Contribution of Reliable Chromatographic Data in QSAR for Modelling Bisphenol Transport across the Human Placenta Barrier.

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as BPAF, BPAP, BPB, BPF, BPP, BPS, and BPZ. However, these alternatives are under surveillance for potential endocrine disruption, particularly during the critical period of fetal development. Despite their structural analogies, these BPs differ greatly in their placental transport efficiency. For predicting the fetal exposure of this important class of emerging contaminants, quantitative structure-activity relationship (QSAR) studies were developed to model and predict the placental clearance indices (CI). The most usual input parameters were molecular descriptors obtained by modelling, but for bisphenols (BPs) with structural similarities or heteroatoms such as sulfur, these descriptors do not contrast greatly. This study evaluated and compared the capacity of QSAR models based either on molecular or chromatographic descriptors or a combination of both to predict the placental passage of BPs. These chromatographic descriptors include both the retention mechanism and the peak shape on columns that reflect specific molecular interactions between solute and stationary and mobile phases and are characteristic of the molecular structure of BPs. The chromatographic peak shape such as the asymmetry and tailing factors had more influence on predicting the placental passage than the usual retention parameters. Furthermore, the QSAR model, having the best prediction capacity, was obtained with the chromatographic descriptors alone and met the criteria of internal and cross validation. These QSAR models are crucial for predicting the fetal exposure of this important class of emerging contaminants.

Comparison of toxicokinetic properties of eleven analogues of Bisphenol A in pig after intravenous and oral administrations.

Due to the restrictions of its use, Bisphenol A (BPA) has been replaced by many structurally related bisphenols (BPs) in consumer products. The endocrine disrupting potential similar to that of BPA has been described for several bisphenols, there is therefore an urgent need of toxicokinetic (TK) data for these emerging BPs in order to evaluate if their internal exposure could increase the risk of endocrine disruption. We investigated TK behaviors of eleven BPA substitutes (BPS, BPAF, BPB, BPF, BPM, BPZ, 3-3BPA, BP4-4, BPAP, BPP, and BPFL) by intravenous and oral administrations of mixtures of them to piglets and serial collection of blood over 72 h and urine over 24 h, to evaluate their disposition. Data were analyzed using nonlinear mixed-effects modeling and a comparison was made with TK predicted by the generic model HTTK package. The low urinary excretion of some BPs, in particular BPM, BPP and BPFL, is an important aspect to consider in predicting human exposure based on urine biomonitoring. Despite their structural similarities, for the same oral dose, all BPA analogues investigated showed a higher systemic exposure (area under the plasma concentration-time curve (AUC) of the unconjugated Bisphenol) than BPA (2 to 4 fold for 3-3BPA, BPAF, BPB and BPZ, 7-20 fold for BP4-4, BPAP, BPP, BPFL, BPF and BPM and 150 fold for BPS) due mainly to a considerable variation of oral bioavailability (proportion of BP administered by oral route that attains the systemic circulation unchanged). Given similarities in the digestive tract between pigs and humans, our TK data suggest that replacing BPA with some of its alternatives, particularly BPS, will likely lead to higher internal exposure to potential endocrine disruptive compounds. These findings are crucial for evaluating the risk of human exposure to these emerging BPs.

Biomarkers of dietary patterns: a systematic review of randomized controlled trials.

CONTEXT: Most methods for assessing dietary intake have considerable measurement error. Dietary biomarkers are objective tools for dietary assessment. Dietary biomarkers of dietary patterns have not been well described, despite modern dietary guidelines endorsing dietary patterns. OBJECTIVE: This systematic review sought to describe the dietary biomarkers commonly used to assess dietary patterns, and the novel biomarkers of dietary patterns identified by exploratory studies. DATA SOURCES: MEDLINE, Embase, Cochrane Central, PreMEDLINE, and CINAHL databases were searched. DATA EXTRACTION: Data extraction and bias assessment were undertaken in duplicate. DATA ANALYSIS: A qualitative approach was applied, without statistical analysis. CONCLUSION: In controlled settings, dietary biomarkers of single nutrients or of individual foods or food groups are commonly used to assess compliance with dietary patterns. However, currently, there are no dietary biomarkers or biomarker profiles that are able to identify the specific dietary pattern that has been consumed by an individual. Future work should seek to validate novel dietary biomarkers and biomarker profiles that are indicative of specific dietary patterns and their characteristics. A dietary biomarker panel consisting of multiple biomarkers is almost certainly necessary to capture the complexity of dietary patterns. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019129839.

