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Investigating neuronal correlates of Obsessive-Compulsive Disorder - novel approaches using brain stimulation and fMRI
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Einzelnukleotid-Polymorphismen des Glucocorticoid-Rezeptorgens und PTSD-Symptomatik bei Intensivpatienten nach kardiochirurgischen Eingriffen
Get PDFMobile mental health platforms and gamification
Get PDFThe growing prevalence of mental health issues, compounded by limited access to support systems, has left a significant portion of the population without adequate interventions. Various barriers, including financial constraints and geographical limitations, hinder access to traditional mental health care, particularly affecting vulnerable demographics such as teens and young adults. The COVID-19 pandemic exacerbated this issue, leading to a surge in demand for affordable and remote mental health solutions. Digital interventions, particularly mobile applications, offer a promising avenue for accessible care, aligning with the preferences and habits of younger demographics. However, while the market is flooded with such solutions, only a small fraction have undergone rigorous clinical evaluation, raising concerns about their efficacy and safety. Furthermore, studies indicate that attrition rates with digital mental health products are higher compared to traditional interventions, highlighting the challenge of sustaining engagement for effective outcomes. Efforts to address these issues are crucial to meet the pressing need for accessible and effective mental health care
Effect of prior flavivirus immunity on the adaptive response to the yellow fever 17D vaccine
Get PDFThe yellow fever 17D vaccine (YF17D) is the most effective of all flavivirus vaccines. Given the widespread prevalence of flaviviruses, YF17D is frequently administered to individuals with pre-existing cross-reactive immunity, potentially influencing immune responses. Here, I investigated the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus vaccine (TBEV) on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv).
Previous TBEV vaccination did not influence the early neutralizing response to YF17D, predominantly driven by the IgM antibody fraction. TBEV pre-vaccinated individuals, however, developed high amounts of cross-reactive IgG antibodies with limited capacity to neutralize YF17D. In contrast, TBEV-unvaccinated individuals elicited a non-crossreacting but efficiently neutralizing response. Utilizing recombinant YF17D envelope protein mutants displaying different epitopes, I identified quaternary dimeric epitopes as the main target of neutralizing antibodies and the fusion loop epitope (FLE) as the focus of cross-reactive antibodies. TBEV pre-vaccinated individuals expanded anti-FLE IgG antibodies that can cause antibody-mediated enhancement (ADE) of dengue virus infection in vitro.
Flow cytometric analysis consistently showed a greater expansion of antigen-specific memory B cells in TBEV-pre-vaccinated individuals following YF17D vaccination. Furthermore, TBEV pre-vaccinated individuals displayed a diverse antibody response, covering a wide range of specificities beyond cross-reactive epitopes shared by TBEV and YF17D. TBEV-induced antibodies enhanced YF17D vaccine immunogenicity, resulting in higher antibody titers and a more robust antigen-specific CD4 T cell response, measured in an ex vivo restimulation assay on day 28. In contrast to the significant differences in serum antibody titers, TBEV pre-vaccination had no impact on the longitudinal dynamics of bulk and tetramer-specific CD4 and bulk CD8 T cell responses, as assessed through multiparametric spectral flow cytometry. Genomic DNA bulk B cell receptor (BCR) sequencing indicated limited clonal expansion in the bulk repertoire and reduced diversity by days 7 and 14 post-vaccination, consistent with the B cell population kinetics observed through flow cytometry.
