland. The HCPs had experience in taking blood samples but varying experience in rapid HIV testing. Participating HCPs performed rapid HIV testing using Determine™ Combo (DETE) or INSTI™ (INSTI), according to a predefined randomization sequence, and rated practical aspects of each test using a Likert scale. Seventeen HCPs of 23 approached (74%) were eligible and agreed to participate, performing a total of 336 HIV tests. Globally, the testing procedure was rated as easy or very easy by 97% (DETE) to 99% (INSTI) of tests performed. Among experienced HCPs, DETE was rated easier than INSTI for kit storage (p < 0.001) and blood collection ( P = 0.012) while INSTI was rated easier than DETE for blood application ( P = 0.001) and test interpretation ( P = 0.005). Among less experienced HCPs, both tests performed equally with the exception of test interpretation ( P < 0.001) and overall ease of use ( P = 0.05) in favour of INSTI. Of all HCPs, 94% stated they would recommend INSTI over DETE based on the time to result, ease of test interpretation and overall ease of use. Rapid HIV testing was considered easy to perform, even by inexperienced nursing staff. Whilst both tests were considered easy to use, the HCPs in this study preferred INSTI to DETE overall, due to rapid time to result, ease of test interpretation and general ease of use.

Effects of personality on metabolic control in IDDM patients.

OBJECTIVE: The aim of this study was to evaluate the relationship between poor metabolic control and maladaptive personality traits (according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised) in an adult-onset insulin-dependent diabetes mellitus sample group (n = 77). RESEARCH DESIGN AND METHODS: Metabolic control was evaluated through glycosylated hemoglobin (HbA1c). Personality traits were assessed with the Personality Diagnostic Questionnaire-Revised, a self-administered questionnaire. Residual pancreatic secretion (fasting serum C-peptide) was also evaluated. RESULTS: Principal components analysis revealed three personality profiles: "withdrawn-suspicious" (P1), "dramatic-dependent" (P2), and "aggressive-irresponsible" (P3). Multiple linear regression analysis showed that C-peptide levels and P2 personality profiles were significant and independent predictors of HbA1c plasma levels: P2 predicted high HbA1c values and C-peptide predicted low HbA1c levels. CONCLUSIONS: These data suggest that a P2 personality profile is a significant predictor of poor metabolic control.

A psychometric-genetic study of schizotypal disorder.

This study aimed to clarify the structure and the etiological constituents of schizotypal disorder (SPD) by directly interviewing pairs of twins. A latent class analysis was applied to each individual's outcome for specified SPD items, such that each subject's phenotype could be redefined in terms of individual probabilities of class membership. Intraclass correlations were then calculated for each twin pair, and a standard univariate twin model applied. The best latent class analysis solution encompassed a model with four latent classes (three latent classes of SPD subjects, one of non-SPD). The intraclass correlations revealed a moderate to high heritability for two out of three SPD classes and for the modal class (a class composed of subjects that possessed a conditional probability of belonging to any of the SPD classes). Model fittings revealed considerable variation in the extent to which the different classes of SPD were influenced by additive genetic constituents or non-genetic factors. Although these data confirm the importance of genetic contributors in determining liability to SPD and the schizophrenia spectrum, they indicate that there is a relationship between psychometric multidimensionality and etiological heterogeneity in SPD.

Latent class analysis of DSM-IV schizotypal personality disorder criteria in psychiatric patients.

The aim of the study was to evaluate the latent structure of DSM-IV schizotypal personality disorder (SPD) diagnostic criteria. The sample consisted of 564 consecutively admitted inpatients and outpatients. Exploratory latent class analysis identified a four-class model as the best fitting model for DSM-IV SPD criteria. The first of the SPD latent classes was mainly characterized by odd thinking, inappropriate affect, and interpersonal features; the second class by cognitive/perceptual difficulties; the third class by paranoid features; and the fourth class by absence of SPD features. The conditional probability pattern of the fourclass solution could be safely replicated across confounder strata. Unlike previous findings, oddness, aloofness, and social withdrawal, rather than positive symptoms, best characterized SPD even in clinical samples.

Personality disorders and psychopathologic symptoms in patients with androgenetic alopecia.

BACKGROUND AND DESIGN: The few articles published on the interactions between psychological factors and alopecia seem to yield contrasting results. To assess the relationships between alopecia, gender, Diagnostic Statistical Manual of Mental Disorders, Revised Third Edition personality disorders, and psychopathologic symptoms reactive to alopecia, we administered the Personality Disorders Questionnaire-Revised and the Symptoms Checklist-90 to a randomly selected sample of 116 outpatients with androgenetic alopecia. RESULTS: The prevalence of personality disorders in subjects with androgenetic alopecia proved to be significantly higher than the prevalence of such diagnoses in the general population. Women did not show a higher prevalence of personality disorders or more psychopathologic symptoms than men. The factor analysis demonstrated the existence of three personality profiles (F1, F2, and F3) significantly and specifically associated with the subject's gender and with the psychopathologic reactive symptoms, measured using the Symptoms Checklist-90. CONCLUSIONS: The most important factor in developing a psychopathologic reaction to alopecia seems to be the presence of a Diagnostic Statistical Manual of Mental Disorders, Revised Third Edition personality disorder and not the subject's gender.

