Determination of the standard deviation for proficiency assessment from past participant’s performances

The “uncertainty function” introduced by Thompson et al. estimates the reproducibility standard deviation (SR) as a function of concentration. This model was successfully applied to a data set derived from three proficiency testing schemes aiming at the quantification of three toxic elements (cadmium, lead and mercury) in blood and urine. A threshold concentration was determined for each element. Below this concentration SR is found to be constant, while above it the reproducibility relative standard deviation is constant. This model allows the a priori estimation of standard deviation for performance assessment for proficiency testing rounds.JRC.D.5-Standards for Food Bioscienc

Determination of the standard deviation for proficiency assessment from past participant's performances

The "uncertainty function" introduced by Thompson et al. estimates the reproducibility standard deviation as a function of concentration or mass fraction. This model was successfully applied to data derived from three proficiency testing schemes aiming at the quantification of cadmium, lead and mercury in blood and urine. This model allows the estimation of standard deviation for the performance assessment for proficiency testing rounds

Facteurs pronostiques à la psychothérapie chez les troubles de la personnalité : implication de questionnaires autorapportés

Objectif Les taux d’abandon en psychothérapie sont reconnus comme étant élevés chez les patients/patientes souffrant de troubles de la personnalité (TP ; variant entre 25 % et 64 % pour le trouble de personnalité limite). Devant ce constat, la Grille de facteurs pronostiques à la psychothérapie (GFPP ; Gamache et coll., 2017) a été développée afin d’identifier précisément les patients/patientes souffrant de TP à haut risque d’abandonner la thérapie à partir de 15 critères, regroupés en 5 facteurs : Narcissisme pathologique, Antisocialité/Psychopathie, Gains secondaires, Faible motivation, Traits du groupe A. Par ailleurs, nous en connaissons relativement peu sur la pertinence des questionnaires autorapportés couramment utilisés auprès de la clientèle dans l’établissement du pronostic de traitement. Ainsi, le but de l’étude est d’évaluer les liens entre de tels questionnaires et les 5 facteurs de la GFPP.Méthode Un échantillon de 174 personnes avec un TP (dont 56 % avec traits ou TP limite), évaluées au Centre de traitement Le Faubourg Saint-Jean, ont rempli les versions françaises des questionnaires suivants : Borderline Symptom List (BSL-23), Brief Version of the Pathological Narcissism Inventory (B-PNI), Interpersonal Reactivity Index (IRI), Buss-Perry Aggression Questionnaire (BPAQ), Barratt Impulsiveness Scale (BIS-11), Questionnaire de fonctionnement social (QFS), Self and Interpersonal Functioning Scale (SIFS) et Personality Inventory for DSM-5- Faceted Brief Form (PID-5-FBF). La GFPP a été cotée par une équipe de psychologues expérimentés dans le traitement des TP. Des analyses descriptives et de régression entre les questionnaires autorapportés et les 5 facteurs de la GFPP de même que son score total ont été réalisées. Le but de ces analyses est de déterminer quelles variables des questionnaires autorapportés remplis par les personnes référées pour un TP, et principalement un TPL, contribuent le plus fortement à la prédiction statistique des variables de la GFPP cotée par les cliniciens.Résultats Les sous-échelles qui contribuent significativement au score du facteur Narcissisme pathologique (R2 ajusté = 0,12) sont : Empathie (SIFS), Impulsivité (inversement ; PID-5) et Rage revendicatrice (B-PNI). Les sous-échelles associées au facteur Antisocialité/Psychopathie (R2 ajusté = 0,24) sont Manipulation, Soumission (inversement) et Dureté du PID-5 ainsi que l’échelle Souci empathique de l’IRI. Les échelles contribuant substantiellement au facteur Gains secondaires (R2 ajusté = 0,20) sont Fréquence (QFS), Colère (inversement ; BPAQ), Fantaisie (inversement) et Souci empathique (IRI), Perfectionnisme rigide (inversement) et Croyances inhabituelles (PID-5). Le facteur Faible motivation (R2 ajusté = 0,10) est expliqué significativement par le score total au BSL (inversement) et la sous-échelle Satisfaction (QFS). Finalement, les sous-échelles significativement associées au facteur Traits du groupe A (R2 ajusté = 0,09) sont Intimité (SIFS) et Soumission (inversement ; PID-5).Conclusion : Certaines échelles des instruments autorapportés montrent des associations modestes, mais significatives avec les résultats obtenus aux facteurs de la GFPP. Ces échelles pourraient donc s’avérer utiles dans la cotation de la GFPP et fournir des informations complémentaires pour l’orientation clinique.Objectives Dropout rates in psychotherapy are known to be high in patients with personality disorders (PD; ranging from 25% and 64% for Borderline PD). Faced with this observation, the Treatment Attrition-Retention Scale for Personality Disorders (TARS-PD; Gamache et coll., 2017) was developed to precisely identify patients with PD at high risk of abandoning therapy based on 15 criteria, regrouped in 5 factors: Pathological Narcissism, Antisocial/Psychopathy, Secondary Gain, Low Motivation, and Cluster A Features. However, we have limited knowledge about the relevance of self-reported questionnaires commonly used with PD patients to establish treatment prognosis. Thus, the purpose of this study is to evaluate the link between such questionnaires and the five factors of the TARS-PD.Method Data was retrospectively retrieved from the clinical files of 174 participants with a PD (including 56% with borderline traits or PD), who were evaluated at the Centre de traitement le Faubourg Saint-Jean and completed the French version of the following questionnaires: Borderline Symptom List (BSL-23), Brief Version of the Pathological Narcissism Inventory (B-PNI), Interpersonal Reactivity Index (IRI), Buss-Perry Aggression Questionnaire (BPAQ), Barratt Impulsiveness Scale (BIS-11), Social Functioning Questionnaire (SFQ), Self and Interpersonal Functioning Scale (SIFS) and Personality Inventory for DSM-5- Faceted Brief Form (PID-5-FBF). The TARS-PD was completed by well-trained psychologists specialized in PD treatment. Descriptive analyses and regression between self-reported questionnaires and the five factors of the TARS-PD as well as its total score were performed to determine which variables from the self-reported questionnaires completed by the individuals contribute most strongly to the statistical prediction of the variables of the TARS-PD rated by the clinicians.Results The subscales that significantly contribute to the Pathological Narcissism factor (adjusted R2=0,12) are: Empathy (SIFS), Impulsivity (negatively; PID-5), and Entitlement Rage (B-PNI). The subscales associated with the Antisociality/Psychopathy factor (adjusted R2=0,24) are Manipulativeness, Submissiveness (negatively), and Callousness from the PID-5, and Empathic Concern (IRI). The scales contributing substantially to the Secondary gains factor (adjusted R2=0,20) are Frequency (SFQ), Anger (negatively; BPAQ), Fantasy (negatively) and Empathic Concern (IRI), Rigid Perfectionism (negatively) and Unusual Beliefs and Experiences (PID-5). Low motivation (adjusted R2=0,10) is significantly explained by Total BSL score (negatively) and Satisfaction (SFQ) subscale. Finally, the subscales significantly associated to Cluster A features (adjusted R2=0,09) are Intimacy (SIFS) and Submissiveness (negatively, PID-5).Conclusion Some scales from self-reported questionnaires demonstrated modest but significant associations with TARS-PD factors. Those scales might be useful in the scoring of the TARS-PD and provide additional information for patients’ clinical orientation

