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Publisher
- Springer Nature (112) (remove)
Purpose
The significance of the underlying literature in clinical guidelines can be weakened by the risk of bias, which could negatively affect the recommendations. Especially in controversial matters, such as fluoride use for caries prevention in children, biased results may be not reliable and lead to incorrect conclusions. This study was performed to detect bias in underlying literature of the German guideline for caries prevention using fluoride in children, where no consensus was reached between paediatricians and paediatric dentists.
Methods
Three tools used for risk of bias assessments of different study designs were RoB 2 for RCTs, ROBINS-I for non-randomized studies, and ROBIS for systematic reviews. For each study cited in the guideline two independent risk of bias assessments were performed. Disagreements were resolved by consensus.
Results
Out of 58 papers, 48.3% (n = 28) showed high risk of bias, with the majority in sections regarding fluoride tablets, fluoridated toothpaste, and paediatricians’ recommendations. 9 out of 20 recommendations and statements were based on studies with high risk of bias, all of which were in these three controversial sections. 13 out of 29 RCTs showed high risk of bias (44.8%), as all 13 non-randomized trials did, while only 2 of 16 (12.5%) systematic reviews had high risk of bias.
Conclusion
Considering risk of bias of cited studies in clinical guidelines may result in substantial changes in its recommendations and aid in reaching consensus. Efforts should be made to assess risk of bias of underlying literature in future clinical guidelines.
Background
Microvascular decompression (MVD) success rates exceed 90% in hemifacial spasm (HFS). However, postoperative recovery patterns and durations are variable.
Objective
We aim to study factors that might influence the postoperative patterns and duration needed until final recovery.
Method
Only patients following de-novo MVD with a minimum follow-up of 6 months were included. Overall trend of recovery was modeled. Patients were grouped according to recognizable clinical recovery patterns. Uni- and multivariable analyses were used to identify the factors affecting allocation to the identified patterns and time needed to final recovery.
Results
A total of 323 (92.6%) patients had > 90% symptom improvement, and 269 (77.1%) patients had complete resolution at the last follow-up. The overall trend of recovery showed steep remission within the first 6 months, followed by relapse peaking around 8 months with a second remission ~ 16 months. Five main recovery patterns were identified.
Pattern analysis showed that evident proximal indentation of the facial nerve at root exit zone (REZ), males and facial palsy are associated with earlier recovery at multivariable and univariable levels. anterior inferior cerebellar artery (AICA), AICA/vertebral artery compressions and shorter disease durations are related to immediate resolution of the symptoms only on the univariable level. Time analysis showed that proximal indentation (vs. distal indentation), males and facial palsy witnessed significantly earlier recoveries.
Conclusion
Our main finding is that in contrast to peripheral indentation, proximal indentation of the facial nerve at REZ is associated with earlier recovery. Postoperative facial palsy and AICA compressions are associated with earlier recoveries. We recommend a minimum of 1 year before evaluating the final outcome of MVD for HFS.
Purpose
Despite being rarely reported, ischemic insults resulting from compromising small brainstem perforators following microvascular decompression (MVD) remain a potential devastating complication. To avoid this complication, we have been using indocyanine green (ICG) angiography intraoperatively to check the flow within the small brainstem perforators. We aim to evaluate the safety and usefulness of ICG videoangiography in MVD.
Methods
We extracted retrospective data of patients who received ICG videoangiography from our prospectively maintained database for microvascular decompression. We noted relevant data including demographics, offending vessels, operative technique, outcome, and complications.
Results
Out of the 438 patients, 15 patients with a mean age (SD) of 53 ± 10.5 years underwent intraoperative ICG angiography. Male:female was 1:1.14. The mean disease duration prior to surgery was 7.7 ± 5.3 years. The mean follow-up (SD) was 50.7 ± 42.0 months. In 14 patients, the offending vessel was an artery, and in one patient, a vein. Intraoperative readjustment of the Teflon pledget or sling was required in 20% (3/15) of the cases. No patient had any sort of brainstem ischemia. Eighty percent of the patients (12/15) experienced complete resolution of the spasms. 86.7% (13/15) of the patients reported a satisfactory outcome with marked improvement of the spasms. Three patients experienced slight hearing affection after surgery, which improved in two patients later. There was no facial or lower cranial nerve affection.
Conclusion
Intraoperative ICG is a safe tool for evaluating the flow within the brain stem perforators and avoiding brainstem ischemia in MVD for hemifacial spasm.
