A Heat‐Activated Drug‐Delivery Platform Based on Phosphatidyl‐(oligo)‐glycerol Nanocarrier for Effective Cancer Treatment

The potential of cancer drugs is not fully exploited due to low tumor uptake and occurrence of systemic side effects, limiting maximum tolerated dose. Actively targeted nanocarriers improve efficacy while minimizing off‐target toxicity. Herein, it is the first time a drug‐delivery platform for heat‐triggered intravascular drug release is described, based on synthetic phosphatidyl‐(oligo)‐glycerols from organic synthesis to preclinical investigation in feline patients. For the nanocarrier formulated doxorubicin (DOX), superior tumor drug delivery and antitumor activity compared with free DOX, conventional liposomal DOX (Caelyx), and temperature‐sensitive lysolipid‐containing DOX‐liposomes in rat sarcoma are demonstrated. In a comparative oncological study with neoadjuvant treatment of feline sarcoma, a metabolic response determined with 18 F‐FDG‐positron emission tomography/magnetic resonance imaging (PET/MRI) and histopathological response after tumor resection are significantly better compared with free DOX, potentially by overcoming drug resistance based on improved intratumoral drug distribution. This novel drug‐delivery platform has great potential for the treatment of locally advanced tumors in humans

The impact of mindfulness on the wellbeing and performance of educators: A systematic review of the empirical literature

Given the potentially demanding nature of teaching, efforts are underway to develop practices that can improve the wellbeing of educators, including interventions based on mindfulness meditation. We performed systematic review of empirical studies featuring analyses of mindfulness in teaching contexts. Databases were reviewed from the start of records to January 2016. Eligibility criteria included empirical analyses of mindfulness and wellbeing outcomes acquired in relation to practice. A total of 19 papers met the eligibility criteria and were included in the systematic review, consisting of a total 1,981 participants. Studies were principally examined for outcomes such as burnout, anxiety, depression and stress, as well as more positive wellbeing measures (e.g., life satisfaction). The systematic review revealed that mindfulness was generally associated with positive outcomes in relation to most measures. However, the quality of the studies was inconsistent, and so further research is needed, particularly involving high-quality randomised control trials

Ensayo: Orientación de derecha extermista y violencia juvenil en el contexto de investigación biográfica basada en la psicología

Michaela KÖTTIGs Buch schließt zwei Lücken der bisherigen Rechtsextremismusforschung. Sie beschäftigt sich 1. mit rechtsextrem orientierten Mädchen, die in der Forschung wenig Beachtung fanden bzw. als Mitläuferinnen ohne eigene Handlungsmotivationen dargestellt wurden, und arbeitet 2. durchgängig mit qualitativen Verfahren der Biografieforschung, genauer: mit narrativ-biografischen Interviews und Fallrekonstruktionen. Dabei wird auch die dreigenerationale Familiengeschichte berücksichtigt, das Feld der Psychotraumatologie mit einbezogen und bis in den Erfahrungsraum der frühesten Kindheit zurückgeblickt. Der kontrastive Vergleich der Fallstudien zeigt verschiedene Übereinstimmungen und Varianzen in den Erfahrungsdimensionen der Interviewten, die in der jeweiligen Lebensgeschichte und den gewählten Formen der Lebensbewältigung zum Tragen kommen. Rekurrent wiederkehrende Befunde dabei sind: desolate Beziehungserfahrungen mit den Eltern, die starke Bedeutung mindestens eines Großelternteils und Reflexe der unbewussten transgenerationellen Übertragungen von Affekt- und Gedankenmustern infolge von (De-) Thematisierung der Familienvergangenheit im Dritten Reich seitens der Eltern und Großeltern. In ihrem je unterschiedlichen Zusammenwirken erweisen sich diese und andere Faktoren als spezifisch ausschlaggebend für die Herausbildung von rechtsextremen Handlungs- und Orientierungsmustern. Die erkenntnisreiche Arbeit macht deutlich, wie wichtig Forschung mit qualitativ-biografischen Verfahren in diesem Sozialbereich ist, um ein angemessen komplexes Bild der Bedingungsfaktoren rechtsextremer Biografieverläufe zu gewinnen. URN: urn:nbn:de:0114-fqs080281Michaela KÖTTIG's book closes two gaps in research on right-wing political extremism. First, she deals with young women in the right-wing scene. This is a group that has been subject to little research, having generally been taken to be on the fringe of activity and with little political activity of its own. Second, KÖTTIG works exclusively with qualitative research methods, using narrative biographical interviews and reconstructive case studies which include three-generational family histories. KÖTTIG also draws on studies of clinical psychological trauma studies and attempts to reconstruct early childhood experiences. The comparison of case studies shows numerous correspondences and variations in the biographical experience of the interviewees as well as in the consequences for individual coping mechanisms. Recurrent issues include experiences of alienation from parents, the eminent importance of one grandparent, and the effects of unconscious trans-generational transmission of affect and thought patterns caused by parents' and grandparents' suppression of the family's history during the Third Reich. These and other factors can contribute to the build-up of extreme right-wing patterns of thought and behavior. KÖTTIG's insightful study shows the importance of this kind of qualitative biographical research in examining the complexity of the biographical conditions for right-wing extremism in girls and young women. URN: urn:nbn:de:0114-fqs080281El libro de Michaela KÖTTIG cierra dos faltas en la investigación sobre extermismo de la derecha. Primero analiza mujeres jóvenes en la escena de derecha. Éste es un grupo que se ha investigado muy poco ya que ha sido visto como algo al margen de actividad y con poca actividad politica por si misma. Segundo, KÖTTIG trabaja exclusivamente con métodos cualitativos usando entrevistas biográficas narrativas y estudios de caso reconstructivos que incluyen historias de familia de tres generaciones. KÖTTIG también se refiere a estudios de traumas psicológicos y trata de reconstruir experiencias de la infancia temprana. La comparación de estudios de caso demuestra numerosas correspondencias y variaciones de las entrevistadas y tambien acerca las consecuencias para mecanismos individuales de enfrentamiento. Temas recurrentes incluyen experiencias de alienación de los padres, la importancia eminente de uno de los abuelos, y los efectos de transmisión trans-generacional inconsciente de modelos de afecto y pensamiento causados por la supresión de la historia familiar durante el "Tercer Reich" por padres y abuelos.Estos y otros factores pueden contribuir al desarollo de modelos de pensamiento y comportamiento de extrema derecha. El brillante estudio de KÖTTIG demuestra la importancia de esta forma de investigación cualitativa biográfica al examinar la complejidad de las condiciones biográficas del extremismo de derecha en chicas y mujeres jóvenes. URN: urn:nbn:de:0114-fqs08028

