Patient’s and the Therapist’s Attachment Representations, Attachment to Therapists, and Self-Esteem-Change Through Psychotherapy

Objectives: The present naturalistic study aims to investigate the differential effects of the patient’s and the therapist’s attachment representations on the attachment to the therapist as perceived by the patient, and their impact on self-esteem-change through psychotherapy.Methods: Attachment variables of N = 573 patients as well as N = 16 therapists were assessed. Attachment representations were measured for therapists and patients via the Bielefelder Questionnaire for Client Attachment Exploration, the Relationship Specific Attachment to Therapist Scales and the Adult Attachment Interview. The patient’s attachment to therapists was evaluated and patients’ self-esteem was measured via the Frankfurter Selbstkonzeptskalen at the beginning and end of psychotherapy.Results: Although there were significant effects of the patient’s attachment representations on the perceived attachment to the therapist as well as between the perceived attachment to the therapist and the amount of self-esteem-change, the therapist’s attachment style had no significant influence on the perceived attachment to the therapist.Conclusion: Self-esteem-change through psychotherapy is influenced by the actually formed attachment relationship as perceived by the patient. The patient’s attachment representations but not the therapist’s attachment style contributes to the actual patient’s attachment to the therapist.

Modular self-assembly system for development of oligomeric, highly internalizing and potent cytotoxic conjugates targeting fibroblast growth factor receptors

Background Overexpression of FGFR1 is observed in numerous tumors and therefore this receptor constitutes an attractive molecular target for selective cancer treatment with cytotoxic conjugates. The success of cancer therapy with cytotoxic conjugates largely relies on the precise recognition of a cancer-specific marker by a targeting molecule within the conjugate and its subsequent cellular internalization by receptor mediated endocytosis. We have recently demonstrated that efficiency and mechanism of FGFR1 internalization are governed by spatial distribution of the receptor in the plasma membrane, where clustering of FGFR1 into larger oligomers stimulated fast and highly efficient uptake of the receptor by simultaneous engagement of multiple endocytic routes. Based on these findings we aimed to develop a modular, self-assembly system for generation of oligomeric cytotoxic conjugates, capable of FGFR1 clustering, for targeting FGFR1-overproducing cancer cells. Methods Engineered FGF1 was used as FGFR1-recognition molecule and tailored for enhanced stability and site-specific attachment of the cytotoxic drug. Modified streptavidin, allowing for controlled oligomerization of FGF1 variant was used for self-assembly of well-defined FGF1 oligomers of different valency and oligomeric cytotoxic conjugate. Protein biochemistry methods were applied to obtain highly pure FGF1 oligomers and the oligomeric cytotoxic conjugate. Diverse biophysical, biochemical and cell biology tests were used to evaluate FGFR1 binding, internalization and the cytotoxicity of obtained oligomers. Results Developed multivalent FGF1 complexes are characterized by well-defined architecture, enhanced FGFR1 binding and improved cellular uptake. This successful strategy was applied to construct tetrameric cytotoxic conjugate targeting FGFR1-producing cancer cells. We have shown that enhanced affinity for the receptor and improved internalization result in a superior cytotoxicity of the tetrameric conjugate compared to the monomeric one. Conclusions Our data implicate that oligomerization of the targeting molecules constitutes an attractive strategy for improvement of the cytotoxicity of conjugates recognizing cancer-specific biomarkers. Importantly, the presented approach can be easily adapted for other tumor markers.

Intersection of Redox Chemistry and Ubiquitylation: Post-Translational Modifications Required for Maintaining Cellular Homeostasis and Neuroprotection

Neurodegeneration has been predominantly recognized as neuronal breakdown induced by the accumulation of aggregated and/or misfolded proteins and remains a preliminary factor in age-dependent disease. Recently, critical regulating molecular mechanisms and cellular pathways have been shown to induce neurodegeneration long before aggregate accumulation could occur. Although this opens the possibility of identifying biomarkers for early onset diagnosis, many of these pathways vary in their modes of dysfunction while presenting similar clinical phenotypes. With selectivity remaining difficult, it is promising that these neuroprotective pathways are regulated through the ubiquitin-proteasome system (UPS). This essential post-translational modification (PTM) involves the specific attachment of ubiquitin onto a substrate, specifically marking the ubiquitin-tagged protein for its intracellular fate based upon the site of attachment, the ubiquitin chain type built, and isopeptide linkages between different ubiquitin moieties. This review highlights both the direct and indirect impact ubiquitylation has in oxidative stress response and neuroprotection, and how irregularities in these intricate processes lead towards the onset of neurodegenerative disease (NDD).

Diagnostic Value of the Fimbriae Distribution Pattern in Localization of Urinary Tract Infection

Urinary tract infections (UTIs) are one of the most common infectious diseases. UTIs are mainly caused by uropathogenic Escherichia coli (UPEC), and are either upper or lower according to the infection site. Fimbriae are necessary for UPEC to adhere to the host uroepithelium, and are abundant and diverse in UPEC strains. Although great progress has been made in determining the roles of different types of fimbriae in UPEC colonization, the contributions of multiple fimbriae to site-specific attachment also need to be considered. Therefore, the distribution patterns of 22 fimbrial genes in 90 UPEC strains from patients diagnosed with upper or lower UTIs were analyzed using PCR. The distribution patterns correlated with the infection sites, an XGBoost model with a mean accuracy of 83.33% and a mean area under the curve (AUC) of the receiver operating characteristic (ROC) of 0.92 demonstrated that fimbrial gene distribution patterns could predict the localization of upper and lower UTIs.