To a large extent health-related quality of life (HRQoL) is a product of life-course experiences. Therefore, we examined employment, marital, and reproductive life-course typologies as predictors of HRQoL in women and men. To determine life course clusters, sequence and cluster analysis were performed on the annual (waves 1990–2019) employment, marital, and children in household states of the German Socio-Economic Panel data (N = 8,998; age = 53.57, 52.52% female); separately for men and women. Using hierarchical linear regression analyses, and Tukey HSD post-hoc tests, associations between clusters and change in life satisfaction, subjective mental, and physical health were examined. Five life-course clusters were identified in the female and six in the male sample. Life courses differed greatly across gender regarding employment aspects (e.g., men generally work full-time vs. women underwent frequent transitions). The family aspects appeared similar – e.g., ‘starting a family’ or ‘marital separation’ clusters – but still differed in the particulars. Life course typologies were related to distinct patterns of HRQoL. For instance, both for men and women the ‘separated’ clusters, as well as the male ‘entering non-employment’ cluster were associated with a steeper decline in HRQoL. However, change in subjective mental health showed few associations. Distinct types of life courses and differential associations with sociodemographic background and HRQoL emerged for women and men. The analyses reveal a burden on individuals who experienced marital separation, and non-employment and thus present important target groups for health prevention, e.g., for physical health problems.
Purpose
Controversies regarding venous compression and trigeminal neuralgia (TN) still exist. The study demonstrates our experience for microvascular decompression (MVD) in TN caused by purely venous compression. The goal was to identify prognostic anatomical or surgical factors that may influence the outcome.
Methods
Between 2004 and 2020, 49 patients were operated with purely venous compression. Average age was 58.4 years. Mean history of TN was 7.8 years. Microsurgical procedures included transposition or separation of the vein, coagulation, and division. Several features have been analyzed with respect to BNI scores.
Results
Evaluation on discharge revealed a complete pain relief in 39 (80%), partial improvement in 7 (14%), and no benefit in 3 (6%) patients. Facial hypesthesia was reported by 14 (28.6%) patients. Mean follow-up (FU) was 42.1 months. BNI pain intensity score on FU revealed 71.4% excellent to very good scores (score 1: 32 (65.3%); 2: 3 (6.1%)). BNI facial numbness score 2 could be detected in 13 patients (26.5%) during FU. There was no statistical relationship between immediate pain improvement or BNI pain intensity score on FU with respect to surgical procedure, size of trigeminal cistern, type of venous compression, venous caliber, trigeminal nerve indentation, or neurovascular adherence. BNI facial numbness score was dependent on type of venous compression (p < 0.05).
Conclusion
We did not find typical anatomical features that could either predict or influence the outcome regarding pain improvement or resolution in any form. Neither classic microvascular decompression (interposition/transposition) nor sacrificing the offending vein made any difference in outcome.
How can powerful states best extract domestic concessions from their junior allies? What are the conditions under which the powerful state is more likely to succeed in inducing such domestic policy change? This article explores the link between US security commitments and Washington’s ability to attain favourable policy outcomes within the allied domestic arena. It provides an illustrative case of how the USA, using security guarantees as leverage, can enter allied domestic space and shape its decision-making process. After it was revealed that Latvia had served as a key node through which North Korea attempted to evade the sanctions regime, the USA, by playing its security guarantor card, pressured Riga to carry out substantial policy reforms in relation to its financial system. This approach yielded considerable results. In order to preserve the existing security arrangements with the dominant alliance member, Latvia offered significant policy concessions. This finding demonstrates that US security alliances come with side benefits that are often underrated or neglected in the scholarly literature.
Is it strategically wise for the USA to stretch its protective umbrella over small nations in Eastern Europe? Prominent critics have faulted US allies for acting recklessly and free-riding on US security guarantees. The evidence presented vis-à-vis the Baltic States, however, challenges these assumptions. This study paints a picture of Estonia, Latvia, and Lithuania as loyalty-obsessed small states that diligently seek to meet their patron’s behavioural expectations. By word and deed, they back US strategic goals. As such, they have taken on heavy war burdens in US-led campaigns and sided with Washington in its geopolitical struggle against China. What is more, they bring to the table distinctive capabilities in cyber and intelligence. In sum, this paper suggests that the Baltic States have continuously reimbursed the USA for its defence-cover services.
