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Identifying crosstalk genetic biomarkers linking a neurodegenerative disease, Parkinson’s disease, and periodontitis using integrated bioinformatics analyses
No full textThe need of rebubbling in case of small graft detachments after Descemet Membrane Endothelial Keratoplasty (DMEK)
No full textPurpose: To investigate the need of rebubbling for small graft detachments after Descemet Membrane Endothelial Keratoplasty (DMEK).
Methods: In this retrospective study we evaluated 111 eyes from 111 patients that showed graft detachment after DMEK surgery and have achieved graft adherence by injection of air or 20% sulfur hexafluoride (SF6) to the anterior chamber (rebubbling group; n = 57) or by spontaneous adherence without intervention (control group; n = 54) at final examination. Subgroups in terms of the maximum height and in terms of the detachment area in relation to graft area were formed. Outcome measures were the increase in best-corrected visual acuity (BCVA) and the decrease in central corneal thickness (CCT) from the measurement before DMEK to six months after surgery and postoperative endothelial cell density.
Results: BCVA increased in the rebubbling group and the control group, the difference being 0.22 logMAR, p = 0.048. For eyes with a maximum height less than 500 µm, the increase of BCVA was 0.39 ± 0,36 logMAR in the control group and 0.62 ± 0,53 logMAR in the rebubbling group, p = 0.045. There was no difference of statistical significance of BCVA between both groups regarding the detachment area of less than 20% in relation to graft area. The mean decrease in CCT and postoperative endothelial cell density showed no significant difference between the rebubbling group and the control group.
Conclusion: Compared to spontaneous graft adherence, a rebubbling shows no beneficial effect on the clinical outcome for small detached DMEK grafts. Rebubbling does not decrease postoperative endothelial cell density
Crosscurrents: Welfare
No full textIn this crosscurrent contribution, we approach the notion of welfare through the lens
of the data welfare state. We, further, suggest that datafied welfare can be fruitfully
studied with the capabilities approach to better understand how ideas and values of
data welfare intersect with and may allow for the ‘good’ life and human flourishing. The
main aim is to highlight the deep-seated changes of the welfare state that emerge with
the delegation of care and control tasks to algorithmic systems and the automation
based on datafication practices. Welfare provision is undergoing major shifts that imply
fundamentally rethinking the role of technology that supports and enhances welfare
with the help of data
VARIABILITY, RESOURCE DYNAMICS, AND THE HUMAN LIFE CYCLE
No full textThe female human life cycle consists of a reproductive career nested between
juvenile and post–reproductive periods. Within these boundaries, humans exhibit
high variability of life history traits within populations (e.g., life expectancy differs
by a factor of 2 and the reproductive output by a factor of 5). The main evolution-
ary mechanisms behind such differences are the trade–offs in resource allocation
towards survival, reproduction, and development. However, empirical and theoret-
ical work have yet to explain how differences in resource availability and acquisition
influence the diversity of life cycles observed in human populations. The present
thesis focuses on understanding how the variability of resource availability and ac-
quisition shape the demographic variability within human populations. First, an
empirical analysis is presented about the relationship between the material wealth
available and age at first birth in Pimbwe women from Tanzania. Results show that
women tend to delay their first birth when they have more material wealth avail-
able but accelerate their reproductive onset when they experience higher variability.