Review Essay: Rechtsextremismus und Jugendgewalt im Kontext psychologisch fundierter Biografieforschung

Michaela KÖTTIGs Buch schließt zwei Lücken der bisherigen Rechtsextremismusforschung. Sie beschäftigt sich 1. mit rechtsextrem orientierten Mädchen, die in der Forschung wenig Beachtung fanden bzw. als Mitläuferinnen ohne eigene Handlungsmotivationen dargestellt wurden, und arbeitet 2. durchgängig mit qualitativen Verfahren der Biografieforschung, genauer: mit narrativ-biografischen Interviews und Fallrekonstruktionen. Dabei wird auch die dreigenerationale Familiengeschichte berücksichtigt, das Feld der Psychotraumatologie mit einbezogen und bis in den Erfahrungsraum der frühesten Kindheit zurückgeblickt. Der kontrastive Vergleich der Fallstudien zeigt verschiedene Übereinstimmungen und Varianzen in den Erfahrungsdimensionen der Interviewten, die in der jeweiligen Lebensgeschichte und den gewählten Formen der Lebensbewältigung zum Tragen kommen. Rekurrent wiederkehrende Befunde dabei sind: desolate Beziehungserfahrungen mit den Eltern, die starke Bedeutung mindestens eines Großelternteils und Reflexe der unbewussten transgenerationellen Übertragungen von Affekt- und Gedankenmustern infolge von (De-) Thematisierung der Familienvergangenheit im Dritten Reich seitens der Eltern und Großeltern. In ihrem je unterschiedlichen Zusammenwirken erweisen sich diese und andere Faktoren als spezifisch ausschlaggebend für die Herausbildung von rechtsextremen Handlungs- und Orientierungsmustern. Die erkenntnisreiche Arbeit macht deutlich, wie wichtig Forschung mit qualitativ-biografischen Verfahren in diesem Sozialbereich ist, um ein angemessen komplexes Bild der Bedingungsfaktoren rechtsextremer Biografieverläufe zu gewinnen.Michaela KÖTTIG's book closes two gaps in research on right-wing political extremism. First, she deals with young women in the right-wing scene. This is a group that has been subject to little research, having generally been taken to be on the fringe of activity and with little political activity of its own. Second, KÖTTIG works exclusively with qualitative research methods, using narrative biographical interviews and reconstructive case studies which include three-generational family histories. KÖTTIG also draws on studies of clinical psychological trauma studies and attempts to reconstruct early childhood experiences. The comparison of case studies shows numerous correspondences and variations in the biographical experience of the interviewees as well as in the consequences for individual coping mechanisms. Recurrent issues include experiences of alienation from parents, the eminent importance of one grandparent, and the effects of unconscious trans-generational transmission of affect and thought patterns caused by parents' and grandparents' suppression of the family's history during the Third Reich. These and other factors can contribute to the build-up of extreme right-wing patterns of thought and behavior. KÖTTIG's insightful study shows the importance of this kind of qualitative biographical research in examining the complexity of the biographical conditions for right-wing extremism in girls and young women.El libro de Michaela KÖTTIG cierra dos faltas en la investigación sobre extermismo de la derecha. Primero analiza mujeres jóvenes en la escena de derecha. Éste es un grupo que se ha investigado muy poco ya que ha sido visto como algo al margen de actividad y con poca actividad politica por si misma. Segundo, KÖTTIG trabaja exclusivamente con métodos cualitativos usando entrevistas biográficas narrativas y estudios de caso reconstructivos que incluyen historias de familia de tres generaciones. KÖTTIG también se refiere a estudios de traumas psicológicos y trata de reconstruir experiencias de la infancia temprana. La comparación de estudios de caso demuestra numerosas correspondencias y variaciones de las entrevistadas y tambien acerca las consecuencias para mecanismos individuales de enfrentamiento. Temas recurrentes incluyen experiencias de alienación de los padres, la importancia eminente de uno de los abuelos, y los efectos de transmisión trans-generacional inconsciente de modelos de afecto y pensamiento causados por la supresión de la historia familiar durante el "Tercer Reich" por padres y abuelos.Estos y otros factores pueden contribuir al desarollo de modelos de pensamiento y comportamiento de extrema derecha. El brillante estudio de KÖTTIG demuestra la importancia de esta forma de investigación cualitativa biográfica al examinar la complejidad de las condiciones biográficas del extremismo de derecha en chicas y mujeres jóvenes

