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The interplay between S-glutathionylation and phosphorylation of cardiac troponin I and myosin binding protein C in end-stage human failing hearts (2021)
Budde, Heidi ; Hassoun, Roua ; Tangos, Melina ; Zhazykbayeva, Saltanat ; Herwig, Melissa ; Varatnitskaya, Marharyta ; Sieme, Marcel ; Delalat, Simin ; Sultana, Innas ; Kolijn, Detmar ; Gömöri, Kamilla ; Jarkas, Muhammad ; Lódi, Mária ; Jaquet, Kornelia ; Kovács, Árpád ; Mannherz, Hans Georg ; Sequeira, Vasco ; Mügge, Andreas ; Leichert, Lars I. ; Sossalla, Samuel ; Hamdani, Nazha
Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca\(^{2+}\)-activated tension and Ca\(^{2+}\) sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca\(^{2+}\) sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure.
The effect of non-personalised tips on the continued use of self-monitoring mHealth applications (2020)
Unnikrishnan, Vishnu ; Schleicher, Miro ; Shah, Yash ; Jamaludeen, Noor ; Pryss, Ruediger ; Schobel, Johannes ; Kraft, Robin ; Schlee, Winfried ; Spiliopoulou, Myra
Chronic tinnitus, the perception of a phantom sound in the absence of corresponding stimulus, is a condition known to affect patients' quality of life. Recent advances in mHealth have enabled patients to maintain a ‘disease journal’ of ecologically-valid momentary assessments, improving patients' own awareness of their disease while also providing clinicians valuable data for research. In this study, we investigate the effect of non-personalised tips on patients' perception of tinnitus, and on their continued use of the application. The data collected from the study involved three groups of patients that used the app for 16 weeks. Groups A & Y were exposed to feedback from the start of the study, while group B only received tips for the second half of the study. Groups A and Y were run by different supervisors and also differed in the number of hospital visits during the study. Users of Group A and B underwent assessment at baseline, mid-study, post-study and follow-up, while users of group Y were only assessed at baseline and post-study. It is seen that the users in group B use the app for longer, and also more often during the day. The answers of the users to the Ecological Momentary Assessments are seen to form clusters where the degree to which the tinnitus distress depends on tinnitus loudness varies. Additionally, cluster-level models were able to predict new unseen data with better accuracy than a single global model. This strengthens the argument that the discovered clusters really do reflect underlying patterns in disease expression.
Einfluss der COVID-19-Pandemie auf die Inanspruchnahme des zahnärztlichen Notdienstes – eine retrospektive Analyse im Zentrum für Zahn-, Mund- und Kiefergesundheit des Universitätsklinikums Würzburg (2022)
Hollenberger, Laura
Die COVID-19-Pandemie stellte die Gesundheitssysteme weltweit vor große Herausforderungen. Um die weitere Verbreitung von SARS-CoV-2 zu verhindern, verhängten zahlreiche Staatsregierungen einen Lockdown mit Kontakt- und Ausgangsbeschränkungen. Auch in Bayern wurde das öffentliche Leben zwischen 16. März und 26. April 2020 reguliert. Krankenhäuser und Kliniken sollten sich auf eine Notfallversorgung beschränken, um ihre Kapazitäten für SARS-CoV-2-Infizierten freizuhalten. Das ZMK reduzierte im Zuge dessen ebenfalls seinen Klinikbetrieb und setzte für sechs Wochen alle planbaren Behandlungen aus. Ziel dieser retrospektiven Studie war es, den Einfluss der COVID-19-Pandemie auf die Inanspruchnahme des Notdienstes des ZMK zu untersuchen. Hierzu wurden die Behandlungsdokumente der 1299 NotfallpatientInnen, die sich zwischen 3. Februar und 7. Juni 2020 vorstellten, analysiert. Besonderes Augenmerk lag auf PatientInnen höheren Alters und/oder mit Grunderkrankung, die anfällig für einen schweren COVID-19-Verlauf sind. Während des Lockdowns halbierte