In conclusion, the YF17D vaccine elicits both humoral and cellular immune responses that culminate in the generation of protective immunity. Pre-existing TBEV immunity does not impact the timing of the cellular immune response, but it significantly boosts YF17D immunogenicity and modifies the immunodominance of YF17D epitopes. This shift redirects the response in TBEV-pre-vaccinated individuals from a finely tuned, non-cross-reactive neutralizing response to a cross-reactive response focused on the FLE, with the potential to enhance dengue virus infection
A study of the relationship between local particulate pollution and exhaled nitric oxide in children with non-allergic asthma admitted to a high-altitude rehabilitation clinic
Get PDFParticulate pollution correlates with exhaled nitric oxide (FeNO; a measure of airway inflammation) in children with asthma. Non-allergic asthma represents a very small subset of this group and has different pathophysiological mechanisms from allergic asthma. This study examined the relationship between particulate pollution and FeNO in children with non-allergic asthma admitted to a high-altitude rehabilitation clinic at 1200m in Germany. No correlation was found. I was able to identify non-allergic asthma patients with clinically raised FeNO and to show that this value normalised over the course of a high-altitude admission. As a validation of the above results, I replicated the finding that FeNO decreases significantly during high-altitude rehabilitation in allergic asthma patients.In Kindern mit Asthmaerkrankung ist ein zeitlicher Zusammenhang zwischen Feinstaubbelastung in der Luft und ausgeatmetem Stickstoffmonoxid (FeNO, ein Zeichen von Entzündungsprozessen in der Lunge) bekannt. Die Überzahl der Kinder, welche an Asthma bronchiale leiden, sind an der allergischen Form erkrankt. Nur sehr wenige Kinder leiden an nichtallergischem Asthma bronchiale. Die nichtallergische Form und die allergische Form unterscheiden sich in der Pathophysiologie. Diese Studie untersuchte das Verhältnis zwischen Feinstaubbelastung und ausgeatmetem FeNO in Kindern mit nichtallergischem Asthma, welche in einer pulmologischen Rehabilitationsklinik bei 1200 Höhenmetern aufgenommen waren. Es zeigte sich kein Verhältnis. In der Kohorte fanden sich aber Kinder mit nichtallergischem Asthma und klinisch erhöhtem FeNO. Bei diesen Kindern zeigte sich während des Klinik-Aufenthalts eine Reduktion im FeNO-Wert. Auch konnte das bereits bekannte Verhältnis zwischen verbrachter Zeit in der Höhe und reduziertem FeNO bei allergischen Patienten repliziert werden
"Rapid-Deployment"-Prothesen in bikuspider Aortenklappenmorphologie
Get PDFDie Verwendung eines operativen Aortenklappenersatzes (SAVR) mit Rapid Deployment Prothesen (RD) bei bikuspider Aortenklappenmorphologie (BAV) ist aufgrund der anulären Asymmetrie und der erheblichen Verkalkung der Klappensegel mit einer Reihe von technischen Herausforderungen verbunden. Dies gilt insbesondere für bikuspide Aortenklappen mit Sievers-Typ-0-Morphologie, die mit Vorsicht rekonstruiert werden müssen. Ziel der Studie war eine retrospektive Analyse der Umsetzbarkeit von schnell einsetzbaren Prothesen bei bikuspider Morphologie.
Von Januar 2014 bis März 2022 wurden 35 Patientinnen und Patienten mit bikuspider Aortenklappenmorphologie (15 Patientinnen und Patienten mit Sievers Typ 0 BAV und 16 mit Sievers Typ 1 BAV und 4 von unbekanntem Typ) einer RD SAVR unterzogen, dies bildete unser Hauptkollektiv. Zum gleichen Zeitpunkt erhielten 79 Personen eine RD Klappenprothese bei trikuspider Morphologie, diese wurden als Vergleichskollektiv gewählt. Die Patientinnen und Patienten in beiden Kohorten wiesen ähnliche Risikoprofile präoperativ auf, bei signifikant häufigeren Bypass- Operationen als Begleitverfahren im Vergleichs-, dafür signifikant häufigere Aortenersätze im Hauptkollektiv. Die Daten wurden retrospektiv erhoben, und die mittlere Nachbeobachtungszeit betrug 15 Monate.
In beiden Gruppen wurden vergleichbare klinische Ergebnisse beobachtet. In keiner der Gruppen traten paravalvulären Lecks auf und es waren keine erneuten valvulären Eingriffe erforderlich. Die CPB- und Cross-Clamping-Zeiten (120 ± 44,5 min BAV vs. 111 ± 38 min TAV und 72,5 ± 25 min BAV vs. 77 ± 26 min TAV) unterschieden sich nicht signifikant. Im bikuspiden Kollektiv erhielten die Personen signifikant größere Klappenprothesen (25.0 ± 2.0 mm BAV vs. 24.1 ± 1.5 mm TAV) bei vergleichbaren, sehr guten postoperativen Gradienten (ΔPmax 15,3 ± 6,4 mmHg BAV, 16,2 ± 9,5 mmHg TAV). Es wurde kein signifikanter Unterschied zwischen den Gruppen in Bezug auf die postoperative Schrittmacherindikation, postoperative Schlaganfälle oder Mortalität festgestellt.
