Phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension: a case report

<p>Abstract</p> <p>Background</p> <p>Portopulmonary hypertension (PPHTN) is a severe complication in liver cirrhosis. PDE5 inhibitors lower pulmonary arterial pressure (PAP) in PPHTN. However, their effect on portal hypertension has not yet been investigated.</p> <p>Case presentation</p> <p>A 55 year old male patient presented with PPHTN and alcoholic liver cirrhosis. 10 mg of Tadalafil, a PDE5 inhibitor with a long half-life, was administered orally under continuous monitoring of pulmonary and portal hemodynamics. For maintenance therapy the patient received Sildenafil 20 mg bid.</p> <p>Tadalafil lowered mean PAP from 45 to 39 mmHg within 60 minutes. Cardiac output (CO) increased from 6.8 to 7.9 l/min. Central venous pressure (CVP) remained stable at 3 mmHg. Systolic and diastolic blood pressure was lowered from 167/89 to 159/86 mmHg. Pulse rate increased from 75 to 87 per min. Wedged hepatic vein pressure (WHVP) decreased from 21 to 18 mm Hg, hepatovenous pressure gradient (HVPG) decreased from 10 to 7 mmHg. Hemodynamic monitoring after 6 months of Sildenafil therapy revealed a sustained lowering of mean PAP. HVPG remained constant at 10 mmHg. Cardiac and pulmonary performance had further improved.</p> <p>Conclusion</p> <p>This case report shows for the first time, that phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension.</p

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score (“teloscore”, which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35–1.76; p = 1.54 × 10−10) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73–0.88; p = 1.87 × 10−6, ptrend = 3.27 × 10−7). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10−9 for highest vs. lowest quintile; p = 1.82 × 10−10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer

Child temperament as a longitudinal predictor of mother-adolescent interaction quality: are effects independent of child and maternal mental health?

Adaptive parent-child interaction plays a major role in healthy child development. Caregiver mental health problems can negatively impact parent-child interaction. In turn, interactional quality is often studied as a predictor of child outcome. However, child characteristics supposedly shape parent-child interactions as well. Given associations between child and caregiver mental health and child temperament, this study aimed at differentiating their effects on dyadic interaction quality in adolescence. Child temperament and character at age 5 were investigated as longitudinal predictors of observed mother-adolescent interactional quality at age 14 in a community sample (N = 76). It was examined whether these effects were independent of maternal and child mental health and earlier dysfunctional interaction. Lower novelty seeking, higher reward dependence, and higher cooperativeness separately predicted higher dyadic interactional quality at age 14. Controlling regressions for dysfunctional interaction at age 5, which was a significant negative predictor of later interactional quality, cancelled out the effects of novelty seeking and cooperativeness. Past or concurrent maternal or child psychopathology did not explain variance in mother-adolescent interaction. Applying backward selection, a model including reward dependence and dysfunctional interaction at age 5 and concurrent maternal stress showed the best fit for explaining dyadic interaction quality. Results suggest that enduring rather than transient child features predict interactional quality in a community sample. Effects of temperament are not better explained by those of psychopathology, but a combination of child, maternal, and dyadic features predicted dyadic behaviour best. Selective prevention should target parenting in the context of challenging child characteristics specifically

Mother–child interactions in adolescents with borderline personality disorder traits and the impact of early life maltreatment

Abstract Background Early detection and intervention of borderline personality disorder (BPD) in adolescence has become a public health priority. Theoretical models emphasize the role of social interactions and transgenerational mechanisms in the development of the disorder suggesting a closer look at caregiver-child relationships. Methods The current study investigated mother-adolescent interactions and their association with adolescent BPD traits by using a case–control design. Thirty-eight adolescent patients with ≥ 3 BPD traits and their mothers (BPD-G) were investigated in contrast to 35 healthy control dyads (HC-G). Maternal, adolescent and dyadic behavior was coded using the Coding Interactive Behavior Manual (CIB) during two interactions: a fun day planning and a stress paradigm. Additional effects of maternal and/or adolescent early life maltreatment (ELM) on behavior were also explored. Results BPD-G displayed a significantly lower quality of maternal, adolescent and dyadic behavior than the HC-G during both interactions. Maternal and adolescent behavior was predicted by BPD traits alone, whilst dyadic behavior was also influenced by general adolescent psychopathology. Exploratory analyses of CIB subscales showed that whilst HC-G increased their reciprocal behavior during stress compared to the fun day planning, BPD-G dyads decreased it. Maternal ELM did not differ between groups or have any effect on behavior. Adolescent ELM was correlated with behavioral outcome variables, but did not explain behavioral outcomes above and beyond the effect of clinical status. Discussion/Conclusion Our data suggest a stronger focus on parent–child interactions in BPD-specific therapies to enhance long-term treatment outcomes in adolescent BPD patients. Further research employing study designs that allow the analyses of bidirectional transactions (e.g. longitudinal design, behavioral microcoding) is needed