sich die Anzahl der NotfallpatientInnen des ZMK. Der Anteil der COVID-19-RisikopatientInnen änderte sich jedoch nicht signifikant. Auch hinsichtlich des Geschlechtes und der Vorerkrankungen konnten keine signifikanten Änderungen festgestellt werden. Die häufigste Diagnose im Notdienst waren unkontrollierbare Schmerzen, meist endodontischen oder parodontologischen Ursprungs, gefolgt vom Abszess und vom dentalen Trauma. Zudem stieg während des Lockdowns der Anteil der NotfallpatientInnen, die stationär aufgenommen werden mussten, um 4% an. Das pandemiebedingt ohnehin stark ausgelastete Gesundheitssystem sollte nicht zusätzlich belastet werden, insbesondere wenn im Pandemieverlauf mit einem Anstieg des zahnmedizinischen Behandlungsbedarfes zu rechnen ist. Notfälle sind frühzeitig zu behandeln, Routineuntersuchungen aufrecht zu erhalten und PatientInnen über die etablierten Hygiene- und Infektionsschutzmaßnahmen und das geringe Infektionsrisiko in zahnmedizinischen Einrichtungen aufzuklären. Ziel ist, die Mundgesundheit der PatientInnen während der Pandemie aufrecht zu erhalten und einer Verschlimmerung bestehender Erkrankungen vorzubeugen. Die frühe Phase der Pandemie und der ersten Lockdown bedeuteten keine übermäßige Mehrbelastung für das ZMK. Nach meiner Einschätzung kann eine Notfallversorgung aller PatientInnen im Pandemieverlauf oder während einer zukünftigen Pandemie mit konsequentem Hygienekonzept neben dem regulären Klinikbetrieb ermöglicht werden.
“How come you don’t call me?” Smartphone communication app usage as an indicator of loneliness and social well-being across the adult lifespan during the COVID-19 pandemic (2021)
Wetzel, Britta ; Pryss, Rüdiger ; Baumeister, Harald ; Edler, Johanna-Sophie ; Gonçalves, Ana Sofia Oliveira ; Cohrdes, Caroline
Loneliness and lack of social well-being are associated with adverse health outcomes and have increased during the COVID-19 pandemic. Smartphone communication data have been suggested to help monitor loneliness, but this requires further evidence. We investigated the informative value of smartphone communication app data for predicting subjective loneliness and social well-being in a sample of 364 participants ranging from 18 to 78 years of age (52.2% female; mean age = 42.54, SD = 13.22) derived from the CORONA HEALTH APP study from July to December 2020 in Germany. The participants experienced relatively high levels of loneliness and low social well-being during the time period characterized by the COVID-19 pandemic. Apart from positive associations with phone call use times, smartphone communication app use was associated with social well-being and loneliness only when considering the age of participants. Younger participants with higher use times tended to report less social well-being and higher loneliness, while the opposite association was found for older adults. Thus, the informative value of smartphone communication use time was rather small and became evident only in consideration of age. The results highlight the need for further investigations and the need to address several limitations in order to draw conclusions at the population level.
A search for causes of rising incidence of differentiated thyroid cancer in children and adolescents after Chernobyl and Fukushima: comparison of the clinical features and their relevance for treatment and prognosis (2021)
Drozd, Valentina ; Saenko, Vladimir ; Branovan, Daniel I. ; Brown, Kate ; Yamashita, Shunichi ; Reiners, Christoph
The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. Here, we review studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima as compared to cohorts without radiation exposure of those two countries. According to the Chernobyl data, radiation-induced DTC may be characterized by a lag time of 4–5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g., nitrate are required to quantify their combined effect on thyroid cancer risk.