These results support claims from life history trade offs, such as “(extra) somatic ver-
sus reproductive effort' and “current versus future reproduction'. However, they
also highlight the lack of understanding of how resources are acquired. Therefore,
a theoretical framework is developed to address how the variability of individual
resource acquisition, through production and/or transfers, influences the distribu-
tion of life history traits. For this, an agent-based model is designed, where indi-
viduals experience stochastic resource production and resource transfers governed
by a stage–structured stochastic blockmodel. Resource allocation towards survival,
reproduction, and development is deterministic. This model helps elucidate how
resource production and transfers relate to life history traits while remaining agnos-
tic to other factors (e.g. kinship, social status), allowing to further understand the
relationship between the variability in resource acquisition and demographic diver-
sity. The results indicate that the greatest variability in longevity, lifetime reproduc-
tive output, and age at first birth occurs in contexts where resource transfers are
involved. As individual probabilities of resource production increased, the variabil-
ity in both longevity and lifetime reproductive output also rose, while the variability
in age at first birth remained unchanged. In contrast, the variability of life history
traits associated with resource transfers exhibited fluctuations without a consistent
pattern. Moreover, the inclusion of resource transfers resulted in individuals liv-
ing longer, producing fewer offspring, and displaying a broader range of ages at
first birth. These results align with the idea that resource transfers have a buffering
effect against environmental uncertainty, allowing more similar life cycles by the re-
distribution of resource within the population. In conclusion, this thesis addresses
the complexity of how resource variability, either its availability or acquisition, in-
fluences the female human life cycle, and provides insights into the mechanisms
driving the demographic diversity within human populations
Ion-Implanted Amorphous Titania Nanotube Arrays - Tailoring Morphology, Chemical Composition and Electrical Conductivity for Advanced Biomedical Implants
No full textTitania nanotubes arrays represent a highly biocompatible material with an enormous surface area. Their tunable surface characteristics, especially tube diameters, enable the long-term culture of sensitive adult mammalian tissues ex vivo. Cultured murine brain slices survive for up to 14 days without showing significant degenerative effects. In fact, histomorphology and physiology of the tissues remain intact, as the native structure of the tissue is not destroyed, and physiological niches are preserved. However, increasing the conductivity of the intrinsically insulating arrays might benefit the culture of electrically excitable tissues. Moreover, conductive titania nanotube arrays might pave the way toward manufacturing advanced brain electrodes that ensure long-term neuronal tissue adhesion and stimulation. The presented thesis describes the effects of carbon ion implantation in amorphous titania nanotubes, which is carried out at room temperature to retain the amorphous structure. Since carbon is already present in the chemical composition of the pristine structures, low-energy, low-fluence carbon implantation seems advantageous for preserving the unique surface topography and biocompatibility. This thesis covers experimental, analytical, and theoretical approaches to investigate implantation-related phenomena and material characteristics within five subprojects. In detail, the research is guided by the interplay of sputtering and readsorption, amorphization and crystallization, viscous material flow and thermal spikes. The first subproject addresses morphological and compositional changes that arise from carbon implantation. Experimental observations and ab-initio-based thermodynamic considerations are combined to describe the local compositional patterning. The second subproject explores pore shrinking that occurs upon implantation in an experimental, analytical and theoretical manner. Defect-induced effects are reproduced using molecular dynamics calculations. Related to irradiation-induced viscous material flow upon implantation, surface relaxation and smoothing is quantified in the third subproject. In the fourth subproject, the increase in conductivity is analyzed both locally and globally, and the depth-dependent stoichiometry is determined. In the fifth subproject, laminin protein adsorption is assessed and the overall biocompatibility is evaluated with glial cells and neurons.