Zehn Gebote der Verhaltenswissenschaften in der Pandemiebekämpfung

Das alltägliche Verhalten jeder und jedes Einzelnen spielt bei der Eindämmung der Pandemie eine große Rolle. Die Verhaltenswissenschaften können viel dazu beitragen, die Gestaltung, Kommunikation, Durchsetzung und Akzeptanz von Regeln, die unser aller Verhalten zu diesem Zweck beeinflussen wollen, zu verbessern. Im Folgenden diskutieren wir „zehn Gebote“ der Verhaltenswissenschaften in einer Pandemie. Auch wenn sie allgemein formuliert bleiben, so beziehen sie sich auf die Gestaltung (das verhaltenswissenschaftliche Design) von Massentests, die Durchführung der Schutz-Impfungen, die Corona-App, das Testen und Nachverfolgen oder die Maßnahmen zur Ansteckungsvermeidung. Diese Gebote sind natürlich kein Allheilmittel zur Bekämpfung der Pandemie, aber ohne ihre Berücksichtigung sind oft gut gemeinte, aber falsch ausgestaltete Regeln und Anwendungen weniger oder gar nicht effektiv. Im schlimmsten Fall können gut gemeinte Regeln sogar kontraproduktiv wirken

Zehn Gebote der Pandemiebekämpfung

Gastbeitrag: Das Verhalten spielt bei der Eindämmung der Pandemie eine große Rolle. Ohne dessen Berücksichtigung sind Regeln weniger effektiv

Child versus adolescent borderline personality disorder traits: Frequency, psychosocial correlates, and observed mother–child interactions.

Research has established the diagnostic validity of borderline personality disorder (BPD) in adolescence. The roots of BPD often lie in childhood; however, significantly less is known about the presence and correlates of BPD traits in school-age children and whether these are comparable with those observed in adolescents. Trained psychologists administered the Childhood Interview for Borderline Personality Disorder in a cohort of 14-year-old adolescents (n = 76) and a cohort of 9-year-old children (n = 70). We compared the prevalence of BPD traits in both cohorts and investigated common psychosocial correlates (comorbidity, impaired quality of life, emotional/behavioral problems, maternal distress, and observed mother-child interaction). Children and adolescents showed no significant differences regarding the type and frequency of BPD traits. In both cohorts, BPD traits were associated with comorbidity, emotional and behavioral problems, and lower quality of life. In contrast to adolescents, children's BPD traits were not significantly related to maternal distress and showed less relations to interaction patterns. Negative maternal and dyadic behavior were associated with more BPD traits in adolescents during a conflict discussion but not during fun day planning. Our study suggests that BPD traits in children are similarly frequent as in adolescents and accompanied by psychosocial impairment. However, age-related differences were revealed, mostly indicating weaker associations with the mother-child relationship. Mother-child interaction patterns in youth seem to be especially relevant during conflict discussion and provide a target for intervention. Our study provides preliminary support for potential early detection of BPD pathology among children and encourages further study of its life span perspective

Child Versus Adolescent Borderline Personality Disorder Traits: Frequency, Psychosocial Correlates, and Observed Mother-Child Interactions

Research has established the diagnostic validity of borderline personality disorder (BPD) in adolescence. The roots of BPD often lie in childhood; however, significantly less is known about the presence and correlates of BPD traits in school-age children and whether these are comparable with those observed in adolescents. Trained psychologists administered the Childhood Interview for Borderline Personality Disorder in a cohort of 14-year-old adolescents (n = 76) and a cohort of 9-year-old children (n = 70). We compared the prevalence of BPD traits in both cohorts and investigated common psychosocial correlates (comorbidity, impaired quality of life, emotional/behavioral problems, maternal distress, and observed mother-child interaction). Children and adolescents showed no significant differences regarding the type and frequency of BPD traits. In both cohorts, BPD traits were associated with comorbidity, emotional and behavioral problems, and lower quality of life. In contrast to adolescents, children's BPD traits were not significantly related to maternal distress and showed less relations to interaction patterns. Negative maternal and dyadic behavior were associated with more BPD traits in adolescents during a conflict discussion but not during fun day planning. Our study suggests that BPD traits in children are similarly frequent as in adolescents and accompanied by psychosocial impairment. However, age-related differences were revealed, mostly indicating weaker associations with the mother-child relationship. Mother-child interaction patterns in youth seem to be especially relevant during conflict discussion and provide a target for intervention. Our study provides preliminary support for potential early detection of BPD pathology among children and encourages further study of its life span perspective

Influence of Short and Long Hyperglycemia on Cardioprotection by Remote Ischemic Preconditioning&mdash;A Translational Approach

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 &plusmn; 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 &plusmn; 4% (p &lt; 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 &plusmn; 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 &plusmn; 4% (p &lt; 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p &lt; 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 &plusmn; 7%; p &lt; 0.05 vs. HGl Con; HGl Con 59 &plusmn; 5%)

Influence of Short and Long Hyperglycemia on Cardioprotection by Remote Ischemic Preconditioning—A Translational Approach

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%)