Comparison of the materno-fetal transfer of fifteen structurally related bisphenol analogues using an ex vivo human placental perfusion model.

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by a variety of alternatives in consumer products. Due to their structural similarity to BPA, these alternatives are under surveillance, however, for potential endocrine disruption. Understanding the materno-fetal transfer of these BPA-related alternatives across the placenta is therefore crucial to assess prenatal exposure risks. The objective of the study was to assess and compare the placental transfer of a set of 15 selected bisphenols (BPs) (BP 4-4, BPA, BPAF, BPAP, 3-3 BPA, BPB, BPBP, BPC, BPE, BPF, BPFL, BPM, BPP, BPS and BPZ) using the ex vivo human placental perfusion model. The UHPLC-MS/MS method for simultaneous quantification of these BPs in perfusion media, within a concentration range of 0.003-5 µM, was able to measure placenta transfer rates as low as 0.6%-4%. Despite their structural similarities, these BPs differed greatly in placental transport efficiency. The placental transfer rates of BP4-4, BPAP, BPE, BPF, 3-3BPA, BPB, BPA were similar to that of antipyrine, indicating that their main transport mechanism was passive diffusion. By contrast, the placental transfer rates of BPFL and BPS were very limited, and intermediate for BPBP, BPZ, BPC, BPM, BPP and BPAF, suggesting weak diffusional permeability and/or that their passage might involve efflux transport. These placental transfer data will be particularly useful for predicting the fetal exposure of this important class of emerging contaminants.

Assessing Self-Definition and Relatedness in Level of Personality Functioning.

The two polarities model (TPM) of personality organizes psychological assessment and psychotherapy and connects to personality disorder diagnosis using the DSM-5 Alternative Model for Personality Disorders (AMPD). The authors developed scales assessing the TPM from an existing self-report measure for level of personality functioning (LPF), a core component of the AMPD. Iterative content analyses of the LPF measure yielded scales for Autonomy and Communion corresponding to dimensions of the TPM. The scales were refined via internal consistency analyses using a measure of psychological attachment and studied in development and validation samples. Associations with relevant external criteria were explored in a series of multiple regressions. The new content-based LPF scales were illustrated with a case vignette. Although the new Autonomy/Communion scales await further validation prior to clinical use, initial evidence suggests that they may bridge the nomological nets of the TPM and AMPD and potentially offer clinical utility in assessment and treatment planning.

Quality of Internalized Object Representations and Suicidality in Individuals With Anaclitic and Introjective Personality Styles.

Research has shown differences in the characteristics of suicidal behavior in individuals with dependent (anaclitic) versus self-critical (introjective) personality styles. Questions remain, however, as to what factors distinguish suicidal from nonsuicidal individuals within each personality style. The current study examined clinical and interpersonal correlates of suicidality in 124 patients attending residential treatment for complex psychiatric disorders, with the aim of clarifying how social cognition and quality of internalized object representations relate to suicidality in individuals with anaclitic versus introjective personality organizations. Higher anaclitic and lower introjective traits each predicted higher frequency of prior attempts. Furthermore, higher anaclitic and lower introjective traits interacted with the affective-interpersonal quality of object representations to predict prior attempts, such that each trait was associated with more frequent past attempts in the context of poorer quality of object relations. The treatment implications of these findings are discussed, and areas for future research are considered.

Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success.