Urbanization, industrialization, and intensification of agriculture have led to considerable heavy metal pollution across the globe, harming our ecosystems. Concentrations of arsenic (As), cadmium (Cd), copper (Cu), and lead (Pb) have been analysed in 249 eggshells collected between 2006 and 2021 from 83 female Common Cranes (Grus grus) nesting within north-eastern Germany. Information on the presence of trace elements in cranes from Europe and their potential adverse effects on the reproduction are largely missing. Only Cu and Pb were found to be present in eggshell samples. Levels of both metals did not exceed concentrations considered potentially toxic in birds and unhatched eggs did not contain higher metal concentrations compared to eggshell residues from hatched eggs. Statistical analysis revealed that trace element concentrations decreased significantly over the course of the study period. The ban of leaded gasoline in the early twenty-first century and strict limitations of heavy metal-based biocontrol products are likely responsible for this decrease over the years. However, as Cu levels gradually increase with increasing proportions of agricultural areas within the cranes’ home ranges, we suggest that considerable amounts of Cu originating from agricultural practises are still being released into the environment. We found no increase in metal concentrations in eggshells with increasing female age, suggesting that heavy metals do not accumulate in the circulatory systems of the adults over time. This study is the first to assess heavy metal contamination in Common Cranes and indicates the suitability of crane’s eggshells as bioindicator for monitoring environmental pollution.
The polysaccharide β-mannan, which is common in terrestrial plants but unknown in microalgae, was recently detected during diatom blooms. We identified a β-mannan polysaccharide utilization locus (PUL) in the genome of the marine flavobacterium Muricauda sp. MAR_2010_75. Proteomics showed β-mannan induced translation of 22 proteins encoded within the PUL. Biochemical and structural analyses deduced the enzymatic cascade for β-mannan utilization. A conserved GH26 β-mannanase with endo-activity depolymerized the β-mannan. Consistent with the biochemistry, X-ray crystallography showed the typical TIM-barrel fold of related enzymes found in terrestrial β-mannan degraders. Structural and biochemical analyses of a second GH26 allowed the prediction of an exo-activity on shorter manno-gluco oligosaccharides. Further analysis demonstrated exo-α-1,6-galactosidase- and endo-β-1,4-glucanase activity of the PUL-encoded GH27 and GH5_26, respectively, indicating the target substrate is a galactoglucomannan. Epitope deletion assays with mannanases as analytic tools indicate the presence of β-mannan in the diatoms Coscinodiscus wailesii and Chaetoceros affinis. Mannanases from the PUL were active on diatom β-mannan and polysaccharide extracts sampled during a microalgal bloom at the North Sea. Together these results demonstrate that marine microorganisms use a conserved enzymatic cascade to degrade β-mannans of marine and terrestrial origin and that this metabolic pathway plays a role in marine carbon cycling.
Purpose
Obstructive sleep apnea (OSA) may result in severe health onditions, reduces quality of live, and affects high percentages of the adult population. Due to recent changes in the German health care regulations, mandibular advancement devices (MAD) will become available as a treatment option for OSA to a greater extent for general dentists and their patients.
Methods
A guideline development group consisting of nine members representing four German dental and medical organizations was formed, in order to provide critical information and orientation to the main stakeholders (dentists and patients), regarding the use of MAD for the treatment of OSA within dental sleep medicine.
Results
This guideline aims to inform physicians and dentists, particularly those with acquired qualification/specialization in sleep medicine (or in the diagnosis and treatment of sleep-related breathing disorders), as well as experts, payers, and patients. It delivers recommendations on technical requirements for MAD prescription and fabrication, clinical procedures, maintenance, and follow-up procedures.
Conclusion
A MAD should be designed for long-term therapy and must be a custom made, adjustable, bimaxillary retained two-splint system equipped with adjustable protrusive elements. The fabrication in a dental laboratory should be based on dental impressions or scans and three-dimensional registrations of the starting position taken with a bite gauge.
Measuring mental workload at the workplace using (psycho-) physiological measurement techniques seems desirable but is difficult to implement. Conventional analysis techniques are designed to cover longer measurement durations, neglecting the demands of modern work places: high worker flexibility and constantly fluctuating mental workload. As an alternative analysis approach, measurement (resp. analysis) duration can be shortened and event-based pattern analysis of various physiological parameters can be performed. The effects of such approaches are demonstrated by experimental examples. Furthermore, an event-timestamp independent framework is presented. Focusing on occasionally occurring peaks and longer lasting plateaus in mental workload trajectories, an automatized analysis of workload during work processes becomes possible.