Social dialogue triggers biobehavioral synchrony of partners' endocrine response via sex-specific, hormone-specific, attachment-specific mechanisms

Social contact is known to impact the partners' physiology and behavior but the mechanisms underpinning such inter-partner influences are far from clear. Guided by the biobehavioral synchrony conceptual frame, we examined how social dialogue shapes the partners' multi-system endocrine response as mediated by behavioral synchrony. To address sex-specific, hormone-specific, attachment-specific mechanisms, we recruited 82 man–woman pairs (N = 164 participants) in three attachment groups; long-term couples (n = 29), best friends (n = 26), and ingroup strangers (n = 27). We used salivary measures of oxytocin (OT), cortisol (CT), testosterone (T), and secretory immuglobolinA (s-IgA), biomarker of the immune system, before and after a 30-min social dialogue. Dialogue increased oxytocin and reduced cortisol and testosterone. Cross-person cross-hormone influences indicated that dialogue carries distinct effects on women and men as mediated by social behavior and attachment status. Men's baseline stress-related biomarkers showed both direct hormone-to-hormone associations and, via attachment status and behavioral synchrony, impacted women's post-dialogue biomarkers of stress, affiliation, and immunity. In contrast, women's baseline stress biomarkers linked with men's stress response only through the mediating role of behavioral synchrony. As to affiliation biomarkers, men's initial OT impacted women's OT response only through behavioral synchrony, whereas women's baseline OT was directly related to men's post-dialogue OT levels. Findings pinpoint the neuroendocrine advantage of social dialogue, suggest that women are more sensitive to signs of men's initial stress and social status, and describe behavior-based mechanisms by which human attachments create a coupled biology toward greater well-being and resilience.

Attachment characteristics and emotion regulation difficulties among maladaptive and normal daydreamers

Maladaptive daydreaming is an excessive form of daydreaming which causes significant distress and functional impairment to the affected individuals. Research on maladaptive daydreaming has intensified in recent years, but its pathogenesis has not yet been clearly elucidated. The aim of the study was to examine the attachment characteristics and the difficulties in emotion regulation among maladaptive and normal daydreamers. 717 individuals were recruited online, 106 of whom were screened as maladaptive daydreamers. The results of the Attachment Style Questionnaire revealed a specific attachment style among maladaptive daydreamers, who were characterized by ‘Ambivalent-fearful’ attachment characteristics, while normal daydreamers showed ‘Secure-independent’ attachment style. Regarding emotion regulation difficulties, maladaptive daydreamers showed a significantly higher level of deficit on each subscale of the Difficulties in Emotion Regulation Scale compared to normal daydreamers. The findings highlighted the potential role of early attachment experiences in the etiology and pathogenesis of maladaptive daydreaming, as well as the presence of severe emotion regulation deficits among problematic daydreamers. The results revealed by the present study might give contributions to the development of psychotherapeutical treatment of maladaptive daydreaming.

Mind the Gap: Perceived Partner Responsiveness as a Bridge between General and Partner-Specific Attachment Security

A core idea of attachment theory is that security develops when attachment figures are responsive to a person’s connection needs. Individuals may be more or less secure in different relationships. We hypothesized that individuals who perceive a current relationship partner as being responsive to their needs will feel more secure in that specific relationship, and that the benefits of perceived partner responsiveness would be more pronounced for individuals who generally feel insecure. The current study included 472 individuals (236 couples) in romantic relationships. Consistent with our predictions, individuals who perceived more responsiveness from their partner displayed lower partner-specific attachment anxiety and partner-specific avoidance, especially when they were generally insecure. These findings are discussed in terms of the conditions that promote secure attachment bonds.

Relationship Between the Family Roles and Attachment Styles Among Adult Children of Alcoholic Fathers in Pakistan

Studies suggest that alcoholism is on the rise around the world, with many individuals facing the damaging consequences of this affliction. Children of Alcoholics (COAs) deal with several psychosocial issues that manifest themselves in the forms of defense mechanisms, or roles which affect their attachment styles and personal relationships. Purposive sampling was used on 398 participants (201 males, 197 females). The first one was for the participants (18 to 25 age range, the minimum level of education: tenth grade). The second was the fathers of the adult children, admitted in rehabilitation for alcoholism. The third foundation for setting the criteria was the family (a nuclear family system and has at least three siblings). A chisquare test for independence was significant [x2 (8, N = 398) = 433.551, p < .001], indicating that adult COAs with specific attachment styles are prone to take on certain roles within the family.

Today You Care, Tomorrow You Don’t: Differential Roles of Responsiveness Variability and Average Responsiveness in Romantic Attachment

Past work has shown that perceived responsiveness is a key predictor of relational outcomes. However, this work has focused solely on average levels of responsiveness and never studied the role of responsiveness variability (consistency of responsiveness) in intimate relationships. The present study addressed this gap by investigating the long-held but scarcely tested tenet that responsiveness variability and average responsiveness play differential roles in romantic attachment. New romantic couples ( N = 151) reported partner-specific attachment anxiety and avoidance in six sessions. Every evening during the 3-week period in between the first two sessions, participants reported perceived partner responsiveness, allowing us to assess both average responsiveness and responsiveness variability. Our findings provided the first empirical evidence that responsiveness variability uniquely predicted increases in partner-specific attachment anxiety, whereas average responsiveness uniquely predicted decreases in partner-specific attachment avoidance. Average responsiveness and responsiveness variability continued to predict attachment orientations assessed about half a year later.