In the setting of myocardial infarction (MI), ischemia reperfusion injury (IRI) occurs due to occlusion (ischemia) and subsequent re-establishment of blood flow (reperfusion) of a coronary artery. A similar phenomenon is observed in heart transplantation (HTx) when, after cold storage, the donor heart is connected to the recipient's circulation. Although reperfusion is essential for the survival of cardiomyocytes, it paradoxically leads to additional myocardial damage in experimental MI and HTx models. Damage (or danger)-associated molecular patterns (DAMPs) are endogenous molecules released after cellular damage or stress such as myocardial IRI. DAMPs activate pattern recognition receptors (PRRs), and set in motion a complex signaling cascade resulting in the release of cytokines and a profound inflammatory reaction. This inflammatory response is thought to function as a double-edged sword. Although it enables removal of cell debris and promotes wound healing, DAMP mediated signalling can also exacerbate the inflammatory state in a disproportional matter, thereby leading to additional tissue damage. Upon MI, this leads to expansion of the infarcted area and deterioration of cardiac function in preclinical models. Eventually this culminates in adverse myocardial remodeling; a process that leads to increased myocardial fibrosis, gradual further loss of cardiomyocytes, left ventricular dilation and heart failure. Upon HTx, DAMPs aggravate ischemic damage, which results in more pronounced reperfusion injury that impacts cardiac function and increases the occurrence of primary graft dysfunction and graft rejection via cytokine release, cardiac edema, enhanced myocardial/endothelial damage and allograft fibrosis. Therapies targeting DAMPs or PRRs have predominantly been investigated in experimental models and are potentially cardioprotective. To date, however, none of these interventions have reached the clinical arena. In this review we summarize the current evidence of involvement of DAMPs and PRRs in the inflammatory response after MI and HTx. Furthermore, we will discuss various current therapeutic approaches targeting this complex interplay and provide possible reasons why clinical translation still fails.

Toxicokinetics of bisphenol S in rats for predicting human bisphenol S clearance from allometric scaling.

Previous data obtained in piglets suggested that despite structural analogy with Bisphenol A (BPA), Bisphenol S (BPS) elimination may proceed more slowly, resulting in a much higher systemic exposure to unconjugated BPS than to BPA. Interspecies allometric scaling was applied to predict the toxicokinetic (TK) parameters of BPS, namely plasma clearance in humans from values obtained in animals, and thus contribute to assessment of the human internal exposure to BPS. Allometric scaling was performed using mean BPS plasma clearance values measured in rats after intravenous administration of 5 mg BPS /kg body weight (BW) and those previously obtained in piglets and sheep using identical IV BPS dosing and analytical procedures. The BPS plasma clearance, evaluated at 0.92 L/kg.h in rats, was proportional to species body weight, enabling the prediction of human BPS plasma clearance by extrapolating to a BW of 70 kg. The estimated BPS plasma clearance in humans was thus 0.92 L/min (0.79 L/kg.h), i.e. about two times lower than the previously estimated BPA clearance (1.79 L/min). By increasing systemic exposure to the active moiety of an environmental estrogenic chemical, this less efficient clearance of BPS in humans, as compared with BPA, might worsen the harmful consequences of replacing BPA by BPS.

Oral Systemic Bioavailability of Bisphenol A and Bisphenol S in Pigs.

BACKGROUND: Given its hormonal activity, bisphenol S (BPS) as a substitute for bisphenol A (BPA) could actually increase the risk of endocrine disruption if its toxicokinetic (TK) properties, namely its oral availability and systemic persistency, were higher than those of BPA. OBJECTIVES: The TK behavior of BPA and BPS was investigated by administering the two compounds by intravenous and oral routes in piglet, a known valid model for investigating oral TK. METHODS: Experiments were conducted in piglets to evaluate the kinetics of BPA, BPS, and their glucuronoconjugated metabolites in plasma and urine after intravenous administration of BPA, BPS, and BPS glucuronide (BPSG) and gavage administration of BPA and BPS. A population semiphysiologically based TK model describing the disposition of BPA and BPS and their glucuronides was built from these data to estimate the key TK parameters that drive the internal exposure to active compounds. RESULTS: The data indicated that almost all the BPS oral dose was absorbed and transported into the liver where only 41% of BPS was glucuronidated, leading to a systemic bioavailability of 57.4%. In contrast, only 77% of the oral dose of BPA was absorbed and underwent an extensive first-pass glucuronidation either in the gut (44%) or in the liver (53%), thus accounting for the low systemic bioavailability of BPA (0.50%). Due to the higher systemic availability of BPS, in comparison with BPA, and its lower plasma clearance (3.5 times lower), the oral BPS systemic exposure was on average about 250 times higher than for BPA for an equal oral molar dose of the two compounds. CONCLUSION: Given the similar digestive tracts of pigs and humans, our results suggest that replacing BPA with BPS will likely lead to increased internal exposure to an endocrine-active compound that would be of concern for human health. https://doi.org/10.1289/EHP4599.

