'I think it does just opens it up and you're not hiding it anymore': Trainee clinical psychologists' experiences of self-disclosing mental health difficulties.

Self-disclosure of experiences of mental health difficulties is a complex process, particularly within the workplace. Research shows that a significant number of trainee clinical psychologists have lived experience of mental health difficulties and thus face the dilemma of whether to disclose and how to manage self-disclosure during doctoral training. Grounded theory methodology was used to explore trainee experiences of self-disclosure of mental health difficulties during training. Twelve trainee clinical psychologists from accredited doctoral programmes in the United Kingdom participated in semi-structured interviews about their experiences of disclosure. Six core categories emerged relating to 'motivations', 'enablers', 'barriers', 'features of disclosure', 'responses' and 'impact', each of which were comprised of several further sub-categories. The model that emerged is largely consistent with research on disclosure in healthcare professions and has implications for training programmes, supervisors and trainees when engaging in conversations about lived experience.

Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing.

BACKGROUND: AABB standards state that cryoprecipitate should be transfused within 4 to 6 hours after thawing. We evaluated coagulation factor levels and sterility of thawed pooled cryoprecipitate to assess whether shelf life can be safely extended. STUDY DESIGN AND METHODS: Donor cryoprecipitate pools (n = 20, 10 group A, 10 group O) were held at ambient temperature and sampled at 0, 4, 8, 24, 48, 72, 96, and 120 hours post-thawing for fibrinogen, Factor (F)VIII, and von Willebrand factor (vWF) levels. Samples were tested at 0 and 120 hours for sterility (BacT/Alert system). Sixty additional cryoprecipitate pools were evaluated after 72 hours. Longitudinal differences in component levels were determined by linear fixed-effects regression. RESULTS: Group O cryoprecipitate had significantly lower FVIII (p = 0.002) and vWF activity (p = 0.006) compared to group A at 0 hours, but were not statistically different in fibrinogen levels (p = 0.33). Fibrinogen levels were stable over 5 days: 501 ± 81 mg/unit (mean ± standard deviation) at 0 hours to 506 ± 102 mg/unit at 120 hours (p = 0.73). Similarly, there was no decline in vWF activity: 200 ± 53 IU/unit at 0 hours to 209 ± 57 IU/unit at 120 hours (p = 0.084). The FVIII activity significantly declined on average by 9.6 IU (95% confidence interval, 5.5-13.8) between 0 hours (111 ± 33 IU/unit) and 120 hours post-thaw (101 ± 33) (p < 0.001). No organisms were detected when cryoprecipitate pools were cultured at 0 hours, but at 120 hours Staphylococcus epidermidis was identified from one pool, potentially a contaminant introduced during repeated sampling. No cultures were positive among the 60 additional cryoprecipitate pools assessed at 72 hours. CONCLUSION: Extended cryoprecipitate storage at ambient temperature did not affect fibrinogen levels over 120 hours. Sterility of products held at ambient temperature for an extended period of time could be assessed by secondary culture.

The experience of the long-term doctor-patient relationship in consultant nephrologists.

BACKGROUND: There is evidence to suggest that the long-term doctor-patient relationship is crucial in the management of chronic illness such as chronic kidney disease. While previous research has focused on patient views of the doctor-patient relationship, research exploring the doctor's experiences of this unique dynamic is lacking, leading to a gap in our understanding. Therefore, an enhanced appreciation of the experience of the doctor is important and could have potential implications for medical training and service organisation. OBJECTIVES: In this paper, we report the first known study exploring the experience of consultant nephrologists in the long-term doctor-patient relationship. PARTICIPANTS AND DESIGN: Seven male consultant nephrologists (mean age of 48 years) took part in semi-structured interviews, and data were analysed using interpretative phenomenological analysis (IPA). RESULTS: Three main themes were identified from the analysis: 'Defining my professional identity', 'Relating to the patient' and 'Coping with the job'. CONCLUSION: Participants had difficulty in defining their role as doctors, discussing themselves as being more than a doctor and comparing themselves with other medical specialties to help them define their identity. Although participants enjoyed forming long-term relationships with patients and the closeness this involved, they discussed the acute scenarios of saving lives as the most rewarding aspect of their job and used coping mechanisms that enabled them to remain detached in the relationship.

