Teaching problem-oriented therapy

The therapeutic concept is problem- and patient-oriented. In analogy to it the didactic concept is problem- and therapist-oriented. The essential point is learning in groups from practical cases. Problem-oriented in this context means that the problems-solving process in which the patient and the therapist are engaged is supported by the observer group. Therapist-oriented means that the learning process should take account of the different preferences and experiences of the therapists. That can only be accomplished by problem-oriented learning. Each psychotherapy training group consists of 4 assistant doctors and a supervisor and stays together about 1 year. The strongly structured concept of problem-oriented therapy (POT) [Blaser et al., 1988] offers the beginner a framework by which he can guide the dialogue with the patient. The eclecticism of POT allows the more experienced therapist to try out new methods without losing track of the problem. The constantly changing role of being observer or therapist supports the group coherence, and furthermore it promotes an important element of therapeutic competence, the ability to get into a close relation with the patient and at the same time being able to observe oneself, the patient and the therapeutic process from a more distant view. In addition to the POT training group tutorials in special psychotherapy methods and single supervision sessions are offered.     

What's an integrationist? A study of self‐identified integrative and (occasionally) eclectic psychologists

We examined the views and practices of self-identified eclectic and integrative psychologists, particularly in the context of historical changes since 1977 and 1988. Results from 187 eclectic clinical psychologists indicated that 50% previously adhered to another theoretical orientation, the majority preferred the term integrative to eclectic, and 85% conceptualized eclecticism/integration as the endorsement of a broader orientation. The most common paths toward integration were theoretical integration, common factors, and assimilative integration, as opposed to technical eclecticism. The most frequent theoretical contributor to integrative practice was cognitive therapy.     

Common Factors Aren't So Common: The Common Factors Dilemma

There is apparently little difference in the effectiveness of different kinds of psychotherapy. One explanation is that common factors cut across them. The major schools do not much attend to common factors, however, and it may be that outcome equivalence is due as much to common neglect of common factors as to their use. Five common factors are discussed: the therapeutic relationship, expectations, confronting problems, mastery, and attribution of outcome. Linear conceptions of causality seem to contribute to the problem of selective neglect of common factors, and it is suggested that reciprocal interaction may constitute a more viable way of understanding therapeutic processes. Although technical eclecticism and therapy integration have been proposed as potentially integrating the common factors, eclecticism lacks theoretical coherence, and viable integrations have yet to be offered, although statistical methods for testing them (causal modeling) may exist. To suggest what a productive integration could look like, a clinical example is connected metaphorically to a developmental model of attachment. Strategies for further research are also suggested.     

What Do We Mean by ‘Psychodynamic’? A Contribution to the Development of a Model

I hope to make a preliminary contribution to the development of a model that more clearly reformulates the practices of psychoanalytic psychotherapy in a way that recognizes a diversity of analytic practice that I think has been misdescribed - technically and politically - as 'psychodynamic'. The paper firstly considers the question of definition and suggests four identifiable meanings of the term' psychodynamic'. The discussion then reviews a number of core and inextricably connected questions of theory and practice under the following headings: setting and regression, time and frequency, countertransference, creativity and the real relationship, interpretation and pure technique, and the problem of eclecticism. The paper concludes by briefly exploring the parameters of psychodynamic practice in relation to eclecticism in psychotherapy, and makes a plea for a model that is consistent, authentic and ecumenical.     

Eclecticism and Integration in Psychotherapy: Developments and Issues

This article describes the popularity of eclecticism among clinical psychologists and related professional groups over the past 35 years and the more recent growth and development of the Integration movement in psychotherapy. Although these two emphases share a common view or value system of not restricting one's psychotherapy to only one theoretical orientation, they also appear to differ in important ways. Some of these differences are discussed as well as problems in research and training.     

POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex

Human telomere length is controlled by a negative feedback loop based on the binding of TRF1 to double-stranded telomeric DNA. The TRF1 complex recruits POT1, a single-stranded telomeric DNA-binding protein necessary for cis-inhibition of telomerase. By mass spectrometry, we have identified a new telomeric protein, which we have named POT1-interacting protein 1 (PIP1). PIP1 bound both POT1 and the TRF1-interacting factor TIN2 and could tether POT1 to the TRF1 complex. Reduction of PIP1 or POT1 levels with shRNAs led to telomere elongation, indicating that PIP1 contributes to telomere length control through recruitment of POT1.     

