pinecone/core-2020-05-10-deduplication huggingface dataset:
Exploring the paths between dysfunctional attitudes towards motherhood and postpartum depressive symptoms: The moderating role of self-compassion.

Better understanding how cognitive processes operate to influence women’s depressive
symptoms during the postpartum period is crucial for informing preventive and
treatment approaches. The present study aimed to examine the relationship between
women’s dysfunctional attitudes towards motherhood and depressive symptoms,
considering the mediating role of negative automatic thoughts and the moderating role
of self-compassion. A sample of 387 women in the postpartum period cross-sectionally
answered a set of questionnaires to assess dysfunctional attitudes towards motherhood,
negative automatic thoughts (general and postpartum-specific), depressive symptoms
and self-compassion. Women with clinically significant depressive symptoms presented
more dysfunctional attitudes towards motherhood, more frequent negative thoughts and
lower self-compassion. More dysfunctional beliefs about others’ judgments and about
maternal responsibility were associated with higher depressive symptoms, and this
effect occurred through both general and postpartum-specific thoughts related to the
metacognitive appraisal of the thought content. Moreover, these relationships occurred
only when women presented low or moderate levels of self-compassion. These results
highlight the need to comprehensively assess women’s cognitive variables during the
postpartum period with appropriate measures, for the early identification of women with
more dysfunctional beliefs about motherhood, who may be at higher risk of depression.
Moreover, preventive/treatment approaches should aim not only to challenge women’s
pre-existing dysfunctional beliefs but also to promote a more self-compassionate
attitude towards themselves
The impact of illness-related shame on psychological health and social relationships: Testing a mediational model in students with chronic illness

This study explores the impact of illness‐related shame on the quality of social relationships and
psychological health in chronic patients. We aimed to examine the roles of fear of receiving compassion
from others and experiential avoidance as potential mediators of this relationship.
Although some studies have demonstrated the negative impact of chronic illness‐related shame
on psychological functioning, the mechanisms that may underlie this link remain understudied.
The sample was comprised by 115 college students, which had been diagnosed with at least 1
chronic illness. Participants completed self‐report measures on an online platform. This study's
design was cross‐sectional. A path analysis was conducted using structural equation modelling.
Results showed that the impact of illness‐related shame on both psychological health (R2 = .45)
and the quality of social relationships (R2 = .33) was fully accounted by fear of compassion from
others and experiential avoidance. This model revealed an excellent fit. Fear of receiving compassion
from others was the main mediator of the illness‐related shame link with the quality of social
relationships (β = −.22). The main mediator of the association between shame‐related chronic
illness and psychological health was experiential avoidance (β = −.21).This study shed light on
possible psychological mechanisms linking feelings of shame associated with having a chronic
condition and impaired social relationships and mental health. On one hand, resisting feelings
of compassion and care from others and, on the other hand, avoiding difficult internal experiences
and situations that might trigger them seem to underlie the impact of shame on psychological and
social functioning in chronic patients
Operant procedures applied to a conversion disorder

Contains fulltext :
                  29789.pdf (publisher's version ) (Open Access)Conversion symptoms, as identified by the existing classification systems, do not form a single unitary class. It is therefore difficult to find an adequate treatment that closely connects to the basic characteristics of the disease. Instead, we designed a treatment method that closely relates to the behavioural aspects of a conversion disorder. We reasoned that motor patterns can be taught straightforwardly by means of operant conditioning methods and that movement disorders in conversion should be treated accordingly. Our case study shows that carefully retraining deficient motor patterns may constitute the core of the treatment for conversion disorders
Early change in defence mechanisms and coping in short-term dynamic psychotherapy: relations with symptoms and alliance.