Practical relevance: With steadily increasing cognitive demands at work the risk of mental fatigue increases too. Mental workload is not directly observable at the workplace and the objective measurement and interpretation is complicated. Improving the overall assessment and analysis strategies for (physiological) mental workload indicators can benefit the quality of risk assessments of workplaces and processes as well as enable the possibility of demand-orientated control of (informational) assistance systems to prevent mental overload and resulting health constraints.
Purpose
Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting are well-established treatments of obstructive hydrocephalus (HCP) in adult and pediatric patients. However, there is a lack of data with regard to the quality of life (QoL) of these patients during long-term follow-up
Methods
Inclusion criteria were pediatric patients with endoscopic treatment of hydrocephalus at the University Medicine Greifswald between 1993 and 2016. Patients older than 14 years at present were assessed with the Short Form-12 (SF-12) questionnaire. Patients younger than 14 years of age were assessed with the KINDL-R questionnaire that was completed by their parents. Patients’ values were compared with the scores of a corresponding age-matched group of the healthy population and with patients who received later shunt treatment. Information about comorbidities, current symptoms, and educational level were gained by an additional part. Comparative analysis between patients with ETV success and failure (defined as shunt implantation after ETV) was performed.
Results
A total of 107 patients (53 m, 54f) were included. Fifty-seven/107 patients (53.3%) were considered as ETV success. Mean age at ETV was 6.9 ± 5.9 years. Fifty-four statements of 89 patients that are still alive were gained (response rate 63%). Of these, 49 questionnaires were complete and evaluable (23 m, 26f; mean age 19.8 ± 10.0 years with an average follow-up period of 13.7 ± 7.2 years). Twenty-six/49 patients (53.1%) are considered ETV success. No statistically significant differences could be obtained between patients with ETV success and ETV failure. Patients older 14 years show QoL within normal range, patients younger than 14 years show significantly lower result regarding their environment of peers and social contacts. Patients younger than 6 months at the time of ETV and patients with posthemorrhagic HCP show significantly lower physical QoL. Gait disturbance, fatigue, and seizures are associated with a lower QoL, and educational level is lower than in the normal population.
Conclusions
Patients who underwent ETV in childhood do not have a lower health-related QoL in general. Subsequent insertions of ventriculoperitoneal (vp) shunts do not lower QoL. Certain subgroups of the patients show lower results compared to the healthy population.
Purpose
Outcomes of multiple myeloma (MM) patients who are refractory to daratumumab are dismal and no standard of treatment exists for this patients’ population. Here, we investigate the role of pomalidomide combinations in daratumumab-refractory MM patients.
Methods
We performed a retrospective analysis of myeloma patients treated at four referral centers (three in Germany and one in Italy). Review chart identified 30 patients with relapsed and refractory myeloma, who progressed during treatment with daratumumab and were treated with pomalidomide-based combinations in the subsequent lines of therapy.
Results
Responses improved from 37% with daratumumab to 53% with pomalidomide. Of seven patients with extramedullary MM (EMM), four achieved a clinical stabilization with pomalidomide, including one patient with a long-lasting complete response. Median progression-free survival and overall survival were 6 and 12 months, respectively. Pomalidomide combinations were well tolerated, no patient discontinued treatment due to adverse events.
Conclusion
These data show that pomalidomide-based combinations can be an effective and safe salvage regimen for daratumumab-refractory patients, including those with EMM.
Marine algae produce complex polysaccharides, which can be degraded by marine heterotrophic bacteria utilizing carbohydrate-active enzymes. The red algal polysaccharide porphyran contains the methoxy sugar 6-O-methyl-D-galactose (G6Me). In the degradation of porphyran, oxidative demethylation of this monosaccharide towards D-galactose and formaldehyde occurs, which is catalyzed by a cytochrome P450 monooxygenase and its redox partners. In direct proximity to the genes encoding for the key enzymes of this oxidative demethylation, genes encoding for zinc-dependent alcohol dehydrogenases (ADHs) were identified, which seem to be conserved in porphyran utilizing marine Flavobacteriia. Considering the fact that dehydrogenases could play an auxiliary role in carbohydrate degradation, we aimed to elucidate the physiological role of these marine ADHs. Although our results reveal that the ADHs are not involved in formaldehyde detoxification, a knockout of the ADH gene causes a dramatic growth defect of Zobellia galactanivorans with G6Me as a substrate. This indicates that the ADH is required for G6Me utilization. Complete biochemical characterizations of the ADHs from Formosa agariphila KMM 3901T (FoADH) and Z. galactanivorans DsijT (ZoADH) were performed, and the substrate screening revealed that these enzymes preferentially convert aromatic aldehydes. Additionally, we elucidated the crystal structures of FoADH and ZoADH in complex with NAD+ and showed that the strict substrate specificity of these new auxiliary enzymes is based on a narrow active site.