The intrinsically disordered N-terminal region of mouse DNA polymerase alpha mediates its interaction with POT1a/b at telomeres

Mouse telomerase and the DNA polymerase alpha-primase complex elongate the leading and lagging strands of telomeres, respectively. To elucidate the molecular mechanism of lagging strand synthesis, we investigated the interaction between DNA polymerase alpha and two paralogs of the mouse POT1 telomere-binding protein (POT1a and POT1b). Yeast two-hybrid analysis and a glutathione S-transferase pull-down assay indicated that the C-terminal region of POT1a/b binds to the intrinsically disordered N-terminal region of p180, the catalytic subunit of mouse DNA polymerase alpha. Subcellular distribution analyses showed that although POT1a, POT1b, and TPP1 were localized to the cytoplasm, POT1a-TPP1 and POT1b-TPP1 coexpressed with TIN2 localized to the nucleus in a TIN2 dose-dependent manner. Coimmunoprecipitation and cell cycle synchronization experiments indicated that POT1b-TPP1-TIN2 was more strongly associated with p180 than POT1a-TPP1-TIN2, and this complex accumulated during the S phase. Fluorescence in situ hybridization and proximity ligation assays showed that POT1a and POT1b interacted with p180 and TIN2 on telomeric chromatin. Based on the present study and a previous study, we propose a model in which POT1a/b-TPP1-TIN2 translocates into the nucleus in a TIN2 dose-dependent manner to target the telomere, where POT1a/b interacts with DNA polymerase alpha for recruitment at the telomere for lagging strand synthesis.     

Human POT1 is required for efficient telomere C-rich strand replication in the absence of WRN

Mechanisms of telomere replication remain poorly defined. It has been suggested that G-rich telomeric strand replication by lagging mechanisms requires, in a stochastic way, the WRN protein. Here we show that this requirement is more systematic than previously thought. Our data are compatible with a situation in which, in the absence of WRN, DNA synthesis at replication forks is uncoupled, thus allowing replication to continue on the C strand, while single G strands accumulate. We also show that in cells in which both WRN and POT1 are limiting, both G- and C-rich telomeric strands shorten, suggesting a complete replication block. Under this particular condition, expression of a fragment spanning the two POT1-OB (oligonucleotide-binding) fold domains is able to restore C (but not G) strand replication, suggesting that binding of POT1 to the lagging strand allows DNA synthesis uncoupling in the absence of WRN. Furthermore, in vitro experiments indicate that purified POT1 has a higher affinity for the telomeric G-rich strand than purified RPA. We propose a model in which the relative enrichments of POT1 versus RPA on the telomeric lagging strand allows or does not allow uncoupling of DNA synthesis at the replication fork. Our study reveals an unanticipated role for hPOT1 during telomere replication.     

A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus

Coats plus (CP) can be caused by mutations in the CTC1 component of CST, which promotes polymerase α (polα)/primase-dependent fill-in throughout the genome and at telomeres. The cellular pathology relating to CP has not been established. We identified a homozygous POT1 S322L substitution (POT1^CP) in two siblings with CP. POT1^CP induced a proliferative arrest that could be bypassed by telomerase. POT1^CP was expressed at normal levels, bound TPP1 and telomeres, and blocked ATR signaling. POT1^CP was defective in regulating telomerase, leading to telomere elongation rather than the telomere shortening observed in other telomeropathies. POT1^CP was also defective in the maintenance of the telomeric C strand, causing extended 3′ overhangs and stochastic telomere truncations that could be healed by telomerase. Consistent with shortening of the telomeric C strand, metaphase chromosomes showed loss of telomeres synthesized by leading strand DNA synthesis. We propose that CP is caused by a defect in POT1/CST-dependent telomere fill-in. We further propose that deficiency in the fill-in step generates truncated telomeres that halt proliferation in cells lacking telomerase, whereas, in tissues expressing telomerase (e.g., bone marrow), the truncations are healed. The proposed etiology can explain why CP presents with features distinct from those associated with telomerase defects (e.g., dyskeratosis congenita).     