Is bisphenol S a safer alternative to bisphenol A in terms of potential fetal exposure ? Placental transfer across the perfused human placenta.

The aim of our study was to evaluate the bidirectional transfer of Bisphenol S (BPS) and its main metabolite, BPS Glucuronide (BPSG), using the model of perfused human placenta and to compare the obtained values with those of Bisphenol A (BPA) and BPA Glucuronide. Fourteen placentas at term were perfused in an open dual circuit with deuterated BPS (1 and 5 µM) and non-labelled BPSG (2.5 µM) and a freely diffusing marker antipyrine (800 ng/ml) in the presence of albumin (25 mg/ml). In a second experiment, the potential role of P-glycoprotein in the active efflux of BPS across the placental barrier was studied using the well-established P-glycoprotein inhibitor, PSC833 (2 and 4 µM). Placental transfer of BPS was much lower than that of BPA in both directions. The placental clearance index of BPS in the materno-fetal direction was three times lower than in the opposite direction, strongly suggesting some active efflux transport. However, our results show that P-glycoprotein is not involved in limiting the materno-fetal transfer of BPS. Placental transfer of BPSG in the fetal compartment was almost non-existent indicating that, in the fetal compartment, BPSG originates mainly from feto-placental metabolism. The feto-maternal clearance index for BPSG was 20-fold higher than the materno-fetal index. We conclude that the blood-placental barrier is much more efficient in limiting fetal exposure to BPS than to BPA, indicating that the placenta has a crucial role in protecting the human fetus from BPS exposure.

Flexibility and Rigidity in Object Relational Functioning: Assessing Change in Suicidal Ideation and Global Psychiatric Functioning Using the SCORS-G.

The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Westen, 1995 ) has been widely used as an assessment measure of object relational functioning across a number of stimuli. This study used the SCORS-G to investigate associations between global impairments and rigidity in quality of object relations with changes in suicidal ideation and psychiatric functioning over time. Participant narratives describing actual interpersonal experiences were collected using the Relationship Anecdote Paradigm (Luborsky, 1998 ) from a sample of individuals diagnosed with complex psychopathology completing residential psychiatric treatment. We found that a greater range in affective quality and emotional investment in relationship scores at admission into treatment were significantly related to a reduction in suicidal ideation as well as improvements in global psychiatric functioning at 5-year follow-up. Thus, participants who acknowledged having both healthy as well as troubled relationships in their daily lives were less suicidal and less likely to experience disruptive psychiatric symptoms over time than those who described more restricted or uniform relational experiences on entering treatment. Implications for calculating range scores and using various narrative techniques when applying the SCORS-G method are discussed.

The persistent shadow of suicide ideation and attempts in a high-risk group of psychiatric patients: A focus for intervention.

OBJECTIVE: Patients with a history of suicidal ideation or attempts, especially if they have serious psychopathology with repeated hospitalizations, are burdened by ongoing risk for suicide. We studied this high-risk group to assess their psychological status following their most recent suicide attempt, in contrast to equally ill patients without a suicide history. Further, among suicidal patients, we compared those with only ideation, with a non-medically serious suicide attempt and with medically serious suicide attempts. We also report on the development of a new measure of psychic pain. METHODS: Patients in residential treatment (n=131) completed self-report questionnaires about suicide history, impulsiveness, psychic pain, resilience, and reasons for living. A series of univariate ordinal logistic regressions identified variables to include in a multivariable logistic regression to examine the odds associated with increasing levels of suicidality. RESULTS: A history of suicidal ideation or suicide attempts is associated with proportionally more psychic pain and fewer current reasons for living. Prior history of abuse, impulsiveness, and general resilience were not significantly associated with suicidal severity. CONCLUSIONS: For patients who have suicidal ideation, or have attempted suicide, and also have additional risk factors including past hospitalization, treatments should include both understanding the sources of psychic pain and promoting individual discovery of reasons for living.

Suicidality in High-Risk Psychiatric Patients: The Contribution of Protective Factors.