Association of acculturation status with longitudinal changes in health-related quality of life — results from a cohort study of adults with Turkish origin in Germany (2021)
Krist, Lilian ; Dornquast, Christina ; Reinhold, Thomas ; Becher, Heiko ; Jöckel, Karl-Heinz ; Schmidt, Börge ; Schramm, Sara ; Icke, Katja ; Danquah, Ina ; Willich, Stefan N. ; Keil, Thomas ; Brand, Tilman
Health-related quality of life (HRQL) among migrant populations can be associated with acculturation (i.e., the process of adopting, acquiring and adjusting to a new cultural environment). Since there is a lack of longitudinal studies, we aimed to describe HRQL changes among adults of Turkish descent living in Berlin and Essen, Germany, and their association with acculturation. Participants of a population-based study were recruited in 2012–2013 and reinvited six years later to complete a questionnaire. Acculturation was assessed at baseline using the Frankfurt acculturation scale (integration, assimilation, separation and marginalization). HRQL was assessed at baseline (SF-8) and at follow-up (SF-12) resulting in a physical (PCS) and mental (MCS) sum score. Associations with acculturation and HRQL were analyzed with linear regression models using a time-by-acculturation status interaction term. In the study 330 persons were included (65% women, mean age ± standard deviation 43.3 ± 11.8 years). Over the 6 years, MCS decreased, while PCS remained stable. While cross-sectional analyses showed associations of acculturation status with both MCS and PCS, temporal changes including the time interaction term did not reveal associations of baseline acculturation status with HRQL. When investigating HRQL in acculturation, more longitudinal studies are needed to take changes in both HRQL and acculturation status into account.
Impact of cardiovascular risk factors on myocardial work-insights from the STAAB cohort study (2022)
Sahiti, Floran ; Morbach, Caroline ; Cejka, Vladimir ; Tiffe, Theresa ; Wagner, Martin ; Eichner, Felizitas A. ; Gelbrich, Götz ; Heuschmann, Peter U. ; Störk, Stefan
Myocardial work is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure-strain loops, and has been validated against invasively derived pressure-volume measurements. Myocardial work is described by its components (global constructive work [GCW], global wasted work [GWW]) and indices (global work index [GWI], global work efficiency [GWE]). Applying this innovative concept, we characterized the prevalence and severity of subclinical left ventricular compromise in the general population and estimated its association with cardiovascular (CV) risk factors. Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study we comprehensively phenotyped a representative sample of the population of Würzburg, Germany, aged 30-79 years. Indices of myocardial work were determined in 1929 individuals (49.3% female, mean age 54 ± 12 years). In multivariable analysis, hypertension was associated with a mild increase in GCW, but a profound increase in GWW, resulting in higher GWI and lower GWE. All other CV risk factors were associated with lower GCW and GWI, but not with GWW. The association of hypertension and obesity with GWI was stronger in women. We conclude that traditional CV risk factors impact selectively and gender-specifically on left ventricular myocardial performance, independent of systolic blood pressure. Quantifying active systolic and diastolic compromise by derivation of myocardial work advances our understanding of pathophysiological processes in health and cardiac disease.
Risk factors in bee and Vespula venom allergy: state of the art (2022)
Stoevesandt, Johanna ; Trautmann, Axel
Background Correct recognition of risk factors enables individualized management and treatment of venom allergic patients. Methods Systematic research and review of current literature regarding the risk of (1) severe sting-induced anaphylaxis, (2) anaphylactic adverse event during venom immunotherapy (VIT), and (3) treatment failure. Results and discussion (1) Mastocytosis is the most important risk factor for severe sting-induced anaphylaxis. Hereditary α‑tryptasemia was recently identified as a genetic predictor of severe reactions. Older age is clearly associated with an increased risk; the respective impact of defined cardiovascular comorbidities has yet to be determined. Recent data do not support an aggravation of venom-induced anaphylaxis by intake of β‑blockers or angiotensin-converting enzyme (ACE) inhibitors. A higher risk in men can be attributed to more intensive exposure to stinging insects. (2) Anaphylactic side effects of VIT are most common during the buildup phase, particularly in the course of (ultra-)rush protocols involving a high number of injections and high cumulative daily doses. They are significantly more frequent during honeybee compared to Vespula VIT. Data supporting a negative effect of mastocytosis on the tolerability of VIT are scarce. Older age and cardiovascular medication are not associated with a higher incidence of VIT-induced anaphylaxis. (3) Relapsing anaphylactic reactions to both field and challenge stings are significantly more common during and after honeybee compared to Vespula VIT. Reports of severe field-sting reactions in mastocytosis patients suggest an increased risk of treatment failure which may be overcome by higher maintenance doses and longer duration of VIT.
