Testing of the therapist to reduce maladaptive interactional patterns: Categorizing patients' tests.

OBJECTIVE: This empirical study undertakes a categorization of the core concept of Control Mastery Theory: mostly unconscious testing of pathogenic beliefs that patients exhibit in relating to their therapist to work on their problems. The focus lays on latent meanings of manifest tests. METHOD: We qualitatively analyze transcripts of 172 psychotherapy sessions with 23 patients for sequences in which significant patient-therapist interactions occur, and systematize identified tests into thematic categories based on what tests intent to achieve (ICC = .68). Guided by theory, the analysis is attending to complexity, individuality, and the unconscious. RESULTS: Tests circle around striving for independence, deserving/self-worth, acceptance, and entitlement. Individual tests have various underlying meanings, are interrelated, and may be multidimensional. CONCLUSION: Meanings of tests must be confirmed within the psychotherapeutic process. Incorporating the treating clinician thus seems important.

Neuropsychological and Social Characteristics of a 7 Year Old Child with Hypomelanosis of Ito Followed for 11 Years.

Hypomelanosis of Ito (HI) is a neurocutaneous disorder associated with central nervous system abnormalities, including speech delay and intellectual disability. The long term neuropsychological and social characteristics of these children are unknown. Neuropsychological observations and parental reports were obtained yearly on a child with HI from ages 7 to 18 years. Serial measures of intelligence revealed stable verbal and perceptual reasoning scores with later improvements in working memory and processing speed performance. Speech articulation improved at age 12, as did the speed of right-hand finger tapping. Improved social integration occurred, but anxiety persisted throughout this developmental period.

Emotion matters: The influence of valence on episodic future thinking in young and older adults.

In young adults, valence not only alters the degree to which future events are imagined in rich episodic detail, but also how memorable these events are later on. For older adults, how valence influences episodic detail generation while imagining future events, or recalling these details at another time, remains unclear. We investigated the effect of valence on the specificity and memorability of episodic future thinking (EFT) in young and older adults. Among young and older adults, negative EFT was accompanied by less episodic detail generation relative to positive and neutral EFT. A similar reduction in episodic specificity for negative EFT was found two days later when participants recalled their previously imagined events. Notably, while older adults generated less episodically specific future thoughts relative to young adults, age did not influence the effect of valence on episodic detail generation at imagination or recollection.

More than cell dust: microparticles isolated from cerebrospinal fluid of brain injured patients are messengers carrying mRNAs, miRNAs, and proteins.

Microparticles are cell-derived, membrane-sheathed structures that are believed to shuttle proteins, mRNA, and miRNA to specific local or remote target cells. To date best described in blood, we now show that cerebrospinal fluid (CSF) contains similar structures that can deliver RNAs and proteins to target cells. These are, in particular, molecules associated with neuronal RNA granules and miRNAs known to regulate neuronal processes. Small RNA molecules constituted 50% of the shuttled ribonucleic acid. Using microarray analysis, we identified 81 mature miRNA molecules in CSF microparticles. Microparticles from brain injured patients were more abundant than in non-injured subjects and contained distinct genetic information suggesting that they play a role in the adaptive response to injury. Notably, miR-9 and miR-451 were differentially packed into CSF microparticles derived from patients versus non-injured subjects. We confirmed the transfer of genetic material from CSF microparticles to adult neuronal stem cells in vitro and a subsequent microRNA-specific repression of distinct genes. This first indication of a regulated transport of functional genetic material in human CSF may facilitate the diagnosis and analysis of cerebral modulation in an otherwise inaccessible organ.

In search of a novel target - phosphatidylserine exposed by non-apoptotic tumor cells and metastases of malignancies with poor treatment efficacy.

This study was performed in the aim to identify potential targets for the development of novel therapy to treat cancer with poor outcome or treatment efficacy. We show that the negatively charged phospholipid phosphatidylserine (PS) is exposed in the outer leaflet of their plasma membrane not only in tumor cell lines, but also in metastases and primary cultures thereof, which contrasts with a lack of PS exposure by differentiated non-tumorigenic counterparts. Studied tumor cell lines were derived from non-tumorigenic and malignant melanomas, prostate- and renal cancer, glioblastoma and a rhabdomyosarcoma. Importantly, also metastases of melanoma expose PS and there is a correlation between malignancy of melanoma cell lines from different stages of tumor progression and PS exposure. The PS exposure we found was neither of apoptotic nor of experimental artificial origin. Finally potentially malignant and non-malignant cells could be differentiated by sorting of a primary cell culture derived from a glioblastoma based on PS exposure, which has so far not been possible within one culture due to lack of a specific marker. Our data provide clear evidence that PS could serve as uniform marker of tumor cells and metastases as well as a target for novel therapeutic approaches based on e.g. PS-specific host defense derived peptides.

Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors.

Hematopoiesis is tightly controlled by transcription regulatory networks, but how and when specific transcription factors control lineage commitment are still largely unknown. Within the hematopoietic stem cell (Lin(-)Sca-1(+)c-Kit(+)) compartment these lineage-specific transcription factors are expressed at low levels but are up-regulated with the process of lineage specification. CCAAT/enhancer binding protein α (C/EBPα) represents one of these factors and is involved in myeloid development and indispensable for formation of granulocytes. To track the cellular fate of stem and progenitor cells, which express C/EBPα, we developed a mouse model expressing Cre recombinase from the Cebpa promoter and a conditional EYFP allele. We show that Cebpa/EYFP(+) cells represent a significant subset of multipotent hematopoietic progenitors, which predominantly give rise to myeloid cells in steady-state hematopoiesis. C/EBPα induced a strong myeloid gene expression signature and down-regulated E2A-induced regulators of early lymphoid development. In addition, Cebpa/EYFP(+) cells compose a fraction of early thymic progenitors with robust myeloid potential. However, Cebpa/EYFP(+) multipotent hematopoietic progenitors and early thymic progenitors retained the ability to develop into erythroid and T-lymphoid lineages, respectively. These findings support an instructive but argue against a lineage-restrictive role of C/EBPα in multipotent hematopoietic and thymic progenitors.

The role of nanoparticle size in hemocompatibility.

It is expected that nanoparticular matters will be increasingly used for industrial and medical applications. Since it is known that nanoparticles exhibit unique and potential hazardous properties due to their small size, toxicity studies, risk assessment and risk management are of great interest. We focussed on adverse effects on human blood. Processes which warrant special attention are clotting, reactions triggering inflammatory and immune responses and hemolysis. Starting with the determination of size and surface charge in different media we assessed the effect of size and surface charge on induction of coagulation, thrombocyte activation, complement activation, granulocyte activation and hemolysis. We used polystyrene particles as model because they are available in different sizes but constant surface charges. The presence of salts and of protein in the dispersion solution increased particle size and neutralized surface charge. Positively charged particles formed aggregates in buffered solution. Interference of the particles with assays based on fluorescence associated cell sorting was identified. Positive surface charge induced activation of complement. Small size caused thrombocyte and granulocyte activation, and hemolysis. A characterization of particle size and surface charge in the solutions used for the experiments appears important for interpretation of the results. The size dependency of adverse effects in human blood is not linear; negatively charged particles larger than 60 nm hydrodynamic diameter appear to be considerably less hematotoxic than smaller ones.