Beta-2-glycoprotein I (β2GPI) is a blood protein and the major antigen in the autoimmune disorder
antiphospholipid syndrome (APS). β2GPI exists mainly in closed or open conformations and
comprises of 11 disulfides distributed across five domains. The terminal Cys288/Cys326 disulfide
bond at domain V has been associated with different cysteine redox states. The role of this disulfide
bond in conformational dynamics of this protein has not been investigated so far. Here, we report
on the enzymatic driven reduction by thioredoxin-1 (recycled by Tris(2-carboxyethyl)phosphine;
TCEP) of β2GPI. Specific reduction was demonstrated by Western blot and mass spectrometry
analyses confirming majority targeting to the fifth domain of β2GPI. Atomic force microscopy images
suggested that reduced β2GPI shows a slightly higher proportion of open conformation and is more
flexible compared to the untreated protein as confirmed by modelling studies. We have determined a
strong increase in the binding of pathogenic APS autoantibodies to reduced β2GPI as demonstrated
by ELISA. Our study is relevant for understanding the effect of β2GPI reduction on the protein
structure and its implications for antibody binding in APS patients.
Facing climate change, the development of innovative agricultural technologies securing food production becomes increasingly important. Plasma-treated water (PTW) might be a promising tool to enhance drought stress tolerance in plants. Knowledge about the effects of PTW on the physiology of plants, especially on their antioxidative system on a long-term scale, is still scarce. In this work, PTW was applied to barley leaves (Hordeum vulgare cv. Kosmos) and various constituents of the plants’ antioxidative system were analyzed 30 days after treatment. An additional drought stress was performed after foliar PTW application followed by a recovery period to elucidate whether PTW treatment improved stress tolerance. Upon PTW treatment, the Total Antioxidant Capacity (TAC) in leaves and roots was lower in comparison to deionized water treated plants. In contrast, PTW treatment caused a higher content of chlorophyll, quantum yield and total ascorbate content in leaves compared to deionized water treated plants. After additional drought application and subsequent recovery period, an enhancement of values for TAC, contents of malondialdehyde, glutathione as well as activity of ascorbate peroxidase indicated a possible upregulation of antioxidative properties in roots. Hydrogen peroxide and nitric oxide might mediate abiotic stress tolerance and are considered as key components of PTW.
The multi-level perspective has been criticized for being functionalistic and paying little attention to actor-based perspectives. Nevertheless, for the identification and assessment of potential change agents in a sustainability transition, a clear conceptual and methodological approach is necessary. This paper, thus, develops a multi-dimensional typology of niche, regime, and hybrid actors, which is conceptually grounded in transition studies and empirically illustrated by a cluster analysis based on a survey of pig and poultry farmers in Germany, France, and the Netherlands. Animal husbandry is chosen as a case study because a significant share of the environmental impact within the agri-food system is attributed to this sector and there is evidence for resistance to change by mainstream actors. Conceptually, the paper provides a framework of constitutive elements for different kinds of actors and contributes to an extension of the niche–regime dichotomy by adding the group of hybrid actors. The empirical results show that cluster analysis is a suitable approach to identify conceptually meaningful differences among interviewed farmers. Among pig and poultry farmers, the regime actors are by far the largest group. The smaller group of hybrid actors, however, has large potential to act as boundary spanners. A particularly interesting finding is that several larger farms are among the group of niche actors which hints at the possibility that larger farms are not necessarily resistant to change.
Purpose
Oxidative stress has been linked to initiation and progression of cancer and recent studies have indicated a potential translational role regarding modulation of ROS in various cancers, including acute myeloid leukemia (AML). Detailed understanding of the complex machinery regulating ROS including its producer elements in cancer is required to define potential translational therapeutic use. Based on previous studies in acute myeloid leukemia (AML) models, we considered NADPH oxidase (NOX) family members, specifically NOX4 as a potential target in AML.
