The personality profile of borderline personality disordered patients using the five-factor model of personality

The purpose of this ex post facto study is to analyze the personality profile of outpatients who met criteria for borderline personality disorder according to the Five-Factor Model of personality. All patients (N = 52) completed the International Personality Disorder Examination (IPDE) Screening Questionnaire, the Big Five Questionnaire (BFQ), the Beck Depression Inventory (BDI), and the Beck Hopelessness Scale (BHS). The results show a high comorbidity with other DSM-IV-TR Axis II disorders, in particular with those from Cluster C. The BFQ average score indicates that the outpatients who met borderline criteria score lower than controls on all five dimensions, and especially on emotional stability. Correlations were computed between the BFQ and the IPDE scales in our sample. These results suggest that specific personality profile are linked to different comorbidity patterns. More than a half of our sample has clinically significant scores on Beck's scales. Surprisingly, depression and hopelessness are neither correlated with the borderline scale, nor have an effect in the relationship between personality and personality disorders.

Soil tillage affects the community structure of mycorrhizal fungi in maize roots

In this study we tested whether communities of arbuscular mycorrhizal fungi (AMF) colonizing the roots of maize (Zea mays L.) were affected by soil tillage practices (plowing, chiseling, and no-till) in a long-term field experiment carried out in Tanikon (Switzerland). AMF were identified in the roots using specific polymerase chain reaction (PCR) markers that had been developed for the AMF previously isolated from the soils of the studied site. A nested PCR procedure with primers of increased specificity (eukaryotic, then, fungal, then AMF species or. species-grouop specific) was used. Sequencing of amplified DNA confirmed that the DNA obtained from the maize roots was of AMF origin. Presence of particular AMF species or species-group was scored as a presence of a DNA product after PCR with specific primers. We also used single-strand conformation polymorphism analysis (SSCP), of amplified DNA samples to-check if the amplification of the DNA from maize roots matched the expected profile for a particular AMF isolate with a given specific primer pair. Presence of the genus Scutellospora, in maize roots was strongly reduced in plowed and chiseled soils. Fungi from the suborder Glomineae were more prevalent colonizers of maize roots growing in plowed soils, but were also present in the roots from other tillage treatments. These changes in community of AMF colonizing maize roots might be due to (1), the differences in tolerance to the tillage-induced disruption of the hyphae among the different AMF species, (2) changes in nutrient content of the soil, (3) changes in microbial activity, or (4) changes in weed populations in response to soil tillage. This is the first report on community composition of AMF in the roots of a field-grown crop plant (maize) as affected by soil tillage.

The career indecision profile : measurement equivalence in two international samples

This study tested for the measurement equivalence of a four-factor measure of career indecision (Career Indecision Profile-65 [CIP-65]) between a U.S. sample and two international samples; one composed of French-speaking young adults from France and Switzerland and the other of Italian ado- lescents. Previous research had supported the four-factor structure of the CIP-65 in both the United States and Iceland but also showed that items on two of the four scales may be interpreted differently by young adults growing up in these two countries. This study extends previous research by testing whether the four CIP-65 factors are measured equivalently in two additional international samples. Results largely supported the configural and metric invariance of the CIP-65 in the United States and international samples, but several scales showed a lack of scalar invariance. Some explanations are offered for these findings along with suggestions for future research and implications for practice.

The neurochemical profile quantified by in vivo 1H NMR spectroscopy.

Proton NMR spectroscopy is emerging from translational and preclinical neuroscience research as an important tool for evidence based diagnosis and therapy monitoring. It provides biomarkers that offer fingerprints of neurological disorders even in cases where a lesion is not yet observed in MR images. The collection of molecules used as cerebral biomarkers that are detectable by (1)H NMR spectroscopy define the so-called "neurochemical profile". The non-invasive quality of this technique makes it suitable not only for diagnostic purposes but also for therapy monitoring paralleling an eventual neuroprotection. The application of (1)H NMR spectroscopy in basic and translational neuroscience research is discussed here.

Cohort profile: the Swiss HIV Cohort study.

The substantial recurrence rate of colorectal cancer following potentially curative resection has fuelled the search for effective adjuvant therapy. Previous trials using 5-fluorouracil (5-FU) as a single agent or in combination chemotherapy regimens have not demonstrated meaningful benefits, an impression reflected in the results of a meta-analysis encompassing large patient numbers. Newer developments utilizing intraportal chemotherapy and the combination of 5-FU and levamisole have resulted in lower recurrence rates and improved survival in patients with colon cancer. In advanced disease, the biochemical modulation of 5-FU by Leucovorin has been shown to prolong survival in some studies. Combined chemotherapy and radiotherapy or chemotherapy alone have showed promising results in rectal cancer. These developments have now been incorporated into ongoing trials.

A microRNA profile of human CD8.