The pharmacokinetics of intravenous estradiol--a preliminary study.

Estradiol USP was extemporaneously compounded for intravenous administration. Eight postmenopausal women were randomized to receive one of four estradiol dosages. Serum estradiol concentrations were determined at frequent intervals after single bolus dosing. The concentration-time profile was stripped and fit, and pharmacokinetic values were generated. Approximate dosage proportionality was seen with area under the curve, the terminal half-life was 27.45+/-5.65 minutes, and volume of distribution was very low (0.082+/-0.015 L/kg). Estradiol was well tolerated by all study participants.

Borderline Personality Disorder and childhood sexual abuse: a meta-analytic study.

A meta-analysis of the published literature was performed to evaluate the common effect size (r) of the association between childhood sexual abuse (CSA) and Borderline Personality Disorder (BPD). An online search from 1980 to 1995 was used to gather published papers. r coefficient was used as an effect size measure, and 21 studies were retrieved. A moderate pooled r (.279) for the association between CSA and BPD was observed. Pooled effect size estimates were also obtained for CSA parameters. No significant effect of moderators was evidenced. The results of this study did not support the hypothesis that CSA is a major psychological risk factor or a causal antecedent of BPD.

A psychometric study of DSM-IV passive-aggressive (negativistic) personality disorder criteria.

The passive-aggressive (negativistic) personality disorder (PAPD) is one of the most controversial personality disorders. In order to assess DSM-IV PAPD psychometric properties and comorbidity pattern in a mixed psychiatric sample, 379 consecutively admitted in- and outpatients were administered SCID-II, Version 2.0. Confirmatory factor analysis showed that DSM-IV PAPD is a unidimensional construct with adequate internal consistency (K-R 20 = .85). A strong, specific association (odds ratio = 10.38, 95% CI = 4.83-22.30) was observed between DSM-IV PAPD and narcissistic personality disorder (NPD). Confirmatory factor analysis showed that DSM-IV PAPD should be considered as a subtype of a broader narcissistic disorder.

Brief communication: criterion validity of the Personality Diagnostic Questionnaire-4+ (PDQ-4+) in a mixed psychiatric sample.

Three hundred consecutively admitted in- and outpatients were administered the Personality Diagnostic Questionnaire-4+ (PDQ-4+). The Structured Clinical Interview for DSM-IV Axis II Personality Disorders, Version 2.0 (SCID-II) was used as the external diagnostic standard for personality disorder (PD) assessment. SCID-II was administered blind to PDQ-4+ scores. Low agreement between PDQ-4+ and SCID-II was observed for both dimensional and categorical PD evaluations. Receiver operating characteristic (ROC) analysis showed a definitively satisfactory discriminatory capability only for two PDQ-4+ PD scales (dependent, and antisocial). In agreement with previous studies, these results showed that PDQ-4+ was not a substitute for a structured diagnostic interview.

Temperament, character, and attachment patterns in borderline personality disorder.

The aim of this study was to assess the specificity of the association between temperamental vulnerability, character deficits, and Borderline personality disorder (BPD), controlling for the effects of attachment patterns. A total of 44 BPD patients were compared with 98 non-BPD patients with other cluster B Personality Disorder (PD) diagnoses, 39 patients with any cluster A or cluster C PD diagnoses, 70 patients with no PD diagnosis, and 206 nonclinical patients. All patients were administered the Temperament and Character Inventory, the Parental Bonding Instrument, and the Attachment Style Questionnaire. Multivariate and univariate tests showed that BPD patients differed significantly from all control groups on Novelty Seeking and Cooperativeness. These differences remained significant when controlling for the effect of attachment.

Interrater reliability and internal consistency of the structured clinical interview for DSM-IV axis II personality disorders (SCID-II), version 2.0.

Interrater reliability and internal consistency of the SCID-II 2.0 was assessed in a sample of 231 consecutively admitted in- and outpatients using a pairwise interview design, with randomized rater pairing and blind interview assessment. Interrater reliability coefficients ranged from .48 to .98 for categorical diagnosis (Cohen kappa), and from .90 to .98 for dimensional judgements (Intraclass correlation coefficient). Internal consistency coefficients were satisfactory (.71-.94). The results suggest that the SCID-II 2.0 has adequate interrater and internal consistency reliability.