Methods
Pharmacologic inhibition and genetic inactivation of NOX4 in murine and human models of AML were used to understand its functional role. For genetic inactivation, CRISPR-Cas9 technology was used in human AML cell lines in vitro and genetically engineered knockout mice for Nox4 were used for deletion of Nox4 in hematopoietic cells via Mx1-Cre recombinase activation.
Results
Pharmacologic NOX inhibitors and CRISPR-Cas9-mediated inactivation of NOX4 and p22-phox (an essential NOX component) decreased proliferative capacity and cell competition in FLT3-ITD-positive human AML cells. In contrast, conditional deletion of Nox4 enhanced the myeloproliferative phenotype of an FLT3-ITD induced knock-in mouse model. Finally, Nox4 inactivation in normal hematopoietic stem and progenitor cells (HSPCs) caused a minor reduction in HSC numbers and reconstitution capacity.
Conclusion
The role of NOX4 in myeloid malignancies appears highly context-dependent and its inactivation results in either enhancing or inhibitory effects. Therefore, targeting NOX4 in FLT3-ITD positive myeloid malignancies requires additional pre-clinical assessment.
Background
One of the main treatment goals in cochlear implant (CI) patients is to improve speech perception. One of the target parameters is speech intelligibility in quiet. However, treatment results show a high variability, which has not been sufficiently explained so far. The aim of this noninterventional retrospective study was to elucidate this variability using a selected population of patients in whom etiology was not expected to have a negative impact on postoperative speech intelligibility.
Materials and methods
Audiometric findings of the CI follow-up of 28 adult patients after 6 months of CI experience were evaluated. These were related to the preoperative audiometric examination and evaluated with respect to a recently published predictive model for the postoperative monosyllabic score.
Results
Inclusion of postoperative categorical loudness scaling and hearing loss for Freiburg numbers in the model explained 55% of the variability in fitting outcomes with respect to monosyllabic word recognition.
Conclusion
The results of this study suggest that much of the cause of variability in fitting outcomes can be captured by systematic postoperative audiometric checks. Immediate conclusions for CI system fitting adjustments may be drawn from these results. However, the extent to which these are accepted by individual patients and thus lead to an improvement in outcome must be subject of further studies, preferably prospective.
SLC35F1 is a member of the sugar-like carrier (SLC) superfamily that is expressed in the mammalian brain. Malfunction of SLC35F1 in humans is associated with neurodevelopmental disorders. To get insight into the possible roles of Slc35f1 in the brain, we generated Slc35f1-deficient mice. The Slc35f1-deficient mice are viable and survive into adulthood, which allowed examining adult Slc35f1-deficient mice on the anatomical as well as behavioral level. In humans, mutation in the SLC35F1 gene can induce a Rett syndrome-like phenotype accompanied by intellectual disability (Fede et al. Am J Med Genet A 185:2238–2240, 2021). The Slc35f1-deficient mice, however, display only a very mild phenotype and no obvious deficits in learning and memory as, e.g., monitored with the novel object recognition test or the Morris water maze test. Moreover, neuroanatomical parameters of neuronal plasticity (as dendritic spines and adult hippocampal neurogenesis) are also unaltered. Thus, Slc35f1-deficient mice display no major alterations that resemble a neurodevelopmental phenotype.
Binding of general transcription factors TFIID and TFIIA to basal promoters is rate-limiting for transcriptional initiation of eukaryotic protein-coding genes. Consequently, activator proteins interacting with subunits of TFIID and/or TFIIA can drastically increase the rate of initiation events. Yeast transcriptional activator Ino2 interacts with several Taf subunits of TFIID, among them the multifunctional Taf1 protein. In contrast to mammalian Taf1, yeast Taf1 lacks bromodomains which are instead encoded by separate proteins Bdf1 and Bdf2. In this work, we show that Bdf1 not only binds to acetylated histone H4 but can also be recruited by Ino2 and unrelated activators such as Gal4, Rap1, Leu3 and Flo8. An activator-binding domain was mapped in the N-terminus of Bdf1. Subunits Toa1 and Toa2 of yeast TFIIA directly contact sequences of basal promoters and TFIID subunit TBP but may also mediate the influence of activators. Indeed, Ino2 efficiently binds to two separate structural domains of Toa1, specifically with its N-terminal four-helix bundle structure required for dimerization with Toa2 and its C-terminal β-barrel domain contacting TBP and sequences of the TATA element. These findings complete the functional analysis of yeast general transcription factors Bdf1 and Toa1 and identify them as targets of activator proteins.