Review Essay: Extremist Right-Wing Orientation and Youth Violence in the Context of Psychologically based Biography Research

Michaela KÖTTIG's book closes two gaps in research on right-wing political extremism. First, she deals with young women in the right-wing scene. This is a group that has been subject to little research, having generally been taken to be on the fringe of activity and with little political activity of its own. Second, KÖTTIG works exclusively with qualitative research methods, using narrative biographical interviews and reconstructive case studies which include three-generational family histories. KÖTTIG also draws on studies of clinical psychological trauma studies and attempts to reconstruct early childhood experiences. The comparison of case studies shows numerous correspondences and variations in the biographical experience of the interviewees as well as in the consequences for individual coping mechanisms. Recurrent issues include experiences of alienation from parents, the eminent importance of one grandparent, and the effects of unconscious trans-generational transmission of affect and thought patterns caused by parents' and grandparents' suppression of the family's history during the Third Reich. These and other factors can contribute to the build-up of extreme right-wing patterns of thought and behavior. KÖTTIG's insightful study shows the importance of this kind of qualitative biographical research in examining the complexity of the biographical conditions for right-wing extremism in girls and young women. URN: urn:nbn:de:0114-fqs08028

Performance of Genomic Bordering Elements at Predefined Genomic Loci

Eukaryotic DNA is organized into chromatin domains that regulate gene expression and chromosome behavior. Insulators and/or scaffold-matrix attachment regions (S/MARs) mark the boundaries of these chromatin domains where they delimit enhancing and silencing effects from the outside. By recombinase-mediated cassette exchange (RMCE), we were able to compare these two types of bordering elements at a number of predefined genomic loci. Flanking an expression vector with either S/MARs or two copies of the non-S/MAR chicken hypersensitive site 4 insulator demonstrates that while these borders confer related expression characteristics at most loci, their effect on chromatin organization is clearly distinct. Our results suggest that the activity of bordering elements is most pronounced for the abundant class of loci with a low but negligible expression potential in the case of highly expressed sites. By the RMCE procedure, we demonstrate that expression parameters are not due to a potential targeting action of bordering elements, in the sense that a linked transgene is directed into a special class of loci. Instead, we can relate the observed transcriptional augmentation phenomena to their function as genomic insulators

Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib

Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G0/G1-phase arrest with decreased S/G2 fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare these in vitro findings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (n=99 patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients

Validating a minipig model of reversible cerebral demyelination using human diagnostic modalities and electron microscopy

Background Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges. Methods We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, C-11-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients. Findings We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g -ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data. Interpretation We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination