Self-Contempt, the Working Alliance and Outcome in Treatments for Borderline Personality Disorder: An Exploratory Study.

Objective. We examined the role of expressed self-contempt in therapy for borderline personality disorder (BPD). Based on previous literature on BPD, we assumed an association between the self-contempt and the core symptoms of BPD. We also studied the progression of expressed self-contempt during the treatment and its effect on the alliance and the outcomes of treatment.Method. We rated the expressed self-contempt in 148 tape-recorded sessions with patients with BPD (N = 50), during a brief psychiatric treatment. We rated self-contempt at three time-points, using an observer-rate scale. Self-reported questionnaires were used to assess symptoms and the working alliance.Results. There are some associations between self-contempt and BPD symptoms. Expressed self-contempt did not change during the treatment. One measure of self-contempt was associated with a weaker alliance rated by the patients and with a stronger alliance rated by the therapists. The expression of high self-contempt was not predictive of outcomes when the initial level of problems was controlled for.Conclusions. The results highlight the importance to examine the complex effects of self-contempt in BPD undergoing treatment in a differentiated manner and suggest to clinicians and researchers to be attentive to this specific emotional state, and change therein, in psychotherapy.Keywords: Self-contempt; Borderline Personality Disorder; Brief Treatment; Therapeutic Alliance; EmotionTrial registration: ClinicalTrials.gov identifier: NCT01896024

Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice

Tuberculosis, caused by infection with Mycobacterium tuberculosis (Mtb), kills over 1.6 million people each year despite availability of antibiotics. The increase in drug resistant Mtb strains is a major public health emergency and host-directed therapy as adjunct to antibiotic treatment has gained increased interest. Cyclooxygenase inhibitors (COXi) are frequently used drugs to alleviate tuberculosis related symptoms. Mouse studies of acute intravenous Mtb infection have suggested a potential benefit of COXi for host-directed therapy. Here we show that COXi treatment (ibuprofen and celecoxib) is detrimental to Mtb control in different mouse models of respiratory infection. This effect links to impairments of the Type-1 helper (Th1) T-cell response as CD4 T-cells in COXi-treated animals have significantly decreased Th1 differentiation, reduced IFNγ expression and decreased protective capacity upon adoptive transfer. If confirmed in clinical trials, these findings could have major impact on global health and question the use of COXi for host-directed therapy.publishedVersio

Cell Type–Specific Transcriptome Analysis Reveals a Major Role for Zeb1 and miR-200b in Mouse Inner Ear Morphogenesis

Cellular heterogeneity hinders the extraction of functionally significant results and inference of regulatory networks from wide-scale expression profiles of complex mammalian organs. The mammalian inner ear consists of the auditory and vestibular systems that are each composed of hair cells, supporting cells, neurons, mesenchymal cells, other epithelial cells, and blood vessels. We developed a novel protocol to sort auditory and vestibular tissues of newborn mouse inner ears into their major cellular components. Transcriptome profiling of the sorted cells identified cell type–specific expression clusters. Computational analysis detected transcription factors and microRNAs that play key roles in determining cell identity in the inner ear. Specifically, our analysis revealed the role of the Zeb1/miR-200b pathway in establishing epithelial and mesenchymal identity in the inner ear. Furthermore, we detected a misregulation of the ZEB1 pathway in the inner ear of Twirler mice, which manifest, among other phenotypes, malformations of the auditory and vestibular labyrinth. The association of misregulation of the ZEB1/miR-200b pathway with auditory and vestibular defects in the Twirler mutant mice uncovers a novel mechanism underlying deafness and balance disorders. Our approach can be employed to decipher additional complex regulatory networks underlying other hearing and balance mouse mutants

High-Ability Influencers? The Heterogeneous Effects of Gifted Classmates

This paper examines how exposure to students identified as gifted (IQ≥130) affects achievement in secondary school and enrollment in post-compulsory education. By using unique student-level administrative data on achievement combined with psychological examination records, we are able to study the causal impact of gifted students on their classmates in unprecedented detail. We find a positive and significant effect of the exposure to gifted students on school achievement in both math and language. The impact of gifted students is, however, highly heterogeneous along three dimensions. First, we observe the strongest effects among male students and high achievers. Second, we show that male students benefit from the presence of gifted peers in all subjects regardless of their gender, whereas female students seem to benefit exclusively from the presence of female gifted students. Third, we find that gifted students diagnosed with emotional or behavioral disorders have zero-to-negative effects on their classmates' performance, a detrimental effect more pronounced for female students. After compulsory schooling, the results show that exposure to gifted classmates increases the likelihood of choosing a selective academic track. This effect, however, is entirely driven by male students

