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IntroductionThe functional burden of vertigo, dizziness, and balance problems (VDB) might depend on the personality traits of the patients affected. The aim of this study thus was to investigate the impact of self-efficacy, risk attitudes, and time preferences on functioning in older patients with VDB before and after treatment in a specialized tertiary care center.MethodsData for this study was obtained from the MobilE-TRA2 cohort study, conducted at a specialized tertiary care center in Germany. Patients aged 60 and older were assessed during their initial stay at the care center and 3 months later, using self-administered questionnaires. Self-efficacy was measured on a scale from 1 (very low) to 5 (very high). Health-related risk attitudes were inquired using an 11-point scale. Time preferences were measured by evaluating patients' willingness to postpone a reward in favor of a greater benefit on an 11-point Likert scale. Functioning was evaluated using the Dizziness Handicap Inventory, representing functional, emotional, and physical aspects of functional disability caused by VDB. Mixed-effects regression models were used to analyze the association between the selected personality traits and functioning over time. Interaction terms with time were incorporated for each personality trait, enabling the assessment of their influence on functioning 3 months following the initial observation period.ResultsAn overall of 337 patients (53% women, median age at baseline = 70 years) were included. Patients with higher self-efficacy (Beta = −3.82, 95%-CI [−6.56; −1.08]) and higher willingness to take risks (Beta = −1.31, 95%-CI [−2.31; −0.31]) reported better functioning during their initial visit at the care center. Self-efficacy significantly predicted functioning after 3 months for overall functioning (Beta = −4.21, 95%-CI [−6.57; −1.84]) and all three domains.ConclusionOur findings suggest that patients with high self-efficacy and high willingness to take risks may exhibit better coping mechanisms when faced with the challenges of VDB. Promoting self-efficacy may help patients to better manage the duties accompanying their treatment, leading to improved functioning. These insights may inform the development of personalized treatment aimed at reducing the functional burden of VDB in older patients.

In order to expand the knowledge of microbial ecosystems from deep-sea hydrothermal vent systems located on the Central and South-East Indian Ridge, we sampled hydrothermal fluids, massive sulfides, ambient water and sediments of six distinct vent fields. Most of these vent sites were only recently discovered in the course of the German exploration program for massive sulfide deposits and no previous studies of the respective microbial communities exist. Apart from typically vent-associated chemosynthetic members of the orders Campylobacterales, Mariprofundales, and Thiomicrospirales, high numbers of uncultured and unspecified Bacteria were identified via 16S rRNA gene analyses in hydrothermal fluid and massive sulfide samples. The sampled sediments however, were characterized by an overall lack of chemosynthetic Bacteria and the presence of high proportions of low abundant bacterial groups. The archaeal communities were generally less diverse and mostly dominated by members of Nitrosopumilales and Woesearchaeales, partly exhibiting high proportions of unassigned Archaea. Correlations with environmental parameters were primarily observed for sediment communities and for microbial species (associated with the nitrogen cycle) in samples from a recently identified vent field, which was geochemically distinct from all other sampled sites. Enrichment cultures of diffuse fluids demonstrated a great potential for hydrogen oxidation coupled to the reduction of various electron-acceptors with high abundances of Hydrogenovibrio and Sulfurimonas species. Overall, given the large number of currently uncultured and unspecified microorganisms identified in the vent communities, their respective metabolic traits, ecosystem functions and mediated biogeochemical processes have still to be resolved for estimating consequences of potential environmental disturbances by future mining activities.

Introduction Vertigo, dizziness and balance problems (VDB) as well as osteoarthritis (OA) are among the health conditions with the greatest impact on mobility and social participation in older adults. Patients with VDB and OA were shown to benefit from specialised care such as vestibular rehabilitation therapy or joint replacement. However, these effects are not permanent and seem to disappear over time. One important reason might be a decreasing adherence to therapy recommendations. Findings from behavioural economics (BE) can help to shed light on individual effects on adherence behaviour and long-term outcomes of VDB and OA.Objective Based on insights from BE concepts (ie, self-efficacy, intention, and time and risk preferences), MobilE-TRA 2 investigates the determinants of functioning and health-related quality of life (HRQoL) 3 and 12 months after discharge from total hip replacement (THR)/total knee replacement (TKR) in patients with OA and after interdisciplinary evaluation for VDB.Methods and analysis MobilE-TRA 2 is a longitudinal observational study with data collection in two specialised tertiary care centres at the university hospital in Munich, Germany between 2020 and 2023. Patients aged 60 and older presenting for their first THR/TKR or interdisciplinary evaluation of VDB at Ludwig Maximilians University (LMU) hospital will be recruited for study participation. Three and twelve months after baseline assessment, all patients will receive a follow-up questionnaire. Mixed-effect regression models will be used to examine BE concepts as determinants of adherence, HRQoL and functioning.Ethics and dissemination The study was approved by the ethics committee at the medical faculty of the LMU Munich under the number 20-727. Results will be published in scientific, peer-reviewed journals and at national and international conferences. Findings will also be disseminated via newsletters, the project website and a regional conference for representatives of local and national authorities.

