Verbesserung selbst bei Therapieabbruch

Mit der vorliegenden Studie erfolgten eine Überprüfung der Wirksamkeit und eine Exploration möglicher Wirkmechanismen existenzanalytischer Einzeltherapie im naturalistischen Setting. Mittels quasiexperimenteller Untersuchung wurde überprüft, inwieweit es bei Personen mit unterschiedlichen psychischen Störungen im Zuge einer existenzanalytischen Einzeltherapie zu einer Verbesserung der Lebensqualität, der existenziellen Erfülltheit und der symptomatischen Belastung kommt. Weiters wurde überprüft, ob es bei Personen, die ihre Behandlung abbrechen, ebenfalls zu einer Verbesserung in den genannten Bereichen kommt. Anhand von drei Erhebungszeitpunkten (Therapiebeginn, Therapieende, 6 Monate nach der Therapie) erfolgte ein Vergleich zwischen Personen, die ihre Therapie erfolgreich beendeten (n = 24) und Personen, die ihre Therapie aus unterschiedlichen Gründen abbrachen (n = 15). Die Behandlungen wurden von insgesamt acht existenzanalytischen Psychotherapeuten in Ausbildung unter Supervision durchgeführt. Die Ergebnisse zeigen, dass es in beiden Gruppen über die Therapie hinaus zu einer klinisch relevanten Verbesserung hinsichtlich Lebensqualität, existenzieller Erfülltheit und symptomatischer Belastung kommt. Weiters zeigt sich, dass es bei Personen die ihre Therapie erfolgreich beenden zu einer größeren Verbesserung in den genannten Bereichen kommt, als bei Personen die ihre Therapie abbrechen. Diese Ergebnisse liefern mit ihrer hohen externen Validität einen guten Beleg für die Wirksamkeit existenzanalytischer Psychotherapie. Bezüglich der Expolration möglicher Wirkfaktoren erfolgte am Ende der Therapie eine schriftliche Befragung um herauszufinden, was an der therapeutischen Beziehung, der therapeutischen Vorgehensweise und an den Rahmenbedingungen der Therapie für die Therapie als hilfreich erlebt wurde. Diesbezüglich finden sich Hinweise, dass die vier Grundmotivationen (Längle, 2008) von elementarer Bedeutung für die therapeutische Beziehung sind.The aim of this study is to investigate the effectiveness of Existential Analysis and to explore possible factors responsible for the benefits of this method. Eight psychotherapist trainees administered the treatment under professional supervision. On the basis of a quasi-experimental examination it tries to show to what extent an existential analytical individual therapy leads to an improvement of life quality, existential fulfilment and reduction of psychological distress. Furthermore the study examines, whether clients who stop their therapy would also show improvement. To compare clients who successfully complete their therapy (n = 24) to those who discontinue treatment for various reasons (n = 15), data was collected at the beginning, the end as well as 6 months after the finishing session of the therapy. In either group the results indicate a clinically relevant improvement of life quality, existential fulfilment and a reduction of psychological distress. Furthermore, the study shows that clients who successfully complete their therapy show higher levels of improvement in all dependent variables in comparison to clients who leave therapy. These results provide strong evidence for the effectiveness of Existential Analysis. Regarding the examination of possible factors responsible for the advantages of Existential Analysis, a written survey was conducted at the end of therapy. Clients were asked which individual aspects of the therapeutic bond, the therapeutic operations and the therapeutic contract they considered helpful. The outcome points to the four existential fundamental motivations, described by Längle (2008), as essential elements of therapeutic bonding

Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration

Extended-access cocaine self-administration induces a progressive intensification of cue-induced drug craving during withdrawal termed “incubation of cocaine craving”. Rats evaluated after >1 month of withdrawal (when incubation of craving is robust) display alterations in excitatory synapses onto medium spiny neurons (MSNs) of the nucleus accumbens (NAc), including elevated levels of Ca2+-permeable AMPA receptors (CP-AMPAR) and a transition from group I metabotropic glutamate receptor (mGluR) mGlu5- to mGlu1-mediated synaptic depression. It is important to further characterize the emergent form of mGlu1-mediated synaptic depression because it has been demonstrated that mGlu1 stimulation, by normalizing CP-AMPAR transmission, reduces cue-induced cocaine craving. In the present study, we conducted whole-cell patch-clamp recordings in NAc core MSNs, comparing rats that underwent >35 days of withdrawal from cocaine self-administration to control rats that had self-administered saline. Bath application of the nonselective group I mGluR agonist dihydroxyphenylglycine (DHPG) produced a transient mGlu5-mediated synaptic depression in saline controls, whereas a persistent mGlu1-mediated synaptic depression emerged in cocaine rats. This form of long-term depression (LTD) was abolished by the inclusion of dynamin inhibitory peptide (DIP) in the recording electrode, indicating that it is mediated by removal of CP-AMPARs through a dynamin-dependent endocytosis mechanism. We further showed that CP-AMPAR endocytosis is normally coupled to the PICK1-mediated insertion of Ca2+-impermeable AMPARs (CI-AMPAR). Interestingly, this coupling is not obligatory because disruption of PICK1-mediated CI-AMPAR insertion with pep2-EVKI spared mGlu1-mediated CP-AMPAR endocytosis. Collectively, these results reveal similarities but also differences from mGlu1-LTD observed in other brain regions, and further our understanding of a form of plasticity that may be targeted to reduce cue-induced craving for cocaine and methamphetamine

Heads or tails first? Evolution of fetal orientation in ichthyosaurs, with a scrutiny of the prevailing hypothesis

According to a longstanding paradigm, aquatic amniotes, including the Mesozoic marine reptile group Ichthyopterygia, give birth tail-first because head-first birth leads to increased asphyxiation risk of the fetus in the aquatic environment. Here, we draw upon published and original evidence to test two hypotheses: (1) Ichthyosaurs inherited viviparity from a terrestrial ancestor. (2) Asphyxiation risk is the main reason aquatic amniotes give birth tail-first. From the fossil evidence, we conclude that head-first birth is more prevalent in Ichthyopterygia than previously recognized and that a preference for tail-first birth likely arose in derived forms. This weakens the support for the terrestrial ancestry of viviparity in Ichthyopterygia. Our survey of extant viviparous amniotes indicates that fetal orientation at birth reflects a broad diversity of factors unrelated to aquatic vs. terrestrial habitat, further undermining the asphyxiation hypothesis. We propose that birth preference is based on parturitional mechanics or carrying efficiency rather than habitat

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction

BACKGROUND: Insulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF). METHODS: Serum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77). RESULTS: IGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E’ ratio, and NT-proBNP levels (all P ≤ 0.02). CONCLUSION: In conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement

Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while insulin resistance (IR) is a precursor of type 2 diabetes mellitus (T2DM) and independently predicts heart failure (HF). We assessed whether IR and abnormalities of the glucose metabolism are related to LVDD.</p> <p>Methods</p> <p>We included 208 patients with normal ejection fraction, 57 (27%) of whom had T2DM before inclusion. In subjects without T2DM, an oral glucose tolerance test (oGTT) was performed. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The lower limit of the top quartile of the HOMA-IR distribution (3.217) was chosen as threshold for IR. LVDD was verified according to current guidelines.</p> <p>Results</p> <p>IR was diagnosed in 38 (18%) patients without a history of diabetes. The prevalence of LVDD was 92% in subjects with IR vs. 72% in patients without IR (n = 113), respectively (p = 0.013). In the IR group, the early diastolic mitral inflow velocity (E) in relation to the early diastolic tissue Doppler velocity (averaged from the septal and lateral mitral annulus, E'av) ratio (E/E'av) was significantly higher compared to those without IR (9.8 [8.3-11.5] vs. 8.1 [6.6-11.0], p = 0.011). This finding remains significant when patients with IR and concomitant T2DM based on oGTT results were excluded (E/E'av ratio 9.8 [8.2-11.1)] in IR vs. 7.9 [6.5-10.5] in those without both IR and T2DM, p = 0.014). There were significant differences among patients with and without LVDD regarding the HOMA-IR (1.71 [1.04-3.88] vs. 1.09 [0.43-2.2], p = 0.003). The HOMA-IR was independently associated with LVDD on multivariate logistic regression analysis, a 1-unit increase in HOMA-IR value was associated with an odds ratio for prevalent LVDD of 2.1 (95% CI 1.3-3.1, p = 0.001). Furthermore, the E/E'av ratio increases along the glucose metabolism status from normal glucose metabolism (7.6 [6.2-10.1]) to impaired glucose tolerance (8.8 [7.4-11.0]) and T2DM (10.5 [8.1-13.2]), respectively (p < 0.001).</p> <p>Conclusions</p> <p>Insulin resistance is independently associated with LVDD in subjects without overt T2DM. Patients with IR and glucose metabolism disorders might represent a target population to prevent the development of HF. Screening programs for glucose metabolism disturbances should address the assessment of diastolic function and probably IR.</p