Mutations in POT1 predispose to familial cutaneous malignant melanoma

POT1 loss‐of‐function variants predispose to familial melanoma Robles‐Espinoza et al. (2014) Nat Genet 46(5):478–481 Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma Shi et al. (2014) Nat Genet 46(5):482–486     

Functional interaction between telomere protein TPP1 and telomerase

Human chromosome end-capping and telomerase regulation require POT1 (Protection of Telomeres 1) and TPP1 proteins, which bind to the 3′ ssDNA extension of human telomeres. POT1–TPP1 binding to telomeric DNA activates telomerase repeat addition processivity. We now provide evidence that this POT1–TPP1 activation requires specific interactions with telomerase, rather than it being a DNA substrate-specific effect. First, telomerase from the fish medaka, which extends the same telomeric DNA primer as human telomerase, was not activated by human POT1–TPP1. Second, mutation of a conserved glycine, Gly100 in the TEN (telomerase essential N-terminal) domain of TERT, abolished the enhancement of telomerase processivity by POT1–TPP1, in contrast to other single amino acid mutations. Chimeric human–fish telomerases that contained the human TEN domain were active but not stimulated by POT1–TPP1, showing that additional determinants of processivity lie outside the TEN domain. Finally, primers bound to mouse POT1A and human TPP1 were activated for extension by human telomerase, whereas mPOT1A–mTPP1 was most active with mouse telomerase, indicating that these mammalian telomerases have specificity for their respective TPP1 proteins. We suggest that a sequence-specific interaction between TPP1 in the TPP1–POT1–telomeric DNA complex and the G100 region of the TEN domain of TERT is necessary for high-processivity telomerase action.     

介绍一种改进的、简便的凝胶迁移滞留试验法

目的 :改进凝胶迁移滞留试验 (EMSA)方法 ,运用该法检测新蛋白。方法 :抽提与定量核蛋白、DNA探针标记与纯化 ,探针与蛋白质的结合、电泳及放射自显影。结果 :采用本法简便、节约、灵敏度高、图像清晰、有可比性及重复性 ,成功运用于NF-κB及POT蛋白的检测。结论 :此法在本实验组运用过 ,可靠 ,值得应用与推广。     

The workload of general practitioners does not affect their awareness of patients' psychological problems

OBJECTIVE: To investigate if general practitioners (GPs) with a higher workload are less inclined to encourage their patients to disclose psychological problems, and are less aware of their patients' psychological problems. METHODS: Data from 2095 videotaped consultations from a representative selection of 142 Dutch GPs were used. Multilevel regression analyses were performed with the GPs' awareness of the patient's psychological problems and their communication as outcome measures, the GPs' workload as a predictor, and GP and patient characteristics as confounders. RESULTS: GPs' workload is not related to their awareness of psychological problems and hardly related to their communication, except for the finding that a GP with a subjective experience of a lack of time is less patient-centred. Showing eye contact or empathy and asking questions about psychological or social topics are associated with more awareness of patients' psychological problems. CONCLUSION: Patients' feelings of distress are more important for GPs' communication and their awareness of patients' psychological problems than a long patient list or busy moment of the day. GPs who encourage the patient to disclose their psychological problems are more aware of psychological problems. PRACTICE IMPLICATIONS: We recommend that attention is given to all the communication skills required to discuss psychological problems, both in the consulting room and in GPs' training. Additionally, attention for gender differences and stress management is recommended in GPs' training.     

Patient and public education for cholesterol reduction: a review of strategies and issues.

Elevated blood cholesterol is a major risk factor for coronary heart disease and a significant public health problem, affecting as many as 50% of all adults in the U.S. Public, professional and patient education are central to current widespread efforts to increase awareness and effective management of high cholesterol. Screening/case-finding, follow-up and nutrition education are the most widely applicable strategies for cholesterol reduction. The following topics are reviewed: current guidelines for treatment of elevated cholesterol levels; trends in awareness, attitudes and practices of the public and health professionals; reports of interventions for cholesterol reduction; and health policy issues and research needs related to cholesterol education. This review suggests that several major challenges lie ahead for widespread and effective educational management of high cholesterol levels. These include development of practical screening and education systems, establishment of feasible financing arrangements, effective communication of complex information to patients, and techniques for long-term maintenance of reductions in cholesterol levels.     

"Advising Oliver Mann"--a case-based, small-group orientation to medical school.

In 1998, the authors implemented a new academic orientation built around a problem-based clinical exercise for entering medical students, to prepare them for a curriculum emphasizing active learning in small groups. The exercise enables students to begin their professional studies with a "hands on" understanding of two major emphases of the curriculum: (1) the process of small-group learning that will guide their medical education and (2) the principles of patient care that will guide their future practice of medicine. Called "Advising Oliver Mann," this orientation presents students with a clinical problem that they must work in small groups to solve. By collaborating in teams of ten, they become acquainted with the small-group learning methods at the heart of the school's curriculum. Through solving a clinical problem, they discover vital principles of patient care, such as the need in clinical decision making to integrate the scientific perspective with the perspective of patient and family. In developing "Oliver Mann," the authors came to realize that orientations can be much more than introductions. They can be reflective moments in a busy curriculum, a time for students and faculty to step back and take stock of important issues in education and doctoring. The authors are currently experimenting with exercises linking their freshman orientation with orientations in the second and third years so participants can reflect on the challenges of each new year and carry forward the small-group methods and practice of medicine themes of the new curriculum.     