Circulating CD11c+ B cells are a key phenomenon in certain types of autoimmunity but have also been described in the context of regular immune responses (i.e., infections, vaccination). Using mass cytometry to profile 46 different markers on individual immune cells, we systematically initially confirmed the presence of increased CD11c+ B cells in the blood of systemic lupus erythematosus (SLE) patients. Notably, significant differences in the expression of CD21, CD27, and CD38 became apparent between CD11c− and CD11c+ B cells. We observed direct correlation of the frequency of CD21−CD27− B cells and CD21−CD38− B cells with CD11c+ B cells, which were most pronounced in SLE compared to primary Sjögren's syndrome patients (pSS) and healthy donors (HD). Thus, CD11c+ B cells resided mainly within memory subsets and were enriched in CD27−IgD−, CD21−CD27−, and CD21−CD38− B cell phenotypes. CD11c+ B cells from all donor groups (SLE, pSS, and HD) showed enhanced CD69, Ki-67, CD45RO, CD45RA, and CD19 expression, whereas the membrane expression of CXCR5 and CD21 were diminished. Notably, SLE CD11c+ B cells showed enhanced expression of the checkpoint molecules CD86, PD1, PDL1, CD137, VISTA, and CTLA-4 compared to HD. The substantial increase of CD11c+ B cells with a CD21− phenotype co-expressing distinct activation and checkpoint markers, points to a quantitative increased alternate (extrafollicular) B cell activation route possibly related to abnormal immune regulation as seen under the striking inflammatory conditions of SLE which shows a characteristic PD-1/PD-L1 upregulation.

Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in key clinical parameters: the arterial partial pressure of oxygen, the quantity and viscosity of tracheal mucus, and neutrophilic inflammatory cells in the respiratory tracts of the severe equine asthmatic subjects. At the immunological level, an upregulation of the regulatory antiallergic and anti-inflammatory cytokine IL-10 as well as a downregulation of the proallergic IL-4 and proinflammatory IFN-γ in the respiratory tracts of the severe equine asthmatic patients were identified in the treatment groups. CD4+ T lymphocytes in the respiratory tracts of the asthmatic horses were demonstrated to downregulate the mRNA expression of Tbet and IL-8. Concentrations of matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2 were significantly decreased directly after the treatment as well as six weeks post-treatment. This innovative therapeutic concept thus opens new perspectives in the treatment of severe equine asthma and possibly also that of human asthma.

Backgound: The potential of a single progenitor cell to establish and maintain long-term protective T-cell immunity in humans is unknown. For genetic disorders disabling T-cell immunity, somatic reversion was shown to support limited T-cell development attenuating the clinical phenotype. However, the cases reported so far deteriorated over time leaving unanswered the important question of long-term activity of revertant precursors and the robustness of the resulting T-cell system. Methods: We applied TCRβ-CDR3 sequencing and mass cytometry on serial samples of a now 18 year-old SCIDX1 patient with somatic reversion to analyse the longitudinal diversification and stability of a T-cell system emerging from somatic gene rescue. Findings: We detected close to 105 individual CDR3β sequences in the patient. Blood samples of equal size contained about 10-fold fewer unique CDR3β sequences compared to healthy donors, indicating a surprisingly broad repertoire. Despite dramatic expansions and contractions of individual clonotypes representing up to 30% of the repertoire, stable diversity indices revealed that these transient clonal distortions did not cause long-term repertoire imbalance. Phenotypically, the T-cell system did not show evidence for progressive exhaustion. Combined with immunoglobulin substitution, the limited T-cell system in this patient supported an unremarkable clinical course over 18 years. Interpretation: Genetic correction in the appropriate cell type, in our patient most likely in a T-cell biased self-renewing hematopoietic progenitor, can yield a diverse T-cell system that provides long-term repertoire stability, does not show evidence for progressive exhaustion and is capable of providing protective and regulated T-cell immunity for at least two decades. Funding: DFG EH 145/9-1, DFG SCHW 432/4-1 and the German Research Foundation under Germany's Excellence Strategy–EXC-2189–Project ID: 390939984.

Abstract Introduction New therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T‐regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T‐helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle‐CpG formulation (CpG‐GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a model for human asthma. Methods Twenty equine asthma‐affected horses were treated either with CpG‐GNP alone or CpG‐GNP with allergens. Two specific allergens were selected for each horse based on history and an in‐vitro test. Each horse received seven administrations of the respective nebulized composition and was examined before treatment, immediately after and 6 weeks after the treatment course. Results Clinical parameters such as breathing rate, indirect interpleural measurement, arterial blood gases, amount of tracheal mucus and percentage of neutrophils and cytokines in tracheal washes and serum samples were evaluated. Treatment with CpG‐GNP alone as well as in combinations with relevant allergens resulted in clinical improvement of nasal discharge, breathing rate, amount of secretion and viscosity, neutrophil percentage and partial oxygen pressure directly after and 6 weeks after treatment. There were no significant differences between the two treatments in clinical parameters or local cytokine profiles in the tracheal wash fluid (IL‐10, IFN‐g, and IL‐17). IL‐4 concentrations decreased significantly in both groups. Conclusion Nonspecific CpG‐GNP‐based immunotherapy shows potential as a treatment for equine and possibly also human allergic asthma.