BackgroundRecently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8+CD25+ Treg cells and the impact of microRNAs on molecules associated with immune regulation.MethodsWe purified human natural CD8+ Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions. Using TaqMan low-density arrays and microRNA qPCR for validation, we could identify a microRNA `signature¿ for CD8+CD25+FOXP3+CTLA-4+ natural Treg cells. We used the `TargetScan¿ and `miRBase¿ bioinformatics programs to identify potential target sites for these microRNAs in the 3¿-UTR of important Treg cell-associated genes.ResultsThe human CD8+CD25+ natural Treg cell microRNA signature includes 10 differentially expressed microRNAs. We demonstrated an impact of this signature on Treg cell biology by showing specific regulation of FOXP3, CTLA-4 and GARP gene expression by microRNA using site-directed mutagenesis and a dual-luciferase reporter assay. Furthermore, we used microRNA transduction experiments to demonstrate that these microRNAs impacted their target genes in human primary Treg cells ex vivo.ConclusionsWe are examining the biological relevance of this `signature¿ by studying its impact on other important Treg cell-associated genes. These efforts could result in a better understanding of the regulation of Treg cell function and might reveal new targets for immunotherapy in immune disorders and cancer.

Lapatax: Safety profile of neoadjuvant lapatinib combined with docetaxel in Her 2/neu overexpressing breast cancer - EORTC protocol 10054

Objective: To assess the safety/tolerability of the combination lapatinib (L) and docetaxel (D) in patients with Her 2/neu overexpressing breast cancer (BC). This study is important as it will define how to deliver lapatinib with taxotere, a highly active drug in breast cancer. Patients and Methods: Female patients (pts) with locally advanced, inflammatory or large operable BC were treated with escalating doses of L from 1000 to 1250 mg/day, in combination with D given IV every 21 days at doses ranging from 75 to 100 mg/m2 for 4 cycles. At least 3 pts were treated at each dose level. The definition of dose limiting toxicity (DLT) is based on the toxicity assessed at cycle 1 as follows: any grade 3−4 non hematological toxicity, ANC < 0.5 G/L lasting for 7 days or more, febrile neutropenia or thrombocytopenia <25 G/L. GCSF was not permitted as primary prophylaxis. Core biopsies were mandatory at baseline and after cycle 4. Pharmcokinetic (PK) samples were collected on day 1 of cycles 1 and 2. Results: To date, 18 pts with a median age of 53 years (range 36−65) have been enrolled at 5 Dose Levels (DLs). The toxicity profile for 18 patients (68 documented cycles) is summarized below. At DL5 (1000/100), 2 pts had DLTs (neutropenia grade 4 _7 days and febrile neutropenia), and 3 additional pts were enrolled with primary prophylactic G-CSF. As expected, the safety profile improved and the dose escalation will continue with prophylactic G-CSF to investigate DL6 (1250/100). These findings are consistent with published Phase I data for this combination [1]. N= 18 patients n (%) Grade 1 Grade 2 Grade 3 Grade 4 neutropenia 1 (6) 3 (17) 13 (72) febrile neutropenia 2 (11) fatigue 8 (44) 7 (39) diarrhoea 9 (50) 3 (17) pain: joint/muscle/other 5 (28)/4 (22)/3 (17) 4 (22)/4 (22)/3 (17) 0/0/1 (6) constipation 2 (11) 3 (17) 1 (6) elevated transaminases SGPT/SGOT 7 (39)/5 (28) Conclusions: The main toxicity of the L + D combination is haematological and was reached at DL5 (1000/100), without primary GCSF. An additional DL6 with primary prophylactic GCSF is being investigated (1250/100). PK data will be presented at the meeting plus the recommended dose for phase II studies.

Accuracy profile validation of a new analytical method for propane measurement using headspace-gas chromatography-mass spectrometry

Propane can be responsible for several types of lethal intoxication and explosions. Quantifying it would be very helpful to determine in some cases the cause of death. Some gas chromatography-mass spectrometry (GC-MS) methods of propane measurements do already exist. The main drawback of these GC-MS methods described in the literature is the absence of a specific propane internal standard necessary for accurate quantitative analysis. The main outcome of the following study was to provide an innovative Headspace-GC-MS method (HS-GC-MS) applicable to the routine determination of propane concentration in forensic toxicology laboratories. To date, no stable isotope of propane is commercially available. The development of an in situ generation of standards is thus presented. An internal-labeled standard gas (C3DH7) is generated in situ by the stoichiometric formation of propane by the reaction of deuterated water (D2O) with Grignard reagent propylmagnesium chloride (C3H7MgCl). The method aims to use this internal standard to quantify propane concentrations and, therefore, to obtain precise measurements. Consequently, a complete validation with an accuracy profile according to two different guidelines, the French Society of Pharmaceutical Sciences and Techniques (SFSTP) and the Gesellschaft für toxikologische und Forensische Chemie (GTFCh), is presented.