PACE4 cleaves PRR intracellularly in prostate cancer cells.

(A) Western blot analysis showing Prorenin Receptor (PRR), furin, and PACE4 expression, sPRR secretion, and cell lysate and conditioned media total lane protein (CLTLP, CMTLP) in LNCaP cells infected with a control non-target shRNA (NT), Furin shRNA (shfurin), or PACE4 shRNA (shPACE4). (B) Western Blot analysis demonstrating the expression of PRR and secretion of sPRR in LNCaP cells infected with an empty pLenti6 vector or with pLenti6-PACE4 to overexpress PACE4. (C) Quantification of sPRR levels in pLenti6 and pLenti-PACE4-infected LNCaP cells (*PD) Western blot showing the reduction in PRR processing resembled as a ratio of HA-tagged M8.9 (M8.9-HA) to HA-tagged full-length PRR (PRR-HA) in cellular extract of LNCaP cells after a 50 μM PACE4 inhibitor [33] LLLRVK-amidinobenzylamide (Amba) (C23) treatment. (E) Corresponding quantification of the ratio of M8.9-HA to PRR-HA standardized over total lane protein (TLP) (*PF) Analysis of PRR peptide cleavage by recombinant PACE4 (rPACE4) or recombinant furin (rfurin) monitored after a 2-hour incubation by high pressure liquid chromatography (HPLC). Mass spectrometry was done to confirm identity of peptide after cleavage. Cleavage site is underlined on the peptide sequence. Western blot analysis of PRR expression and sPRR secretion and quantification of sPRR secretion after DMSO (Vehicle), 50 μM multi-Leucine peptide (ML) PACE4 inhibitor, or 50 μM PEGylated cell-impermeable ML (PEG8-ML) treatment of DU145 (***PG, H) or LNCaP (I, J) (**P<0.01, n = 3) cells, respectively. Beta-Actin (β-actin) and TLP were used as loading controls. Data are presented as the mean ± SEM. Statistical tests were conducted using Student’s t test.</p