Psychological adjustment of children and adolescents with 22q11.2 deletion syndrome and their mothers' stress and coping — a longitudinal study (2021)
Briegel, Wolfgang ; Andritschky, Christoph
At present, there is a lack of longitudinal studies on the psychological adjustment of both children and adolescents with 22q11.2 deletion syndrome (22q11.2DS) and their primary caregivers. To fill this gap, we performed a four-year follow-up study. Mothers filled out the Child Behavior Checklist 4–18, the Social Orientation of Parents with Handicapped Children questionnaire to assess maternal stress and coping strategies, and the Freiburger Personality Inventory-Revised — subscales strain and life satisfaction. Fifty-five subjects with 22q11.2DS (26 males and 29 females; age: M = 10.79 years, SD = 3.56 years) and their biological mothers (age: M = 40.84 years, SD = 4.68 years) were included in this study. Significantly higher levels of behavior problems than in the general population and an increase in these problems, especially internalizing ones, over time could be found. In contrast, maternal stress did not change significantly over time, but mothers demonstrated increased levels of strain and reduced life satisfaction at T2. Thus, careful monitoring as well as early and adequate interventions, if indicated, should be offered to families with a child with 22q11.2DS, not only for somatic complaints but also for problems with psychological adjustment.
Assessment of human health risks posed by nano-and microplastics is currently not feasible (2020)
Brachner, Andreas ; Fragouli, Despina ; Duarte, Iola F. ; Farias, Patricia M. A. ; Dembski, Sofia ; Ghosh, Manosij ; Barisic, Ivan ; Zdzieblo, Daniela ; Vanoirbeek, Jeroen ; Schwabl, Philipp ; Neuhaus, Winfried
The exposure of humans to nano-and microplastic particles (NMPs) is an issue recognized as a potential health hazard by scientists, authorities, politics, non-governmental organizations and the general public. The concentration of NMPs in the environment is increasing concomitantly with global plastic production and the usage of plastic materials. NMPs are detectable in numerous aquatic organisms and also in human samples, therefore necessitating a risk assessment of NMPs for human health. So far, a comprehensive risk assessment of NMPs is hampered by limited availability of appropriate reference materials, analytical obstacles and a lack of definitions and standardized study designs. Most studies conducted so far used polystyrene (PS) spheres as a matter of availability, although this polymer type accounts for only about 7% of total plastic production. Differently sized particles, different concentration and incubation times, and various biological models have been used, yielding hardly comparable data sets. Crucial physico-chemical properties of NMPs such as surface (charge, polarity, chemical reactivity), supplemented additives and adsorbed chemicals have been widely excluded from studies, although in particular the surface of NMPs determines the interaction with cellular membranes. In this manuscript we give an overview about the critical parameters which should be considered when performing risk assessments of NMPs, including novel reference materials, taking into account surface modifications (e.g., reflecting weathering processes), and the possible role of NMPs as a substrate and/or carrier for (pathogenic) microbes. Moreover, we make suggestions for biological model systems to evaluate immediate toxicity, long-term effects and the potential of NMPs to cross biological barriers. We are convinced that standardized reference materials and experimental parameters along with technical innovations in (nano)-particle sampling and analytics are a prerequisite for the successful realization of conclusive human health risk assessments of NMPs.
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