Mentalization-based treatment for borderline personality disorder in adults and adolescents: For whom, when, and how?

Borderline personality disorder (BPD) is common in clinical practice. Psychotherapy is the treatment of choice, and Mentalization-based treatment (MBT) is one of the empirically supported treatments that are currently available. For adults, two variants of MBT (MBT day hospital (MBT-DH) and MBT intensive outpatient (MBT-IOP)) have been developed and empirically evaluated. In this paper, we will present a review of research of development, efficacy, and implementation of MBT. We first discuss evidence on the effectiveness of MBT-DH and MBT-IOP, the lack of comparative research, as well as the lack of research on predictors of treatment response. Next, we go on to discuss research suggesting that the dissemination and implementation of MBT for adolescents is hindered by the reluctance of clinicians to diagnose BPD in adolescence. As a result, there is a dearth of evidence-based treatments for adolescents, including MBT, although the recent increase in studies in this area suggests that this trend may be changing. Finally, we focus on the implementation of treatment programs for BPD patients. Although we now have different effective treatments for BPD, the implementation of these treatments in routine clinical practice has proven to be much more complex than initially thought. In addition, treatments such as MBT are multimodal, long-term treatments. Both societal pressures to increase the cost-effectiveness of our treatments, and new theoretical insights into the role of social learning and salutogenesis in the development of BPD, force us to reconsider some of our assumptions concerning the nature of treatment for individuals with BPD

Subtypes of borderline personality disorder patients: a cluster-analytic approach.

BACKGROUND: The borderline personality disorder (BPD) population is notably heterogeneous, and this has potentially important implications for intervention. Identifying distinct subtypes of patients may represent a first step in identifying which treatments work best for which individuals. METHODS: A cluster-analysis on dimensional personality disorder (PD) features, as assessed with the SCID-II, was performed on a sample of carefully screened BPD patients (N = 187) referred for mentalization-based treatment. The optimal cluster solution was determined using multiple indices of fit. The validity of the clusters was explored by investigating their relationship with borderline pathology, symptom severity, interpersonal problems, quality of life, personality functioning, attachment, and trauma history, in addition to demographic and clinical features. RESULTS: A three-cluster solution was retained, which identified three clusters of BPD patients with distinct profiles. The largest cluster (n = 145) consisted of patients characterized by "core BPD" features, without marked elevations on other PD dimensions. A second "Extravert/externalizing" cluster of patients (n = 27) was characterized by high levels of histrionic, narcissistic, and antisocial features. A third, smaller "Schizotypal/paranoid" cluster (n = 15) consisted of patients with marked schizotypal and paranoid features. Patients in these clusters showed theoretically meaningful differences in terms of demographic and clinical features. CONCLUSIONS: Three meaningful subtypes of BPD patients were identified with distinct profiles. Differences were small, even when controlling for severity of PD pathology, suggesting a strong common factor underlying BPD. These results may represent a stepping stone toward research with larger samples aimed at replicating the findings and investigating differential trajectories of change, treatment outcomes, and treatment approaches for these subtypes. TRIAL REGISTRATION: The study was retrospectively registered 16 April 2010 in the Nederlands Trial Register, no. NTR2292

Modulation of the <i>Neisseria gonorrhoeae </i>drug efflux conduit MtrE

We acknowledge funding through the Wellcome Trust Interdisciplinary Research Funds (grant WT097818MF), the Scottish Universities’ Physics Alliance (SUPA), Tenovus Tayside (grant T16/30) and the Tayside Charitable Trust. O.N.V. has been funded through a BBSRC CASE award (BB/J013072/1).Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. In Neisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings and in silico techniques. Our in vitro results show that MtrE can be regulated by periplasmic binding events and that the interaction between MtrE and MtrC is sufficient to stabilize this complex in an open state. In contrast to other efflux conduits, the open complex only displays a slight preference for cations. The maximum conductance we obtain in the in vitro recordings is comparable to that seen in our computational electrophysiology simulations conducted on the MtrE crystal structure, indicating that this state may reflect a physiologically relevant open conformation of MtrE. Our results suggest that the MtrC/E binding interface is an important modulator of MtrE function, which could potentially be targeted by new efflux inhibitors.Publisher PDFPeer reviewe

Enhanced and effective conformational sampling of protein molecular systems for their free energy landscapes

Protein folding and protein–ligand docking have long persisted as important subjects in biophysics. Using multicanonical molecular dynamics (McMD) simulations with realistic expressions, i.e., all-atom protein models and an explicit solvent, free-energy landscapes have been computed for several systems, such as the folding of peptides/proteins composed of a few amino acids up to nearly 60 amino-acid residues, protein–ligand interactions, and coupled folding and binding of intrinsically disordered proteins. Recent progress in conformational sampling and its applications to biophysical systems are reviewed in this report, including descriptions of several outstanding studies. In addition, an algorithm and detailed procedures used for multicanonical sampling are presented along with the methodology of adaptive umbrella sampling. Both methods control the simulation so that low-probability regions along a reaction coordinate are sampled frequently. The reaction coordinate is the potential energy for multicanonical sampling and is a structural identifier for adaptive umbrella sampling. One might imagine that this probability control invariably enhances conformational transitions among distinct stable states, but this study examines the enhanced conformational sampling of a simple system and shows that reasonably well-controlled sampling slows the transitions. This slowing is induced by a rapid change of entropy along the reaction coordinate. We then provide a recipe to speed up the sampling by loosening the rapid change of entropy. Finally, we report all-atom McMD simulation results of various biophysical systems in an explicit solvent

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10^{-8}; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10^{−10}; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)