Phylogenetic (i.e., leaf-labeled) trees play a fundamental role in evolutionary research. A typical problem is to reconstruct such trees from data like DNA alignments (whose columns are often referred to as characters), and a simple optimization criterion for such reconstructions is maximum parsimony. It is generally assumed that this criterion works well for data in which state changes are rare. In the present manuscript, we prove that each binary phylogenetic tree T with n ≥ 20k leaves is uniquely defined by the set Ak (T), which consists of all characters with parsimony score k on T. This can be considered as a promising first step toward showing that maximum parsimony as a tree reconstruction criterion is justified when the number of changes in the data is relatively small.
Cationic and anionic clusters of the group-14 elements carbon, silicon, germanium, tin, and lead are produced by high-vacuum laser ablation and studied with a multi-reflection time-of-flight mass spectrometer. In-trap photodissociation is performed for cluster species in the size range n=2–10. The clusters’ production rates as well as their dissociation pathways are used to probe the nonmetal–metal transition throughout the group. Carbon clusters show neutral-trimer break-off, while those of the other elements evaporate neutral monomers and, in some cases, form specific charged fragment sizes.
Indications for surgery of pineal cysts without ventriculomegaly are still under debate. In view of the limited data for pineal cyst resection in the absence of hydrocephalus, and the potential risk of this approach, we have analyzed our patient cohort focusing on strategies to avoid complications according to our experience in a series of 73 pineal cyst patients. From 2003 to 2015, we reviewed our database retrospectively for all patients operated on a pineal cyst. Furthermore, we prospectively collected patients from 2016 to 2020. In summary, 73 patients with a pineal cyst were treated surgically between 2003 and 2020. All patients were operated on via a microscopic supracerebellar-infratentorial (SCIT) approach. The mean follow-up period was 26.6 months (range: 6–139 months). Seventy-three patients underwent surgery for a pineal cyst. An absence of enlarged ventricles was documented in 62 patients (51 female, 11 male, mean age 28.1 (range 4–59) years). Main presenting symptoms included headache, visual disturbances, dizziness/vertigo, nausea/emesis, and sleep disturbances. Complete cyst resection was achieved in 59/62 patients. Fifty-five of 62 (89%) patients improved after surgery with good or even excellent results according to the Chicago Chiari Outcome Scale, with complete or partial resolution of the leading symptoms. Pineal cysts resection might be an indication in certain patients for surgery even in the absence of ventriculomegaly. The high percentage of postoperative resolution of quality-of-life impairing symptoms in our series seems to justify surgery. Preoperatively, other causes of the leading symptoms have to be excluded.
Epidemiological data reveal that there is a need for prevention measures specifically targeted at children with low SES. In the German federal state Mecklenburg-Western Pomerania preschools in socially deprived regions can apply for additional funds to support children with developmental risks. Mandatory criteria for obtaining these funds involve an annual assessment of all children using the “Dortmunder Developmental Screening for Preschools (DESK 3–6 R).” This instrument can detect and monitor developmental risks in the domains fine motor skills, gross motor skills, language, cognition, and social development. In this study, we examine the domain “Attention and concentration,” which is included for the 5 to 6-year-old age group, using data from two consecutive survey waves (sw). Research questions: (1) Does the prevalence rate ratio (PRR) improve over time? (2) Is the rate of improvements (developmental risk at sw1, no developmental risk at sw2) higher than the rate of deteriorations (no developmental risk at sw1, developmental risk at sw2)? Prospective cohort analysis (n = 940). The prevalence rate of a developmental risk in this DESK domain decreases over time (PRR = 0.78; p = 0.019). The ratio of the rate of improvements is 8.47 times higher than the rate of deteriorations. The results provide evidence of the effectiveness of targeted intervention measures in preschools focusing on skills that improve attention and concentration. This is significant considering the small-time interval and the categorization method of DESK scores. Nevertheless, over the same time period, the DESK results of some children deteriorated. Therefore, preschools also have to be aware that it is natural for some children to show modest declines in their skills over time. German Clinical Trials Register, ID: DRKS00015134, Registered on 29 October 2018, retrospectively registered.
Purpose
Mixing with liquids or soft foods is a common procedure to improve acceptability of oral medicines in children but may affect drug stability and the in vivo performance of the administered drug product. The aim of the present study was to obtain an overview of the variability of critical attributes of commonly used vehicles and to identify which vehicle characteristics need to be considered when developing in vitro methods for evaluating product quality.