Several patient-related variables have already been investigated as predictors of change in psychodynamic psychotherapy. Defensive functioning is one of them. However, few studies have investigated adaptational processes, encompassing defence mechanisms and coping, from an integrative or comparative viewpoint. This study includes 32 patients, mainly diagnosed with adjustment disorder and undergoing time-limited psychodynamic psychotherapy lasting up to 40 sessions, and will focus on early change in defence and coping. Observer-rater methodology was applied to the transcripts of two sessions of the first part of the psychotherapeutic process. It is assumed that the contextual-relational variable of therapeutic alliance intervenes as moderator on change in adaptational processes. Results corroborated the hypothesis, but only for coping, whereas for defences, overall functioning remained stable over the first 20 sessions of psychotherapy. These results are discussed within the framework of disentangling processes underlying adaptation, i.e., related to issues on trait and state aspects, as well as the role of the therapeutic alliance
Relationship between the Social Cognition and Object Relations Scale (SCORS) and attachment style in a clinical sample

This present study examined the relationship between the Social Cognition and Object Relations Scale (SCORS) and two measures of adult attachment: the Relationship Questionnaire (RQ) and the Experiences in Close Relationships Questionnaire‐Revised (ECR‐R). Forty‐five patients (76% female) at a university‐based outpatient treatment clinic participated in this study. We hypothesized that higher levels of attachment security would be associated with higher, more adaptive ratings on the SCORS variables. Results indicated that the SCORS Self‐Esteem (SE) variable was significantly positively related to the RQ's Secure Attachment ratings and negatively related with the ECR‐R's Anxious Attachment scale. Additionally, negative trends were noted between SE and the RQ's Fearful and Preoccupied Attachment scores. The SCORS Emotional Investments in Relationships and Affective Quality of Representations variables were associated with higher Secure scores and lower, more maladaptive Preoccupied scores on the RQ. It was also associated with greater attachment anxiety as measured by the ECR‐R. Using both clinician (SCORS) and participant‐rated measures (ECR‐R and RQ), this study provides further understanding on how object representations and attachment style relate within a clinical sample. Results are discussed in light of prior research examining relationships between object relations and adult attachments, and clinical implications are also reviewed. Copyright © 2010 John Wiley & Sons, Ltd.   Key Practitioner Message:   • Individuals with higher levels of attachment anxiety may enter therapy with more self‐image problems.  • Individuals with higher levels of attachment anxiety may enter therapy with more maladaptive expectations about relationships.  • Patients who endorse high levels of attachment anxiety (e.g., fearful and preoccupied) may be more likely to present with Axis II complaints.  • Examining a patient's attachment style and object relations using different measures of assessment (e.g., explicit and implicit) can help gain a deeper and more comprehensive understanding of a patient
'Neutralizing the Patient': Therapists' Accounts of Sexual Boundary Violations

Sexual contact between psychological therapists and their clients is regarded as highly damaging, both to the clients and to the professions, and regulatory bodies impose increasingly severe sanctions upon those practitioners who are disciplined. The present study captured therapists' accounts of sexual boundary violations through interpretative phenomenological analysis of interviews with three disciplined practitioners about their relationships with clients and former clients. The results highlighted two key themes relating to (i) therapists' efforts to neutralize the power imbalances between themselves and the clients by minimizing the clients' mental health problems, stressing the conventionality of the relationships and not testing the appropriateness of the relationship with their supervisors, and (ii) a shifting identity of the therapist between hero, victim, perpetrator, which permeated their accounts as the relationship moved from success to failure. In order for a sexual boundary violation to occur, the therapist needed to generate a sense of equivalent status between themselves and the client. As the relationships failed, the therapists' accounts of the clients shifted and the inequality of the relationship re-emerged. The results are discussed in terms of implicit theories and the implications for both training and supervision in the prevention of sexual boundary violations. Copyright © 2011 John Wiley & Sons, Ltd. Key Practitioner Message: In accounting for their sexual boundary violations, this small sample of therapists minimized the power imbalances between themselves and their clients. Minimizing the client's mental health problems; stressing the conventionality of the relationship; stressing the therapist's own needs-all contributed to the neutralization of the client's patient status. A relationship with a client that we are not willing to discuss with our supervisor should be a cause for concern. © 2011 John Wiley & Sons, Ltd
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org)
Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach

Myopathy is a group of muscle diseases that can be induced or exacerbated by drug-drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine-simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System
To address emerging infections, we must invest in enduring systems: The kinetics and dynamics of health systems strengthening