OBJECTIVE: This study's objective was determine the incremental association of reasons for living to the lifetime number of suicide attempts in relation to other known risk and protective factors in a sample of psychiatric patients with extensive psychopathology in residential treatment. METHODS: Participants (n = 131) completed a demographic questionnaire that also asked for information about lifetime suicide history, psychiatric history, trauma, and abuse history. Additional measures of resilience, reasons for living (RFL), and impulsiveness were completed. RESULTS: A history of sexual abuse was associated with an increasing lifetime number of suicide attempts, while a history of physical abuse and trait impulsiveness were not associated with the lifetime number of suicide attempts. Survival and coping beliefs, a subscale of the Reasons for Living Inventory (RFLI), was found to add incremental predictive validity to the number of lifetime suicide attempts. A composite fear variable, combining fear of suicide and fear of social consequences of suicide, was negatively correlated with lifetime number of attempts but did not add incremental validity to the prediction of lifetime number of suicide attempts. CONCLUSION: In a sample of participants with significant psychiatric impairment, the protective factor of survival and coping beliefs may be an important barrier to repeated suicide attempts and may be considered a suicide-specific resilience measure. Understanding the psychological processes contributing to the development of such protective factors as resilience, meaning in life, and coping resources is an important area of study and a potential avenue for targeted therapeutic intervention in high-risk populations.

Insight as a social identity process in the evolution of psychosocial functioning in the early phase of psychosis.

BACKGROUND: Awareness of illness (insight) has been found to have contradictory effects for different functional outcomes after the early course of psychosis. Whereas it is related to psychotic symptom reduction and medication adherence, it is also associated with increased depressive symptoms. In this line, the specific effects of insight on the evolution of functioning over time have not been identified, and social indicators, such as socio-occupational functioning have barely been considered. Drawing from social identity theory we investigated the impact of insight on the development of psychosocial outcomes and the interactions of these variables over time. METHOD: The participants, 240 patients in early phase of psychosis from the Treatment and Early Intervention in Psychosis Program (TIPP) of the University Hospital of Lausanne, Switzerland, were assessed at eight time points over 3 years. Cross-lagged panel analyses and multilevel analyses were conducted on socio-occupational and general functioning [Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF)] with insight, time and depressive symptoms as independent variables. RESULTS: Results from multilevel analyses point to an overall positive impact of insight on psychosocial functioning, which increases over time. Yet the cross-lagged panel analysis did not reveal a systematic positive and causal effect of insight on SOFAS and GAF scores. Depressive symptoms seem only to be relevant in the beginning of the treatment process. CONCLUSIONS: Our results point to a complex process in which the positive impact of insight on psychosocial functioning increases over time, even when considering depressive symptoms. Future studies and treatment approaches should consider the procedural aspect of insight.

Multispecialty screening, brief intervention, and referral to treatment (SBIRT) training in an academic medical center: Resident training experience across specialties.

BACKGROUND: The Substance Abuse and Mental Health Services Administration (SAMHSA) has recently begun to fund programs that train medical residents on how to utilize an evidence-based validated system known as screening, brief intervention, and referral to treatment (SBIRT) for providing early detection and brief treatment of unhealthy substance use. This paper investigates training outcomes of multispecialty SBIRT training at one such program at Albany Medical Center (AMC), one of the initial SAMHSA grantees. METHODS: Training outcomes were measured across 3 domains of learning: trainee satisfaction, acquired knowledge, and perceived usefulness. The authors explored differences in learning experience by postgraduate year and by specialty. RESULTS: Overall, residents were highly satisfied with the training, and learning outcomes met objectives. Residents' ratings of usefulness did not vary by program year. However, the results indicate that relative to residents in other programs, residents in psychiatry and pediatrics found the training components significantly more useful, whereas emergency medicine residents found training components to have less utility. Residents who found the training relevant to their daily work were more satisfied and more receptive to SBIRT training overall, which may help explain difference scores by program. CONCLUSIONS: Residents were highly satisfied with SBIRT skills training, although ratings of usefulness varied by residency program. Specialization by program and on-site modeling by senior faculty may enhance trainee satisfaction and perceived usefulness.

Impairments in Object Relations and Chronicity of Suicidal Behavior in Individuals With Borderline Personality Disorder.