AMPA Receptor Plasticity in Accumbens Core Contributes to Incubation of Methamphetamine Craving

BACKGROUND: The incubation of cue-induced drug craving in rodents provides a model of persistent vulnerability to craving and relapse in human addicts. After prolonged withdrawal, incubated cocaine craving depends on strengthening of nucleus accumbens (NAc) core synapses through incorporation of Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (CP-AMPARs). Through metabotropic glutamate receptor 1 (mGluR1)-mediated synaptic depression, mGluR1 positive allosteric modulators remove CP-AMPARs from these synapses and thereby reduce cocaine craving. This study aimed to determine if similar plasticity accompanies incubation of methamphetamine craving. METHODS: Rats self-administered saline or methamphetamine under extended-access conditions. Cue-induced seeking tests demonstrated incubation of methamphetamine craving. After withdrawal periods ranging from 1 to \u3e40 days, rats underwent one of the following procedures: 1) whole-cell patch clamp recordings to characterize AMPAR transmission, 2) intra-NAc core injection of the CP-AMPAR antagonist 1-naphthyl acetyl spermine followed by a seeking test, or 3) systemic administration of a mGluR1 positive allosteric modulator followed by a seeking test. RESULTS: Incubation of methamphetamine craving was associated with CP-AMPAR accumulation in NAc core, and both effects were maximal after ~1 week of withdrawal. Expression of incubated craving was decreased by intra-NAc core 1-naphthyl acetyl spermine injection or systemic mGluR1 positive allosteric modulator administration. CONCLUSIONS: These results are the first to demonstrate a role for the NAc in the incubation of methamphetamine craving and describe adaptations in synaptic transmission associated with this model. They establish that incubation of craving and associated CP-AMPAR plasticity occur much more rapidly during withdrawal from methamphetamine compared with cocaine. However, a common mGluR1-based therapeutic strategy may be helpful for recovering cocaine and methamphetamine addicts

Johann Georg Scheyers, ... praktisch-ökonomische Wasserbaukunst : zum Unterricht für Beamte, Förster, Landwirthe, Müller und jeden Landmann, besonders für die welche an Flüssen und Strömen wohnen

mit einer Vorrede vom Herrn Kammerrath Suckow, ...Aus dem Vorbesitz der Naturforschenden Gesellschaft in Zürich Exemplar der ZB Züric

Heads or tails first? Evolution of fetal orientation in ichthyosaurs, with a scrutiny of the prevailing hypothesis

Abstract According to a longstanding paradigm, aquatic amniotes, including the Mesozoic marine reptile group Ichthyopterygia, give birth tail-first because head-first birth leads to increased asphyxiation risk of the fetus in the aquatic environment. Here, we draw upon published and original evidence to test two hypotheses: (1) Ichthyosaurs inherited viviparity from a terrestrial ancestor. (2) Asphyxiation risk is the main reason aquatic amniotes give birth tail-first. From the fossil evidence, we conclude that head-first birth is more prevalent in Ichthyopterygia than previously recognized and that a preference for tail-first birth likely arose in derived forms. This weakens the support for the terrestrial ancestry of viviparity in Ichthyopterygia. Our survey of extant viviparous amniotes indicates that fetal orientation at birth reflects a broad diversity of factors unrelated to aquatic vs. terrestrial habitat, further undermining the asphyxiation hypothesis. We propose that birth preference is based on parturitional mechanics or carrying efficiency rather than habitat