Antiinflammatory effects of seaprose-S on various inflammation models.

The antiinflammatory activity of seaprose-S in different experimental models involving different biochemical mediators of inflammation was investigated. In vivo experiments were performed using male Sprague-Dawley rats and in vitro experiments were performed using articular cartilage explants of pig joints. In acute experimental models of inflammation, 0.5, 1 or 2 mg/kg of seaprose-S was injected intravenously (i.v.) before challenge with inflammatory agents. In adjuvant-induced arthritis, seaprose-S was given as a 2 mg/kg i.v. dose once a day for 4 consecutive days from day 8 after injection of the adjuvant. In cartilage-synovium cocultures, seaprose-S was incubated at a concentration of 0.001 microM and 0.05 microM. Paw volume was measured with a plethysmograph and proteoglycan synthesis was determined in articular cartilage-synovium coculture by incorporation of 35S-sulfate. Seaprose-S inhibited inflammation dose-dependently in carrageenan, concanavalin-A, FeCl2, nystatin-induced paw edema and in carrageenan-induced pleurisy and acetic acid-induced peritonitis. In Freund's adjuvant-induced arthritis, seaprose-S significantly reduced the primary and secondary lesions. In vitro on articular cartilage, seaprose-S increased proteoglycan synthesis in the cartilage alone and reduced the inhibition of proteoglycan synthesis in the cartilage cocultured with minced synovium.

Pharmacokinetic study of neostigmine after intranasal and intravenous administration in the guinea pig.

It is well known that the nasal route may be an effective alternative to the administration of drugs poorly absorbed via oral administration. Thus an investigation of neostigmine bioavailability after nasal administration was undertaken. The neostigmine kinetic profiles after nasal and intravenous administration in the guinea pig have been compared, and results indicate good nasal absorption of neostigmine. At the same dose, no significant differences have been noticed between the two administration routes, as the area under the curve and the bioavailability index is close to 100%. Moreover nasal administration shows a longer plasmatic elimination compared with the i.v. route (t1/2 beta e.n. = 160.04 min; t1/2 beta i.v. = 23.35 min). Nasal absorption is observed to be dose-related. The present results suggest that nasal administration of neostigmine may be an effective clinical means in Myasthenia gravis therapy.

Dextrorphan and dextromethorphan: comparative antitussive effects on guinea pigs.

Dextromethorphan, after administration, is rapidly and extensively transformed into dextrorphan. The aim of this study was to compare the cough-suppressing activity of 6, 12, 24, 48 mg/kg, i.p., of dextrorphan (dextro rotatory isomer of racemorphan) with that of dextromethorphan, using the model of citric acid-induced coughing in the unanaesthetized, unrestrained guinea pig. A significant dose-effect relationship of dextrorphan in reducing citric acid-induced cough was observed. This effect was comparable with that of dextromethorphan. However, at 48 mg/kg, i.p., dextromethorphan had a toxic effect while dextrorphan did not. Because dextrorphan is the major metabolite of dextromethorphan and has antitussive activity comparable to that of dextromethorphan, clinical use of dextrorphan is suggested.

Effects of betahistine metabolites on frog ampullar receptors.

Previous studies have demonstrated that betahistine, an histamine-like substance used widely as an anti-vertigo drug, can decrease ampullar receptor resting discharge without affecting their mechanically evoked responses. Pharmacokinetic studies have shown that this drug is transformed, mainly at the hepatic level, into aminoethylpyridine (M1), hydroxyethylpyridine (M2), then excreted with the urine as pyridylacetic acid (M3). The goal of the present study was to investigate whether betahistine metabolites are also able to affect vestibular receptor activity. Results demonstrated that, in the range tested (10(-7)-10(-2) M), M2 and M3 exerted no effect, whereas M1, at concentrations higher than 10(-6) M, was able to reduce the resting discharge of ampullar receptors without affecting the evoked responses. M1 therefore exerts effects similar to those of betahistine on ampullar receptors. This might be of some clinical interest. On the basis of our data, the hypothesis may be put forward that the anti-vertigo action of betahistine is at first achieved by betahistine itself and then sustained by M1.

Bioavailability of intranasal neostigmine: comparison with intravenous route.

The pharmacokinetics of intranasal (i.n.) neostigmine was compared with the intravenous (i.v.) route in 6 healthy volunteers with a mean age of 25.5 years and a mean weight of 65.8 kg in a crossover design. The doses used were 0.5 mg i.v. and 21.6 mg i.n. Neostigmine was determined by HPLC. The plasmatic profiles of the two routes were similar. An early peak of plasmatic concentration after i.n. administration was observed. The absolute bioequivalence of the i.n. route was ten-fold greater than the oral one.