Deletion of the gene encoding G0/G 1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice

AIMS/HYPOTHESIS: Obesity is a global epidemic resulting from increased energy intake, which alters energy homeostasis and results in an imbalance in fat storage and breakdown. G0/G1 switch gene 2 (G0s2) has been recently characterised in vitro as an inhibitor of adipose triglyceride lipase (ATGL), the rate-limiting step in fat catabolism. In the current study we aim to functionally characterise G0s2 within the physiological context of a mouse model. METHODS: We generated a mouse model in which G0s2 was deleted. The homozygous G0s2 knockout (G0s2 (-/-)) mice were studied over a period of 22 weeks. Metabolic variables were measured including body weight and body composition, food intake, glucose and insulin tolerance tests, energy metabolism and thermogenesis. RESULTS: We report that G0s2 inhibits ATGL and regulates lipolysis and energy metabolism in vivo. G0s2 (-/-) mice are lean, resistant to weight gain induced by a high-fat diet and are glucose tolerant and insulin sensitive. The white adipose tissue of G0s2 (-/-) mice has enhanced lipase activity and adipocytes showed enhanced stimulated lipolysis. Energy metabolism in the G0s2 (-/-) mice is shifted towards enhanced lipid metabolism and increased thermogenesis. G0s2 (-/-) mice showed enhanced cold tolerance and increased expression of thermoregulatory and oxidation genes within white adipose tissue, suggesting enhanced \u27browning\u27 of the white adipose tissue. CONCLUSIONS/INTERPRETATION: Our data show that G0s2 is a physiological regulator of adiposity and energy metabolism and is a potential target in the treatment of obesity and insulin resistance

PACE4 inhibition, like PRR knockdown, reduces V-ATPase activity.

(A) Representative proliferation images of LNCaP exposed to both DMSO or a 100 μM of PACE4 inhibitor [33] LLLRVK-amidinobenzylamide (Amba) (C23) over 0 and 64 hours. (B) Western blot analysis of soluble prorenin receptor (sPRR) secretion in conditioned media of LNCaP exposed to DMSO or a 100 μM C23. (C) Representative LysoTracker images of LNCaP cells transfected with non-silencing control siRNA (NSC), PRR siRNA 1 and 2, PACE siRNA, or treated with 100 nM Bafilomycin A1. (D) Quantification of LysoTracker signal intensity relative to number of cells in brightfield images treated with 1% DMSO (Vehicle), 50 μM C23, 100 nM Bafilomycin A1 (BafA1), or transfected with PRR siPRR 1 or siPRR 2. (E) Schematic showing the PRR-HA, sPRR-HA, and M8.9-HA vectors used in panels F, G and H. (F) Representative LysoTracker images of LNCaP cells transfected with empty vector (EV) and treated with DMSO, treated with 100 μM C23, transfected with PRR-HA and treated with 100 μM C23, transfected with M8.9-HA and treated with 100 μM C23, transfected with sPRR-HA and treated with 100 μM C23, or treated with 100 nM BafA1. (G) Corresponding quantification of LysoTracker intensity relative to cell number in the same treatments (**P ≤ 0.01, ***P ≤ 0.001, **** P H) Western blot analysis of PRR and HA expression in the same treatments. Total lane protein (TLP) was used as loading control. Data are presented as the mean ±SEM. Statistical tests were conducted using Student’s t test. Scale bar measures 100.</p

PTEN controls PACE4 expression and sPRR secretion in human prostate cancer cells, and both PACE4 and PRR expressions increase in human prostate tumor tissue.

(A) Western blot analysis showing less PACE4 endogenous protein expression after adenoviral Phosphatase and tensin homolog (PTEN) infection (PTEN-Ad) in PC3 and LNCaP cells. The same cells also exhibited less Prorenin Receptor (PRR) processing and less soluble Prorenin Receptor (sPRR) secretion in conditioned media (CM). Total lane protein (TLP) was used as a loading control. Quantification of (B) PACE4 expression and (C) sPRR secretion relative to the corresponding TLP in PC3 and LNCaP prostate cancer cells (*P D) Representative IHC tissue microarray images of PTEN, PACE4, and PRR staining on prostatic intraepithelial neoplasia (PIN) tissue and tumor tissue. Scale bar measures 100 μm. Dot plots representing the mean of the qualitative score assigned to (E) PTEN, (F) PACE4, and (G) PRR staining on PIN (n = 68) and tumor (n = 105) patient tissue microarrays (*PH) The Cancer Genome Atlas (TCGA) mRNA expression data in Log2 scale of PTEN, PCSK6 (PACE4), and ATP6AP2 (PRR) in tumor (T) and normal (N) prostate tissue.</p