Die Sievers-Klassifikationen wurden zusätzlich untereinander verglichen. Hierbei gibt es keine signifikanten Unterschiede bezogen auf die präoperativen Risikoprofile, sowie die Begleiteingriffe und intraoperative Zeiten (CPB 112,2 ± 40,3 min ST0 vs. 127,2 ± 48,7 min ST1, Cross-Clamping- Zeit 74,9 ± 28,5 min ST0 vs. 70,1 ± 21,4 min ST1). Die postoperativen Gradienten sind ebenfalls vergleichbar (ΔPmax 13,9 ± 5,4 mmHg ST0 vs 17,1 ± 6,7 mmHg ST1). Im Sievers Typ 0 Kollektiv zeigt sich eine Schrittmacherrate von 20%, im Gegensatz zu 6% bei ST1.
Die ringförmige Symmetrie kann durch eine präzise Prothesengröße und -platzierung entsprechend der individuellen Klappenmorphologie unabhängig von der Sievers-Klassifikation der BAV adäquat wiederhergestellt werden, indem ein anderer Orientierungspunkt für die erste Naht gewählt wird. Die RD SAVR scheint bei jeder bikuspiden Morphologie ein sicherer Ansatz mit guten hämodynamischen Ergebnissen und Zeitersparnis bei richtiger Implantationsstrategie zu sein.The use of surgical aortic valve replacement (SAVR) with rapid deployment prostheses (RD) in bicuspid aortic valve (BAV) morphology is associated with several technical challenges due to annular asymmetry and significant calcification of the valve leaflets. This is particularly true for bicuspid aortic valves with Sievers type 0 morphology, which must be reconstructed with caution. The aim of the study was to retrospectively analyse the feasibility of rapidly deployable prostheses with bicuspid morphology.
From January 2014 to March 2022, 35 patients with bicuspid aortic valve morphology (15 patients with Sievers type 0 BAV and 16 with Sievers type 1 BAV and 4 of unknown type) underwent RD SAVR, which constituted our main cohort. At the same time, 79 people underwent RD valve prosthesis for tricuspid morphology; these were selected as the comparison collective. The patients in both cohorts had similar preoperative risk profiles, with significantly more frequent bypass operations as a concomitant procedure in the comparative cohort, but significantly more frequent aortic replacements in the main cohort. Data were collected retrospectively, and the mean follow-up period was 15 months.
Comparable clinical results were observed in both groups. No paravalvular leaks occurred in either group and no repeat valvular interventions were required. The CPB and cross-clamping times (120 ± 44.5 min BAV vs. 111 ± 38 min TAV and 72.5 ± 25 min BAV vs. 77 ± 26 min TAV) did not differ significantly. In the bicuspid collective, the individuals received significantly larger valve prostheses (25.0 ± 2.0 mm BAV vs. 24.1 ± 1.5 mm TAV) with comparable, very good postopera- tive gradients (ΔPmax 15.3 ± 6.4mmHg BAV, 16.2 ± 9.5mmHg TAV). No significant difference was found between the groups in terms of postoperative pacemaker indication, postoperative strokes or mortality.
The Sievers classifications were also compared with each other. There were no significant differences regarding the preoperative risk profiles, as well as the concomitant interventions and intraoperative times (CPB 112.2 ± 40.3 min ST0 vs. 127.2 ± 48.7 min ST1, cross-clamping time 74.9 ± 28.5 min ST0 vs. 70.1 ± 21.4 min ST1). The postoperative gradients are also comparable (ΔPmax 13.9 ± 5.4 mmHg ST0 vs. 17.1 ± 6.7 mmHg ST1). The Sievers type 0 collective shows a pacing rate of 20%, in contrast to 6% in ST1.
Annular symmetry can be adequately restored by precise prosthesis sizing and placement according to the individual valve morphology, independent of the Sievers classification of BAV, by choosing a different orientation point for the first suture. RD SAVR appears to be a safe approach for any bicuspid morphology with good haemodynamic results and time savings with the correct implantation strategy