In conclusion, this thesis reveals manifold phenomena arising from carbon ion implantation of amorphous titania nanotubes, creating a comprehensive understanding of the underlying physics. Physical and chemical characteristics are evaluated to lay a foundation for further applications in the biomedical field.Titandioxid-Nanoröhren-Arrays stellen ein sehr biokompatibles Material mit einer enormen Oberfläche dar. Die justierbaren Oberflächeneigenschaften ermöglichen die Langzeitkultur empfindlicher adulter Gewebe ex vivo. So können murine Hirnschnitte in Dünnschnittkultur bis zu 14 Tage in ihrer Histomorphologie und Physiologie erhalten werden. Die native Struktur des Gewebes wird dabei nicht zerstört; physiologische Nischen bleiben erhalten. Eine Erhöhung der Leitfähigkeit der grundsätzlich isolierenden Arrays könnte die Kultur elektrisch erregbarer Gewebe begünstigen und die Herstellung fortschrittlicher Hirnelektroden ermöglichen, die eine langfristige Adhäsion und Stimulation von neuronalen Geweben bieten. Die vorliegende Arbeit beschreibt die Auswirkungen der Kohlenstoffimplantation in Titandioxid-Nanoröhren. Durch Implantation von Ionen mit niedriger Energie und geringer Fluenz sollen die amorphe Phase und die einzigartige Oberflächentopographie beibehalten werden. In fünf Teilprojekten werden experimentelle, analytische und theoretische Ansätze verfolgt, um implantationsbezogene Phänomene und Materialeigenschaften zu erforschen. Dabei wird das Zusammenspiel von Sputtern und Readsorption, Amorphisierung und Kristallisation, viskosem Materialfluss und thermischen Spikes betrachtet. Das erste Teilprojekt befasst sich mit Veränderungen der Morphologie und der chemischen Zusammensetzung. Experimentelle Beobachtungen und ab-initio-basierte thermodynamische Betrachtungen werden kombiniert, um die lokale Bildung von Strukturen mit unterschiedlichen stöchiometrischen Verhältnissen zu beschreiben. Das zweite Teilprojekt behandelt auf experimenteller, analytischer und theoretischer Ebene das Schrumpfen der Poren, das bei der Implantation auftritt. Defektinduzierte Effekte werden durch Molekulardynamik-Berechnungen nachvollzogen. Es ergibt sich ein bestrahlungsinduzierter viskoser Materialfluss, der die im dritten Teilprojekt beschriebene Oberflächenentspannung und -glättung bedingt. Das vierte Teilprojekt widmet sich der Erhöhung der Leitfähigkeit, welche lokal und global analysiert wird. Zusätzlich wird tiefenabhängig die Stöchiometrie untersucht. Im fünften Teilprojekt wird die Adsorption des Proteins Laminin evaluiert und die Biokompatibilität durch Zelltests mit Gliazellen und Neuronen eingeschätzt. Letztendlich ergibt sich ein umfassendes Bild der physikalischen Zusammenhänge und Materialeigenschaften, die aus der Kohlenstoffimplantation in amorphe Titandioxid-Nanoröhren resultieren. Damit wird der Weg zur weiteren Nutzung in der Biomedizin geebnet
Generierung automatisch ausgewerteter Programmieraufgaben auf Basis von Aufgabentemplates
No full textEs existieren verschiedene Szenarien, in denen es von Nutzen sein kann, verschiedene Varianten einer Aufgabe zur Verfügung zu haben. Aufgabenvarianten können zum Beispiel genutzt werden, um Betrugsversuche in Prüfungen zu erschweren oder die Konzeptbildung von Lernenden zu unterstützen. Die Erstellung von Aufgabenvarianten per Hand ist allerdings aufwendig und erzeugt Redundanz. Dies wirkt sich negativ auf die Wartbarkeit aus. Im Kontext dieser Arbeit wurde eine domänenspezifische Sprache entwickelt, mit deren Hilfe eine Vielzahl von Aufgabenvarianten in einem einzigen Aufgabentemplate dargestellt werden kann. Weiterhin wurde ein Generator entwickelt, der auf Basis von Aufgabentemplates Varianten erzeugt. Der Fokus lag dabei auf automatisch auswertbaren Programmieraufgaben, die mit dem Coderunner-Plugin für die Lernplattform Moodle umgesetzt werden. Der Ansatz ist erweiterbar für andere Aufgabentypen. Im Ergebnis konnte die Redundanz in Verbindung mit der Erstellung von Aufgabenvarianten verringert werden. Eine Reduzierung des Erstellungsaufwands und eine Verbesserung der Wartbarkeit ist anzunehmen
Life with hairpin-like tRNAs: Evolution of the elongation factor EF-Tu1 in Romanomermis culicivorax and its adaptation to mitochondrial armless tRNAs
No full textTransfer RNAs (tRNAs) are key molecules that bridges the translation of messenger RNAs to proteins. Typically, tRNAs are extensively folded into a conserved cloverleaf secondary structure. However, a recent discovery revealed a striking deviation from this structure in the nematode Romanomermis culicivorax, where nine of its mitochondrial tRNAs were extremely reduced due to the absence of the D- and the T-arm. As a result, these tRNAs adopt an unconventional hairpin-like structure. The missing arms are known recognition elements for several tRNA-binding proteins and so, it remains unclear how such divergent tRNAs can be efficiently used by the translation machinery. One key tRNA-binding protein, the Elongation Factor Thermo-unstable (EF-Tu), is involved in transporting tRNAs to the ribosome and is known to make extensive contacts with the T-arm of canonical tRNAs. In this work, the ability of R. culicivorax mitochondrial EF-Tu1 (Rcu mt-EF-Tu1) to accept these hairpin-like tRNAs was studied in vitro.
