Prüfung einer potentiellen strahleninduzierten Nebenschilddrüsenfunktionsstörung während einer Radioiodtherapie benigner Schilddrüsenerkrankungen

Das Ziel der vorliegenden Arbeit war die Evaluation einer potentiellen Nebenschilddrüsenfunktionsstörung unter Radioiodtherapie benigner Schilddrüsenerkrankungen. Es sollte untersucht werden, ob es in der ersten Woche unter Radioiodtherapie zu einer Veränderung in der Nebenschilddrüsenfunktion kommt. In der Klinik für Nuklearmedizin des Universitätsklinikums Gießen-Marburg GmbH, Standort Marburg, wurde eine prospektive Kohortenstudie an insgesamt 105 Probanden (75 Frauen/30 Männer, mittleres Alter 60,62 ± 14,30 Jahre) mit einer Radioiodtherapie benigner Schilddrüsenerkrankungen durchgeführt. Die 105 Probanden wurden nach ihrer Schilddrüsenerkrankung in folgende Subgruppen unterteilt: unifokale Autonomie mit 23 Patienten, multifokale Autonomie mit 8 Patienten, disseminierte Autonomie mit 37 Patienten und in die Subgruppe Autoimmunthyreopathie vom Typ Basedow (ohne endokrine Orbitopathie) bzw. Morbus Basedow (mit endokriner Orbitopathie) mit 37 Patienten. Die Konzentration des intakten Parathormons im Serum wurde direkt vor Beginn der Radioiodtherapie am Aufnahmetag, am Tag 1, 3 und 5 der stationären Radioiodtherapie und bei der ambulanten Kontrolluntersuchung einen Monat nach Beginn der Radioiodtherapie bestimmt. Bei 99 von 105 Probanden kam es unter Radioiodtherapie zu einem Abfall der Parathormonkonzentration im Serum mit einem Tiefpunkt am dritten Tag der Therapie (Abfall um 15,71 ng/l bzw. 27,54%). Die mittlere Parathormonkonzentration im Serum betrug vor Beginn der Radioiodtherapie 48,99 ± 24,05 ng/l [n = 105], am Tag 1 nach Radioiodgabe 34,09 ± 16,25 ng/l [n = 100], am Tag 3 32,74 ± 14,11 ng/l [n = 97], am Tag 5 37,02 ± 21,52 ng/l [n = 54] und bei der Nachuntersuchung einen Monat nach Beginn der Radioiodtherapie 44,62 ± 20,54 ng/l [n = 91]. Die Patienten erhielten im Mittel eine Aktivität von 1341,43 ± 459,16 MBq [n = 105] und die Herddosis der Schilddrüse unter Radioiodtherapie lag im Mittel bei 422,53 ± 245,56 Gy [n = 101]. Die einfaktorielle Varianzanalyse über alle Daten bis zum Tag 3 bestätigte den Abfall der Parathormonkonzentration im Serum (p < 0,0001). Der Student t-Test für gepaarte Stichproben ergab einen statistisch signifikanten Abfall der Mittelwerte der Parathormonkonzentration vor Therapie zu den Mittelwerten am Tag 1 (p < 0,0001) und am Tag 3 (p < 0,0001) der Therapie. Die zweifaktorielle Varianzanalyse ergab keinen signifikanten Unterschied im Abfall der Parathormonkonzentration für die Verläufe der vier Subgruppen (p = 0,32). Es ließ sich keine Korrelation zwischen dem absoluten bzw. dem relativen Parathormonabfall und der Herddosis der Schilddrüse nachweisen. Die vorliegende Arbeit zeigt erstmalig in diesem Umfang, dass es schon in den ersten Tagen nach Radioiodgabe zu einem Abfall der Parathormonkonzentration im Serum kommt, höchstwahrscheinlich aufgrund einer akuten Nebenschilddrüsenfunktionsstörung. Es wird vermutet, dass diese Störung eine Folge der ionisierenden Strahlen des 131I ist

Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors.

Paclitaxel is a common chemotherapy drug associated with the development of chronic paclitaxel-induced peripheral neuropathy (PIPN). PIPN is associated with neuroinflammatory mechanisms in pre-clinical studies. Here, we evaluated for differential gene expression (DGE) in peripheral blood between breast cancer survivors with and without PIPN and for neuroinflammatory (NI) related signaling pathways and whole-transcriptome profiles from other experiments. Pathway impact analysis identified 8 perturbed NI related pathways. Expression profile analysis found 15 experiments having similar whole-transcriptome profiles of DGE related to neuroinflammation and PIPN. These findings suggest that perturbations in pathways associated with neuroinflammation are found in cancer survivors with PIPN

Cortisol response to traumatic stress to predict PTSD symptom development – a systematic review and meta-analysis of experimental studies