Clinical pharmacology uses foundational principles of pharmacokinetics (PK) and pharmacodynamics (PD) to address medication use spanning a continuum from molecules to the masses. In the realm of infectious diseases, PK/PD attributes are considered especially important, because subtherapeutic dosing of antibiotics has been associated with poorer clinical outcomes in patients and increased incidences of drug resistance in populations. In consideration of these PK/PD principles, we will describe the analogous relationship between health systems strengthening, including for educating healthcare providers about emerging infections, and the tenets of therapeutic drug monitoring
The next frontier: Fostering innovation by improving health data access and utilization

Beneath most lively policy debates sit dry-as-dust theoretical and methodological discussions. Current disputes over the EU Adaptive Pathways initiative and the proposed US 21st Century Cures Act may ultimately rest on addressing arcane issues of data curation, standardization, and utilization. Improved extraction of inform ation on the safety and effectiveness of drugs-in-use must parallel adjustments in evidence requirements at the time of licensing. To do otherwise may compromise safety and efﬁcacy in the name of fostering innovation
In vitro sensitivity to methyl-prednisolone is associated with clinical response in pediatric idiopathic nephrotic syndrome

The aim of this study was to evaluate the in vitro steroid sensitivity as a predictor of clinical response to glucocorticoids in childhood idiopathic nephrotic syndrome (INS). Seventy-four patients (median age 4.33, interquartile range [IQR] 2.82-7.23; 63.5% male) were enrolled in a prospective multicenter study: in vitro steroid inhibition of patients' peripheral blood mononuclear cell proliferation was evaluated by [methyl-(3) H] thymidine incorporation assay at disease onset (T0) and after 4 weeks (T4) of treatment. Steroid dependence was associated with increased in vitro sensitivity at T4 assessed both as drug concentration inducing 50% of inhibition (IC50 ; odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.24-0.85; P = 0.0094) and maximum inhibition at the highest drug concentration (Imax ; OR = 1.13, 95% CI = 1.02-1.31; P = 0.017). IC50 > 4.4 nM and Imax < 92% at T4 were good predictors for optimal clinical response. These results suggest that this test may be useful for predicting the response to glucocorticoid therapy in pediatric INS
Variants in pharmacokinetic transporters and glycemic response to metformin: A metgen meta-analysis

Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D
Regulatory consequences of “Brexit” for the development of medicinal products

The United Kingdom voted in a referendum in June 2016 to leave the European Union (EU) after 45 years of membership. Among the many political, social, and scientific consequences are those for the regulation of health care products. No longer will the efficacy, safety, and quality of medicines in the United Kingdom be subject to an EU regulatory framework. The European Medicines Agency (EMA), which is currently located in London, will move elsewhere in Europe. The pharmaceutical industry will reassess its commitment to the UK health scene
Drug repurposing by simulating flow through protein-protein interaction networks

As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining  simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and uses Support Vector Machine to identify potentially effective drugs in our model disease, psoriasis.  Using this method, we screened about 1500 marketed and investigational substances, identified fifty-one drugs that were potentially effective and selected three of them for experimental confirmation. All drugs inhibited TNF-induced NFkappaB activity in vitro, suggesting they might be effective for treating psoriasis in humans. Additionally, these drugs significantly inhibited imiquimod-induced ear thickening and inflammation in the mouse model of the disease. All results suggest high prediction performance for the algorithm. This  article is protected by copyright. All rights reserved
A population pharmacokinetic model incorporating saturable pharmacokinetics and autoinduction for high rifampicin doses