Regarding the binding mechanism, we showed that Rcu mt-EF-Tu1 interacts with the deviating elbow of armless tRNAs through at least two independent mechanisms. The first involves a structurally adapted extension of 50 amino acids at the C-terminal end, which enhances the affinity for tRNAs lacking the T-arm. This extension folds away from the protein’s conventional domains and is predicted to recognize a region of the tRNA normally inaccessible to the protein. The second mechanism involves a single lysine residue in domain 3 of the protein, which is predicted to enhance the complex formation through electrostatic attraction. Interestingly, this residue appears to play a prominent role in the evolutionary adaptation to bizarre tRNA structures. The transition from an acidic residue, which is important for canonical tRNA binding, to a basic residue crucial for recognizing armless tRNA may represent an evolutionary pathway that allowed EF-Tu to accept these extremely deviating tRNA
Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline
No full textBackground:
While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS.
Objective:
To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project.
Methods:
An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings.
Results:
We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM).
Conclusion:
Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages
Abortion stigma among abortion seekers, healthcare professionals and the public in high-income countries: A mixed-methods systematic review protocol
No full textIntroduction Abortion is a crucial sexual and reproductive
right. However, the legal situation of pregnancy termination
is rather heterogeneous across countries and regions.
The political climate and cultural perception may result in
abortion-related stigma. This mixed-methods systematic
review protocol aims to detail the proposed methods
for assessing the current state of research on abortion
stigma in high-income countries from an abortion seeker,
healthcare provider and public perspective.
Methods and analysis Following the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis Protocols
guideline, we conducted a systematic literature search
of peer-reviewed studies from high-income countries in
relevant electronic databases: PubMed, CINHAL, PsycINFO,
LIVIVO and Cochrane Library. Qualitative, quantitative
and mixed-method studies that measured or examined
abortion-related stigma in abortion seekers, healthcare
professionals and the general public will be included.
Assessment of risk of bias, data synthesis and qualitative
meta-aggregation will be carried out.
Ethics and dissemination The results of the systematic
review will be submitted to peer-reviewed journals and
presented at relevant conferences
A Specific Pattern of Routine Cerebrospinal Fluid Parameters Might Help to Identify Cases of West Nile Virus Neuroinvasive Disease
No full textBackground: Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease.
The prompt identification of the respective virus is important to guide not only treatment but also
potential public health countermeasures. However, in about 40% of cases, no virus is identified
despite an extensive diagnostic workup. The aim of the present study was to analyze demographic,
seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their
utility for the prediction of the causative virus. Methods: Demographic data, season, and routine
CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio,
and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME. Results: In total,
156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital
in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases
were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by
enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally,
64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older,
predominantly male, showed a severe disruption of the blood–CSF–barrier, a high proportion of
neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a
multinominal logistic regression analysis, the accuracy of these CSF parameters together with age
and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology
(66.7%), VZV (61.8%), and enteroviruses (51.9%). Conclusions: Cases with WNV ME showed a
specific pattern of routine CSF parameters and demographic data that allowed for their identification
with good accuracy. These findings might help to guide the diagnostic workup in cases with viral
ME, in particular allowing the timely identification of cases with ME due to WNV