The start of actual breeding in male social mammals can occur long after individuals attain sexual maturity. Mainly prevented from reproduction by older and dominant males, young males often queue until strong enough to compete for favorable social positions and, in this way, to obtain access to females. However, to what extent maturing males also apply tactics to reproduce before this time is largely unknown. Therefore, the aim of the present study was to elucidate male socio-sexual development from onset of sexual maturity through first mating success until the achievement of a stable social position in a complex social environment. For this purpose, guinea pigs were used as a model system and reproductive success of males living in large mixed-sex colonies was assessed during their first year of life. As a reference, males in a mixed-sex pair situation were examined. Pair-housed males reproduced for the first time around the onset of sexual maturity whereas colony-housed males did so much later in life and with a considerably higher variance. In colonies, reproductive success was significantly affected by dominance status. Dominance itself was age-dependent, with older males having significantly higher dominance ranks than younger males. Surprisingly, both younger and older colony-housed males attained substantial reproductive success of comparable amounts. Thus, younger males reproduced irrespective of queuing and already before reaching a high social status. This mating success of maturing males was most likely achieved via several reproductive tactics which were flexibly applied with the onset of sexual maturity. The period of socio-sexual development before a stable social position is established may, therefore, be a time during which male mammals use flexible behavioral tactics to achieve reproductive success more frequently than commonly is presumed. In addition, the findings strongly indicate that high behavioral plasticity exists well beyond sexual maturity.

Actuators based on the shape memory effect have recently become more and more economically important due to the many advantages of shape memory alloys (SMAs), such as their high energy density. SMAs are usually used to control the end/maximum positions, thus the actuators always move between two positions. The repeatable control of intermediate positions has so far proven difficult, because in most cases, external sensors are necessary to determine the length of the SMA element. Additionally control strategies for SMA actuators are rather complex due to the non-linear behavior of this material. The SMA actuator presented here is able to control intermediate positions with repeatable accuracy without the need of a separate control technology. The integrated control unit is based on a mechanical principle using a shaft with a circumference groove. This groove has a height profile that turns the shafts rotation, generated by the SMA, into a translational movement. Therefore, the SMA wire generates a partial stroke at each complete activation, turning the shaft partially. With several activation cycles in a row, the stroke adds up until reaching the maximum. A further activation cycle of the wire resets the actuators stroke to its initial position. Each part of the stroke can, thereby, be controlled precisely and repeatedly within the scope of each complete cycle of the actuator. Based on an integrated ratchet, each stroke of the actuator can hold energy free.

Aim. The aim of this study was to assess the changes of markers of DNA damage by glycation and oxidation in patients with type 2 diabetes and the association with diabetic nephropathy. Methodology. DNA oxidation and glycation adducts were analysed in plasma and urine by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. DNA markers analysed were as follows: the oxidation adduct 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-OxodG) and glycation adducts of glyoxal and methylglyoxal—imidazopurinones GdG, MGdG, and N2-(1,R/S-carboxyethyl)deoxyguanosine (CEdG). Results. Plasma 8-OxodG and GdG were increased 2-fold and 6-fold, respectively, in patients with type 2 diabetes, with respect to healthy volunteers. Median urinary excretion rates of 8-OxodG, GdG, MGdG, and CEdG were increased 28-fold, 10-fold, 2-fold, and 2-fold, respectively, in patients with type 2 diabetes with respect to healthy controls. In patients with type 2 diabetes, nephropathy was associated with increased plasma 8-OxodG and increased urinary GdG and CEdG. In a multiple logistic regression model for diabetic nephropathy, diabetic nephropathy was linked to systolic blood pressure and urinary CEdG. Conclusion. DNA oxidative and glycation damage-derived nucleoside adducts are increased in plasma and urine of patients with type 2 diabetes and further increased in patients with diabetic nephropathy.

In the present paper, we study quantile risk measures and their domain. Our starting point is that, for a probability measure Q on the open unit interval and a wide class L Q of random variables, we define the quantile risk measure ϱ Q as the map that integrates the quantile function of a random variable in L Q with respect to Q. The definition of L Q ensures that ϱ Q cannot attain the value + ∞ and cannot be extended beyond L Q without losing this property. The notion of a quantile risk measure is a natural generalization of that of a spectral risk measure and provides another view of the distortion risk measures generated by a distribution function on the unit interval. In this general setting, we prove several results on quantile or spectral risk measures and their domain with special consideration of the expected shortfall. We also present a particularly short proof of the subadditivity of expected shortfall.

BACKGROUND: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). METHODOLOGY/PRINCIPAL FINDINGS: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In