Background: Pre-and post-traumatic hypothalamic–pituitary–adrenal (HPA) axis markers have been studied to predict posttraumatic stress disorder (PTSD) risk, but its acute reactivity cannot be measured in real-life settings. Experimental paradigms can depict the cortisol response to stimuli that simulate traumatic events. Objective: To review experimental studies on the cortisol response to traumatic stimuli and the correlation between cortisol and PTSD symptoms. Method: Experimental, (un-)published studies in German or English from any year were eligible if they confronted non-traumatized humans with traumatic stimuli, assessed cortisol before, during or after stimulus presentation and subsequent PTSD symptoms. The literature was searched via PubMed, PubPsych, PsychINFO, PsycArticle, Web of Science, EMBASE, ProQuest and ClinicalTrials.gov up to 16th February 2021. Risk of bias was assessed with the Cortisol Assessment List. Multilevel-meta-analyses were conducted under the random effects model. The standardized mean change (dSMC) indicated the cortisol response. Coefficient r indicated the correlations between cortisol and PTSD symptoms. Results: 14 studies, investigating 1004 individuals, were included. A cortisol response was successfully induced between 21 and 40 min post-presentation onset (kobservations = 25, dSMC = 0.15 [.03; .26]). Cortisol was not associated with overall or cluster-level PTSD symptoms. On a symptom-level, higher pre-presentation onset cortisol was correlated with lower state tension (k = 8, r = −.18 [−.35; −.01]), higher state happiness (k = 8, r = −.34 [−.59; −.03], variable inverted) and lower state anger (k = 9, r = −.14 [−.26; −.01]). Higher post-presentation onset cortisol was correlated with higher state happiness (k = 16, r = −.20 [−.33; −.06]) and lower state sadness (k = 17, r = −.16 [−.25; −.05]), whereas cortisol response was positively correlated with state anxiety (k = 9, r = .16 [0.04; 0.27]). Conclusions: Experimental paradigms effectively induce a cortisol response. Higher basal cortisol, higher cortisol, as measured after traumatic stimulus presentation, and a lower cortisol response were associated with more adaptive emotional reactions. These markers did not predict longer-term PTSD symptoms

Ohnmacht versus Unternehmertum – Wirkungen von Bildungsstandards und Kompetenzorientierung auf das lernende Subjekt in der Oberstufe

In der Debatte um Kompetenzorientierung und Bildungsstandards bisher zu wenig beachtet ist die Frage nach ihren Auswirkungen auf die Selbstwahrnehmung von Lernenden und auf ihre im Kompetenzbegriff als erlernbar gedachte Fähigkeit zur Selbstmotivierung. Internalisieren sie die ihnen zugesprochene Eigenverantwortung für ihren Lernerfolg – oder ihr Scheitern? Machen sie sich zu „bildungsunternehmerischen Subjekten“, die sich wohlkalkuliert, aber ohne Interesse an Inhalten durch den Schulalltag manövrieren? Und falls ja, wie sind diese Subjekte konstituiert, und welche Konsequenzen ergeben sich für die Beratung in der Oberstufe? Anhand zweier argumentationsmusteranalytischer Rekonstruktionen von Passagen aus Interviews mit Oberstufen-Schüler*innen, die Schwierigkeiten mit dem Fach Mathematik beschreiben, werden im Beitrag zwei Varianten von Subjektivierungsweisen angesichts responsibilisierender Adressierungen dargestellt, die einige Gemeinsamkeiten aufweisen – z.B. die Internalisierung der schulischen Verrechnungslogik –, sich aber auch in zentralen Aspekten unterscheiden, indem einmal Ohnmacht, einmal Unternehmertum im Vordergrund steht. Hieraus leiten sich einige Konsequenzen für die Beratungspraxis in der Oberstufe ab

Mental health across two years of the COVID-19 pandemic: a 5-wave longitudinal study in Germany

The COVID-19 pandemic has been negatively associated with mental health. However, little is known about the temporal dynamics of mental health in the longer term of the pandemic. We aimed to investigate symptom levels and changes of depression, anxiety, posttraumatic stress, and loneliness spanning two years of the pandemic; and to examine associated risk factors. This five-wave, longitudinal online study from May 2020 to April 2022 included 636 adults (Mage = 39.5 years, SD = 16.11; 84.1% female) from the German general population who completed the international COVID-19 Mental Health Survey. Symptoms of anxiety (Generalized Anxiety Disorder-7; GAD-7), depression (Patient Health Questionnaire-9; PHQ-9), posttraumatic stress (PTSD Checklist for DSM-5; PCL-5), and loneliness (“Do you feel lonely?”) were assessed using mixed-effects models. Associations with anxiety and depressive symptoms were examined with having children, student status, financial worries, contamination fear, and loneliness. PHQ-9, GAD-7, PCL-5, and loneliness scores overall decreased throughout the two-year period of the pandemic but exhibited an increase during two national lockdowns. Controlled for significant associations with female gender and younger age, increased PHQ-9 and GAD-7 scores were associated with contamination fear, financial worries, and loneliness. No associations were found with having children and student status. Symptoms of depression, anxiety, posttraumatic stress, and loneliness decreased over time but varied along with the dynamics of the pandemic. Longitudinal monitoring of mental health in vulnerable subgroups is required, especially those of younger age, females, and the financially insecure