The research leading to these results has received funding from the Swedish Research Council in addition to the Innovative Medicines Initiative Joint Undertaking (www.imi.europe.eu) under grant agreement n°115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.Accumulating evidence suggest that increasing doses of rifampicin may shorten tuberculosis treatment. The PanACEA HIGHRIF1 trial assessed safety, pharmacokinetics and anti-mycobacterial activity of rifampicin at doses up to 40 mg/kg. Eighty-three pulmonary tuberculosis patients received 10, 20, 25, 30, 35 or 40 mg/kg rifampicin daily over 2 weeks, supplemented with standard doses of isoniazid, pyrazinamide and ethambutol in the second week. This study aimed at characterizing rifampicin pharmacokinetics observed in HIGHRIF1 using non-linear mixed effects modeling. The final population pharmacokinetic model included an enzyme turn-over model accounting for time-dependent elimination due to auto-induction, concentration-dependent clearance and dose-dependent bioavailability. The relationship between clearance and concentration was characterized by a Michaelis-Menten relationship. The relationship between bioavailability and dose was described using an Emax relationship. The model will be key in determining exposure-response relationships for rifampicin and should be considered when designing future trials and when treating future patients with high dose rifampicin.Publisher PDFPeer reviewe
Sulfasalazine‐induced agranulocytosis is associated with the human leukocyte antigen locus

Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine, which is used to treat inflammatory joint and bowel disease. We performed a genome‐wide association study comprising 9,380,034 polymorphisms and 180 HLA alleles in 36 cases of sulfasalazine‐induced agranulocytosis and 5,170 population controls. Sulfasalazine‐induced agranulocytosis was significantly associated with the HLA region on chromosome 6. The top hit (rs9266634) was located close to HLA‐B, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69) P = 2.55 × 10 −8). We HLA‐sequenced a second cohort consisting of 40 cases and 142 treated controls, and confirmed significant associations with HLA‐B*08:01, OR = 2.25 (95% CI (1.02, 4.97) P = 0.0439), in particular the HLA‐B*08:01 haplotype HLA‐DQB1*02:01‐DRB1*03:01‐B*08:01‐C*07:01, OR = 3.79 (95% CI (1.63, 8.80) P = 0.0019), and with HLA‐A*31:01, OR = 4.81 (95% CI (1.52, 15.26) P = 0.0077). The number needed to test for HLA‐B*08:01 and HLA‐A*31:01 to avoid one case was estimated to be 1,500. We suggest that intensified monitoring or alternative treatment should be considered for known carriers of HLA‐B*08:01 or HLA‐A*31:01
Key learning outcomes for clinical pharmacology and therapeutics education in Europe: a modified Delphi study

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of an uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe.  We used a modified Delphi method consisting of three  questionnaire rounds and a panel meeting. 129 experts from 27 European countries were asked to rate 307 learning outcomes. 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes  might be acquired
Circularly polarised luminescence from helically chiral “confused” N,N,O,C-Boron-Chelated Dipyrromethenes (BODIPYs).

Chiral organic fluorophores have significant promise in the development of efficient emitters of circularly polarized light. Herein we describe a helically chiral boron dipyrromethene (BODIPY) with a hitherto unreported N,N,O,C-boron-chelation motif, synthesised by means of a one-pot boron metathesis, nucleophilic aromatic substitution (SNAr), Suzuki coupling, boron chelation, cascade reaction. Resolution of the racemic BODIPY (by preparative HPLC on a chiral stationary phase) allowed examination of the chiroptical properties of the resulting enantiomers (λmax(abs)=593 nm, λmax(em)=622 nm, ϵ=30 000 m−1 cm−1, φF=0.49, |glum|=3.7×10−3 (hexane)). This is the first example of circularly polarised emission from a non-C2-symmetric helically chiral N,N,O,C-BODIPY and as such provides a valuable benchmark for future developments in this compound series
Determination of Metabolic Viability and Cell Mass Using a Tandem Resazurin/Sulforhodamine B Assay

The identification of rapid, reliable, and highly reproducible biological assays that can be standardized and routinely used in preclinical tests constitutes a promising approach to reducing drug discovery costs and time. This unit details a tandem, rapid, and reliable cell viability method for preliminary screening of chemical compounds. This assay measures metabolic activity and cell mass in the same cell sample using a dual resazurin/sulforhodamine B assay, eliminating the variation associated with cell seeding and excessive manipulations in assays that test different cell samples across plates. The procedure also reduces the amount of cells, test compound, and reagents required, as well as the time expended in conventional tests, thus resulting in a more confident prediction of toxic thresholds for the tested compounds. © 2016 by John Wiley & Sons, Inc