Characterization of POT1 tumor predisposition syndrome: Tumor prevalence in a clinically diverse hereditary cancer cohort

PurposeGermline variants in POT1 have been implicated in predisposition to melanoma, sarcoma, and glioma in limited studies. Here, we determine the prevalence of cancer types in individuals with POT1 pathogenic variants (PVs) undergoing multigene panel testing (MGPT) for a broad variety of cancer indications.MethodsWe performed a retrospective review of data provided on clinical documents from individuals with POT1 PVs identified via MGPT over a 5-year period. Tumor prevalence in POT1 PV heterozygotes was compared with MGPT-negative wild-type (WT) controls using χ² test.ResultsPOT1 PVs were identified in 227 individuals. POT1 PV and WT (n = 13,315) cohorts had a similar proportion of reported tumors (69.6% and 69.2%, respectively); however, POT1 PV heterozygotes were more likely to be diagnosed with multiple tumors (18.9% vs 8.7%; P < .001). Compared with POT1 WT, we identified a significant increase in melanoma (odds ratio 7.03; 95% CI 4.7-10.5; P < .001) and sarcoma (odds ratio 6.6; 95% CI 3.1-13.9; P < .001).ConclusionThis analysis of the largest POT1 PV cohort to date validates the inclusion of POT1 in hereditary cancer MGPT and has the potential to impact clinical management recommendations, particularly for patients and families at risk for melanoma and sarcoma.     

A model for self-organization of receptive fields and orientation-selective columns in the striate cortex.

In area 17 of the cat visual cortex, simple cells form a hypercolumn in which the optimum orientation from one column to the next gradually changes, composing a complete set of orientation-selective columns (orientation column). This article proposes a model for the development of the bar-shape receptive field of a simple cell and the self-organization of orientation columns. The receptive field of an immature cell in area 17 is assumed to be composed of a circular center and surrounding regions whose synaptic modification rules are different. The synaptic modifications also differ depending on whether the response of a cell is locally maximal or not. The modification of the efficacy of both excitatory and inhibitory synapses is determined according to the combination of activities of the visual cortical cell and the lateral geniculate neuron. The simulation of this model shows the development of the bar-shape receptive field and the self-organization of orientation columns of more than one cycle from 0 degrees to 180 degrees. The abnormal presentations of visual stimuli to this model result in the abnormal development of the orientation column. These simulation results are in good agreement with reported experimental results. Possible neural circuits to achieve this model are proposed. The neural circuits for the synaptic modification are built on the assumption that cortical cells release molecules to modify synaptic efficacies. The neural circuits for the detection of the maximally responding cell are composed of two kinds of inhibitory interneurons. The bar-shape receptive field is assumed to be a consequence of the topographic projection of visual afferents, radial branching of dendrites of a simple cell, and the existence of an inhibitory interneuron.     

Primary orthostatic tremor: analysis of three cases

Primary orthostatic tremor (POT) is a rare form of tremor characterized by unsteadiness and quivering of lower extremities while standing. These symptoms relieve when sitting or reclining It is much less apparent when leaning against an object or during walking. The rhythmic tremor activity with a frequency of 13-18 Hz can be obtained electromyography recordings. Here we report three cases that have typical clinical and electrophysiological findings of POT.     

Entrainment of the rat's activity rhythm by cyclic light following lateral geniculate nucleus lesions.

The rhythmic running-wheel activity of rats is entrained by sensory input via the visual system. The retinal projection transmitting visual information essential for entrainment of the activity rhythm is unknown. Lesions of the lateral geniculate nucleus (LGN) disrupt two projections, the primary optic tract (POT) and the superior accessory optic tract (AOT-SF). It was found that activity remained entrained to a light cycle following LGN lesions. This indicates that the POT and the AOT-SF are not necessary for entrainment. The two remaining projections, the retinohypothalamic pathway and the inferior accessory optic tract (AOT-IF), are sufficient to maintain entrainment. In light of other investigations, it is suggested that the retinohypothalamic pathway is the key projection for synchrony of the activity rhythm with environmental illumination. It was also found that LGN lesions severely impaired the subjects' ability to learn a brightness discrimination.