Distribution profile of zwitterions and hydrolysis of esters derived from N-benzylpiperazine

Résumé Les esters sont des agents thérapeutiques largement utilisés comme médicaments et prodrogues. Leurs dégradation est chimique et enzymatique. Le Chapitre IV de cette thèse a comme objet l'hydrolyse chimique de plusieurs dérivés esters du 2,3-dimethoxyphenol. Des composés modèles ont été synthétisés dans le but de déterminer leur mécanismes de dégradation. Les profils d'ionisation et d'hydrolyse de ces composés ont permis d'identifier la présence d'une catalyse intramoléculaire basique par un atome d'azote non-protoné. Les effets électroniques exercés par les groupes phenylethenyle et phenylcyclopropyle influencent également la vitesse d'hydrolyse des esters. La résolution des problèmes liés à l'adsorption et la perméation est devenue à nos jours l'étape limitante dans la conception de nouveaux médicaments car de trop nombreux candidats prometteurs ont échoué à cause d'une mauvaise biodisponibilité. La lipophilie décrit le partage d'un médicament entre une membrane lipidique et son environnement physiologique aqueux, et de ce fait elle influence sa pharmacocinétique. Des études récents ont mis en évidence l'importance de la détermination de la lipophilie des espèces ionisées vu leur considérable impact biologique. Le Chapitre V de cette thèse est centré sur une classe particulière de composés ionisables, les zwitterions. Plusieurs methoxybenzylpiperazines de nature zwitterionique ont été étudiées. Leurs profils d'ionisation ont montré que dans un large intervalle de pH, l'espèce prédominante est le zwitterion. Les profils de lipophilie ont montré que leur lipophilie est plus élevée que celles des zwitterions courants. Une interaction électrostatique entre l'oxygène du carboxylate et l'azote protoné est responsable de ce profil et rend la plupart des zwitterions non-donneurs de liaison hydrogène. Ces deux aspects peuvent favoriser le passage de la barrière hémato-éncephalique. Les données biologiques ont par la suite confirmé cette hypothèse pour un certain nombre de composés. Résumé large public Les esters sont des composés souvent rencontrés en chimie thérapeutique. Ils sont dégradés en milieu aqueux par une réaction d'hydrolyse, avec ou sans la participation d'enzymes. Dans ce travail de thèse, une série d'esters ont été étudiés dans le but d'établir une relation entre leur structure et les mécanismes responsables de leur dégradation chimique. Il a été prouvé que la dégradation est accélérée par un atome d'azote non-protoné. D'autres mécanismes peuvent intervenir en fonction du pH du milieu. La présence d'une liaison simple ou double ou d'un groupe phenylcyclopropyle peut également influencer la vitesse de dégradation. Il est essentiel, dans la conception de nouveaux médicaments, d'optimiser les étapes qui influencent leur distribution dans le corps. Ce dernier peut être visualisé comme une série infinie de compartiments aqueux séparés par des membranes lipidiques. La lipophilie est une propriété moléculaire importante qui décrit le passage des barrières rencontrées par les médicaments. Des études récentes ont mis en évidence l'importance de déterminer la lipophilie des espèces ionisées vu leur considérable impact biologique. Dans ce travail de thèse a été étudiée une série particulière de composés ionisables , les zwitterions. Une relation a été établie entre leur structure et leur proprietés physico-chimiques. Une lipophilie plus élevée par rapport à celle des zwitterions courants a été trouvée. Une interaction entre les groupes chargés des zwitterions étudiés est responsable de ce comportement inattendu et rend la plupart d'entre eux non-donneurs de liaison hydrogène. Ces deux facteurs peuvent favoriser la pénétration cérébrale. Les données biologiques ont confirmé cette hypothèse pour un certain nombre de composés. Summary Esters are often encountered in medicinal chemistry. Their hydrolysis may be chemical as well as enzymatic. Chapter IV of this manuscript provides a mechanistic insight into the chemical hydrolysis of a particular series of basic esters derived from 2,3-dimethoxyphenol. Their ionization and pH-rate profiles allowed to identify the presence of an intramolecular base catalysis by a non-protonated nitrogen atom. Electronic effects exerted by the phenylethenyl and phenylcyclopropyl groups that are present in the structure of the esters also influenced their rate of hydrolysis. Numerous works in the literature witness of the importance of lipophilicity in determining the fate of a drug. Most published partition coefficients are those of neutral species. In contrast, no exhaustive treatment of the lipophilicity of charged molecules is available at present, and a lack of information characterizes in particular zwitterions. Chapter V of this manuscript provides an insight into the physicochemical parameters of a series of zwitterionic methoxybenzylpiperazines. Their ionization profiles showed that they exist predominantly in the zwitterionic form in a broad pH-range. An electrostatic interaction between the oxygen of the carboxylate and the protonated nitrogen atom is increases the lipophilicity of the investigated zwitterions, and prevents the majority of them to express their hydrogen-bonding capacity. These two aspects may favor the crossing of the blood-brain barrier. The available ratios PSt/PSf measured in vitro have confirmed this point for a number of compounds.