Perméabilité à la lumière de poches de protection des médicaments injectables: détermination par trois méthodes

Le pharmacien clinicien rattaché à un service de pharmacie clinique ambulatoire, qui se rend chez un patient pour lui dispenser un médicament et assurer un suivi thérapeutique, doit être en mesure de certifier que le médicament n'a pas été altéré par des facteurs externes tels que la chaleur, l'humidité, le gaz ou encore le rayonnement lumineux. Trois méthodes simples, permettant l'évaluation de la perméabilité à Ia lumière des poches utilisées pour le transport ont été mises au point et étudiées. La première utilise le principe de la photographie afin de comparer de manière qualitative Ia protection offerte par les différents types de poches. Les deux autres utilisent Ia spectrophotométrie comme moyen d'analyse; l'une étudie la perméabilité de la poche elle -même et l'autre permet de suivre Ia cinétique de dégradation de substances photosensibles. Dans cette étude, Ia vitamine K1, le chlorhydrate de chlorpromozine et la nifédipine ont été utilisés. Ces trois méthodes sont complémentaires et très simples à utiliser, elles permettent une analyse rapide de Ia perméabilité des poches nécessaire au pharmacien clinicien ambulatoire.By going to the patient to dispense drugs and provide a therapeutic monitoring, the home care service clinical pharmacist must be able to certify that medications do not undergo degradation by heat, humidity, gas or light. ln this study, three simple evaluation methods for the light permeability of plastic bags have been investigated. The first method is based on the photography principle. It enables a qualitative comparison of the protection provided by different plastic materials. The second method consists of studying the permeability of plastic bags directly in a spectrophotometer. Finally, the degradation of photosensitive substances introduced into the plastic bags can also be monitored by spectroscopic measurements. ln this case, the substances used were vitamin K1, chlorpromazine hydrochloride and nifedipin. These three methods are complementary and require a simple set-up. They enable a quick analysis of plastic bags permeability to light, which is very useful for a home care service clinical pharmacist

Semisynthetic biosensors for mapping cellular concentrations of nicotinamide adenine dinucleotides

We introduce a new class of semisynthetic fluorescent biosensors for the quantification of free nicotinamide adenine dinucleotide (NAD+) and ratios of reduced to oxidized nicotinamide adenine dinucleotide phosphate (NADPH/NADP+) in live cells. Sensing is based on controlling the spatial proximity of two synthetic fluorophores by binding of NAD(P) to the protein component of the sensor. The sensors possess a large dynamic range, can be excited at long wavelengths, are pH-insensitive, have tunable response range and can be localized in different organelles. Ratios of free NADPH/NADP+ are found to be higher in mitochondria compared to those found in the nucleus and the cytosol. By recording free NADPH/NADP+ ratios in response to changes in environmental conditions, we observe how cells can react to such changes by adapting metabolic fluxes. Finally, we demonstrate how a comparison of the effect of drugs on cellular NAD(P) levels can be used to probe mechanisms of action

Sodium sensing in neurons with a dendrimer-based nanoprobe.

Ion imaging is a powerful methodology to assess fundamental biological processes in live cells. The limited efficiency of some ion-sensing probes and their fast leakage from cells are important restrictions to this approach. In this study, we present a novel strategy based on the use of dendrimer nanoparticles to obtain better intracellular retention of fluorescent probes and perform prolonged fluorescence imaging of intracellular ion dynamics. A new sodium-sensitive nanoprobe was generated by encapsulating a sodium dye in a PAMAM dendrimer nanocontainer. This nanoprobe is very stable and has high sodium sensitivity and selectivity. When loaded in neurons in live brain tissue, it homogenously fills the entire cell volume, including small processes, and stays for long durations, with no detectable alterations of cell functional properties. We demonstrate the suitability of this new sodium nanosensor for monitoring physiological sodium responses such as those occurring during neuronal activity