Click strategies for single-molecule protein fluorescence.

Single-molecule methods have matured into central tools for studies in biology. Foerster resonance energy transfer (FRET) techniques, in particular, have been widely applied to study biomolecular structure and dynamics. The major bottleneck for a facile and general application of these studies arises from the need to label biological samples site-specifically with suitable fluorescent dyes. In this work, we present an optimized strategy combining click chemistry and the genetic encoding of unnatural amino acids (UAAs) to overcome this limitation for proteins. We performed a systematic study with a variety of clickable UAAs and explored their potential for high-resolution single-molecule FRET (smFRET). We determined all parameters that are essential for successful single-molecule studies, such as accessibility of the probes, expression yield of proteins, and quantitative labeling. Our multiparameter fluorescence analysis allowed us to gain new insights into the effects and photophysical properties of fluorescent dyes linked to various UAAs for smFRET measurements. This led us to determine that, from the extended tool set that we now present, genetically encoding propargyllysine has major advantages for state-of-the-art measurements compared to other UAAs. Using this optimized system, we present a biocompatible one-step dual-labeling strategy of the regulatory protein RanBP3 with full labeling position freedom. Our technique allowed us then to determine that the region encompassing two FxFG repeat sequences adopts a disordered but collapsed state. RanBP3 serves here as a prototypical protein that, due to its multiple cysteines, size, and partially disordered structure, is not readily accessible to any of the typical structure determination techniques such as smFRET, NMR, and X-ray crystallography.

An investigation into the experience of self-conscious emotions in individuals with bipolar disorder, unipolar depression and non-psychiatric controls.

UNLABELLED: There has been little research into the association of shame and other self-conscious emotions in bipolar disorder, although there is evidence linking shame to various psychopathologies. OBJECTIVES: This research investigates the levels of shame in individuals with bipolar disorder. DESIGN AND METHODS: A cross-sectional design was used to compare 24 individuals with a diagnosis of bipolar disorder to a clinical control group of 18 individuals with unipolar depression, and 23 age-matched non-psychiatric controls on measures of mood (Beck Depression Inventory [BDI] and Self Report Manic Inventory [SRMI]) and of self-conscious emotions (Internalized Shame Scale and Test of Self-Conscious Affect). RESULTS: Higher levels of trait shame and lower guilt-proneness were found in the bipolar group. Higher levels of shame-proneness were found in the unipolar group in comparison to the bipolar and control groups. BDI scores positively correlated with trait shame and shame-proneness, and accounted for a large proportion of the variance in these scores. SRMI scores positively correlated with trait (internalized) shame and negatively correlated with guilt-proneness. CONCLUSIONS: There was evidence for the presence of shame within bipolar disorder, but this differed to the evidence for shame in individuals with unipolar depression. Clinical implications are discussed.

Mixed kappa/mu opioid receptor agonists: the 6 beta-naltrexamines.

Ligands from the naltrexamine series have consistently demonstrated agonist activity at kappa opioid receptors (KOR), with varying activity at the mu opioid receptor (MOR). Various 6 beta-cinnamoylamino derivatives were made with the aim of generating ligands with a KOR agonist/MOR partial agonist profile, as ligands with this activity may be of interest as treatment agents for cocaine abuse. The ligands all displayed the desired high affinity, nonselective binding in vitro and in the functional assays were high efficacy KOR agonists with some partial agonist activity at MOR. Two of the new ligands (12a, 12b) have been evaluated in vivo, with 12a acting as a KOR agonist and therefore somewhat similar to the previously evaluated analogues 3-6, while 12b displayed predominant MOR agonist activity.

Cinnamoyl derivatives of 7alpha-aminomethyl-6,14-endo-ethanotetrahydrothebaine and 7alpha-aminomethyl-6,14-endo-ethanotetrahydrooripavine and related opioid ligands.

A new series of ligands has been synthesized where the cinnamoyl group of the 14-cinnamoylamino morphinones has been introduced to the 7alpha-substituent of the 6,14-bridged oripavine series. In vitro the compounds were mostly low efficacy partial agonists or antagonists with some selectivity for the mu opioid receptor, with evidence of micro efficacy in vivo. The similarity in SAR between these 6,14-bridged oripavines and the 14-cinnamoylamino series suggests a similar mode of interaction with the micro opioid receptor.