Mental health across two years of the COVID-19 pandemic: a 5-wave longitudinal study in Germany

The COVID-19 pandemic has been negatively associated with mental health. However, little is known about the temporal dynamics of mental health in the longer term of the pandemic. We aimed to investigate symptom levels and changes of depression, anxiety, posttraumatic stress, and loneliness spanning two years of the pandemic; and to examine associated risk factors. This five-wave, longitudinal online study from May 2020 to April 2022 included 636 adults (Mage = 39.5 years, SD = 16.11; 84.1% female) from the German general population who completed the international COVID-19 Mental Health Survey. Symptoms of anxiety (Generalized Anxiety Disorder-7; GAD-7), depression (Patient Health Questionnaire-9; PHQ-9), posttraumatic stress (PTSD Checklist for DSM-5; PCL-5), and loneliness (“Do you feel lonely?”) were assessed using mixed-effects models. Associations with anxiety and depressive symptoms were examined with having children, student status, financial worries, contamination fear, and loneliness. PHQ-9, GAD-7, PCL-5, and loneliness scores overall decreased throughout the two-year period of the pandemic but exhibited an increase during two national lockdowns. Controlled for significant associations with female gender and younger age, increased PHQ-9 and GAD-7 scores were associated with contamination fear, financial worries, and loneliness. No associations were found with having children and student status. Symptoms of depression, anxiety, posttraumatic stress, and loneliness decreased over time but varied along with the dynamics of the pandemic. Longitudinal monitoring of mental health in vulnerable subgroups is required, especially those of younger age, females, and the financially insecure

Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?

INTRODUCTION: Neonatal cardiac surgery is associated with a systemic inflammatory reaction that might compromise the reactivity of blood cells against an inflammatory stimulus. Our prospective study was aimed at testing this hypothesis. METHODS: We investigated 17 newborn infants with transposition of the great arteries undergoing arterial switch operation. Ex vivo production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), of the regulator of the acute-phase response IL-6, and of the natural anti-inflammatory cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell culture supernatant after whole blood stimulation by the endotoxin lipopolysaccharide before, 5 and 10 days after the operation. Results were analyzed with respect to postoperative morbidity. RESULTS: The ex vivo production of TNF-α and IL-6 was significantly decreased (P < 0.001 and P < 0.002, respectively), whereas ex vivo production of IL-10 tended to be lower 5 days after the operation in comparison with preoperative values (P < 0.1). Ex vivo production of all cytokines reached preoperative values 10 days after cardiac surgery. Preoperative ex vivo production of IL-6 was inversely correlated with the postoperative oxygenation index 4 hours and 24 hours after the operation (P < 0.02). In contrast, postoperative ex vivo production of cytokines did not correlate with postoperative morbidity. CONCLUSION: Our results show that cardiac surgery in newborn infants is associated with a transient but significant decrease in the ex vivo production of the pro-inflammatory cytokines TNF-α and IL-6 together with a less pronounced decrease in IL-10 production. This might indicate a transient postoperative anti-inflammatory shift of the cytokine balance in this age group. Our results suggest that higher preoperative ex vivo production of IL-6 is associated with a higher risk for postoperative pulmonary dysfunction

The use of moderate hypothermia during cardiac surgery is associated with repression of tumour necrosis factor-α via inhibition of activating protein-1: an experimental study

INTRODUCTION: The use of moderate hypothermia during experimental cardiac surgery is associated with decreased expression of tumour necrosis factor (TNF)-α in myocardium and with myocardial protection. In order to identify the cellular mechanisms that lead to that repression, we investigated the effect of hypothermia during cardiac surgery on both main signalling pathways involved in systemic inflammation, namely the nuclear factor-κB (NF-κB) and activating protein-1 pathways. METHOD: Twelve female pigs were randomly subjected to standardized cardiopulmonary bypass with moderate hypothermia or normothermia (temperature 28°C and 37°C, respectively; six pigs in each group). Myocardial probes were sampled from the right ventricle before, during and 6 hours after bypass. We detected mRNA encoding TNF-α by competitive RT-PCR and measured protein levels of TNF-α, inducible nitric oxide synthase and cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF-κB and activating protein-1, as well as phosphorylation of p38 mitogen-activated protein kinase by electrophoretic mobility shift assay with super shift and/or Western blot. RESULTS: During and after cardiac surgery, animals subjected to hypothermia exhibited lower expression of TNF-α and cyclo-oxygenase-2 but not of inducible nitric oxide synthase. This was associated with lower activation of p38 mitogen-activated protein kinase and of its downstream effector activating protein-1 in hypothermic animals. In contrast, NF-κB activity was no different between groups. CONCLUSION: These findings indicate that the repression of TNF-α associated with moderate hypothermia during cardiac surgery is associated with inhibition of the mitogen-activated protein kinase p38/activating protein-1 pathway and not with inhibition of NF-κB. The use of moderate hypothermia during cardiac surgery may mitigate the perioperative systemic inflammatory response and its complications