While studies have demonstrated connections between impairments in object relations and self-destructive behaviors in individuals with borderline personality disorder (BPD), few have investigated whether these impairments relate to actual suicidal behaviors. The current study utilized the Social Cognition and Object Relations Scale-Global Method to investigate object relational functioning and suicidal behaviors in 131 residential treatment patients. Cognitive but not affective aspects of internalized representations predicted past suicidal behavior in BPD subjects; no relationships were found between quality of object representations and suicide in other-PD subjects. Implications of these findings for research, theory, and treatment of suicidal individuals are discussed.

Residents' experience of screening, brief intervention, and referral to treatment (SBIRT) as a clinical tool following practical application: A mixed-methods study.

BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT), an evidence-based validated system for providing early detection and brief treatment of substance use disorders, has been widely used in the training of medical residents across specialties at a number of sites. This article investigates the effectiveness of SBIRT training during short-term follow-up at Albany Medical Center, one of the initial Substance Abuse and Mental Health Services Administration (SAMHSA) grantees. METHODS: Training outcomes were measured by training satisfaction following opportunities to apply SBIRT skills in clinical work, the rate at which these techniques were applied in clinical work, and the degree to which residents felt that the SBIRT training provided skills that were applicable to their practice. We examined differences in learning experience by postgraduate year and by program, and conducted a qualitative analysis in a convergent parallel mixed-methods design to elucidate barriers encountered by residents upon using SBIRT techniques in clinical practice. RESULTS: Residents remained highly satisfied with the training at 4-month follow-up, with 80.1% reporting that they had used SBIRT skills in their clinical work. Use of SBIRT techniques was high at 6-month follow-up as well, with 85.9% of residents reporting that they regularly screened their patients for substance use, 74.4% reporting that they had applied brief intervention techniques, and 78.2% indicating that SBIRT training had made them overall more effective in helping patients with substance use issues. Differences in application rates and satisfaction were found by specialty. Qualitative analyses indicated that residents encountered patient readiness and specific contextual factors, such as time constraints, externally imposed values, and clinical norms, as barriers to implementation. CONCLUSIONS: Despite encountering obstacles such as time constraints and patient readiness, residents utilized many of the skills they had learned during SBIRT training in clinical practice and reported finding these skills useful in their management of patients with substance use issues.

Inhabitants' and professionals' social representations of health determinants in a disadvantaged urban area in France: a qualitative analysis.

BACKGROUND AND OBJECTIVE: Access to care in French disadvantaged urban areas remains an issue despite the implementation of local healthcare structures. To understand this contradiction, we investigated social representations held by inhabitants of such areas, as well as those of social and healthcare professionals, regarding events or behaviours that can impact low-income individuals' health. METHOD: In the context of a health diagnosis, 288 inhabitants living in five disadvantaged districts of Aix-les-Bains, as well as 28 professionals working in these districts, completed an open-ended questionnaire. The two groups of respondents were asked to describe what could have an impact on health status from the inhabitants' point of view. The textual responses were analyzed using the Alceste method. RESULTS: We observed a number of differences in the way the inhabitants and professionals represented determinants of health in disadvantaged urban areas: the former proposed a representation mixing personal responsibility with physiological, social, familial, and professional aspects, whereas the latter associated health issues with marginalization (financial, drug, or alcohol problems) and personal responsibility. Both inhabitants and professionals mentioned control over events and lifestyle as determinants of health. DISCUSSION: The results are discussed regarding the consequences of these different representations on the beneficiary - healthcare-provider relationship in terms of communication and trust.

Microprocess examination of therapeutic immediacy during a dynamic research interview.

This study examines the interviewer's use of immediacy during a dynamic interview to enhance the patient's ability to process affective material and deepen personal exploration. Using a microprocess design, immediacy events were identified and rated using the Consensual Qualitative Rating method. Moment-to-moment in-session activity was rated by trained observers with a focus on measuring patient process using the Therapist-Patient Interaction Rating Scale and interviewer process using the Therapeutic Environment Scale. Five immediacy events were identified and were found to range in depth from mundane exchanges to more active exchanges with affective depth. Mundane events were characterized by little attention to the affective component of the here-and-now relationship, dismissive and unsupportive comments, and had either no effect, or a negative effect on patient process. In contrast, immediacy events characterized by even limited affect and acknowledging engagement between patient and interviewer were followed by greater patient disclosure and increased capacity to process emotional information. Thus, attention to the quality of the immediacy intervention in future research appears warranted.