Methods
One product of each vehicle listed in the FDA draft guidance “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration” was analyzed with regard to composition, calorific content and physicochemical properties.
Results
The studied vehicles show wide variability, both in composition and physicochemical properties. No correlation was observed between vehicle composition and physicochemical properties. Comparison of results of the present study with previously published data also provided variability in physicochemical properties within individual vehicle types.
Conclusions
To identify acceptable (qualified) vehicles for global drug product labeling, it is important that the vehicles selected for in vitro compatibility screening reflect the variability in composition and essential physicochemical properties of the vehicles recommended on the product label, rather than relying on results obtained with a single vehicle of each type. Future activities will focus on the development of standardized dosing vehicles that can represent key vehicle characteristics in all their variability to ensure reliable risk assessment.
Perception of climate change-related forest dieback in mountain forests among the local population
(2023)
Mountain forests provide multiple benefits but are threatened by climate change-induced forest dieback. Although many studies summarize perceptions of forest ecosystem services, relatively few deal with mountain forests. The local population’s perception of forest dieback in mountain forests in relation to climate change has rarely been investigated so far. Their perspective is relevant as local people are often deeply attached to “their” forests, they actively use forest ecosystems and—as voters and taxpayers—they need to support the state’s adaptation and funding measures. Therefore, this study investigates the climate change and forest dieback perception of local inhabitants in two mountain areas of Southern Germany (the German Alps and the Bavarian Forest) with a quantitative survey based on representative online samples (n = 709). Relying conceptually on van der Linden’s (J Environ Psychol 41:112–124, 2015. https://doi.org/10.1016/j.jenvp.2014.11.012) climate change risk perception model, the results show that experiential processing, cognitive and socio-cultural factors are related to locals’ forest dieback and climate change perception, while socio-demographics show no or few connections. Nearly two-thirds (64.7%) of the respondents perceive moderate to strong forest dieback, while more than half (55.0%) of the respondents already observe consequences of climate change. The perceptions of climate change and forest dieback are positively correlated with medium to high strength. This shows that forest dieback could be interpreted as an indicator of climate change, which is difficult to observe due to its long-term nature. We identify three groups of respondents regarding preferred forest adaptation strategies to climate change. In general, respondents support nature-based forest adaptation strategies over intense measures.
Introduction
Tibial tubercle osteotomy (TTO) is a common procedure used to treat patients with patellofemoral instability (PFI) and osteoarthritis (PFOA). Medial patellar maltracking due to previous excessive medialization of the tibial tubercle has rarely been reported. Therefore, the goal of this study was to assess patient-reported outcome measures (PROMs) after revision osteotomy with lateralization of the tibial tubercle (RL-TTO) to correct medial patellofemoral maltracking.
Materials and methods
Between 2017 and 2021, a series of 11 patients (male/female 1/10; age 35.8 ± 10.5 years) were treated by RL-TTO, of whom 8 patients could be retrospectively evaluated after a mean of 32.4 ± 15.1 months (range 18–61 months) postoperatively. The Kujala anterior knee pain scale, the patellofemoral subscale of the Knee Osteoarthritis and Outcome Score (KOOS-PF), and a numeric analog scale (NAS; 0–10) regarding anterior knee pain (AKP) at rest and during activity were assessed from pre- to postoperatively.
Results
The preoperative mean tibial tubercle-trochlear groove (TT-TG) and tibial tubercle-posterior cruciate ligament (TT-PCL) distances were − 6.5 ± 6.5 mm and 0.7 ± 4.6 mm, respectively. The intraoperatively determined amount of tibial tubercle lateralization averaged 10.7 ± 3.6 mm. The Kujala score and KOOS-PF improved significantly from 33.6 ± 10.1 (23–51) points to 94.4 ± 6.2 points (82–100) (p < 0.001) and from 20.6 ± 13.2 points (0–43.3) to 87.3 ± 9.9 points (72.8–100) (p < 0.001) from pre- to postoperatively, respectively. Pain at rest decreased from 5.8 ± 1.9 to 0.8 ± 0.9 (p < 0.001), and pain during activity decreased from 8.6 ± 1.3 to 1.6 ± 1.5 (p < 0.001).
Conclusion
RL-TTO significantly improved subjective knee function and AKP in patients suffering from medial patellar maltracking due to previous excessive tibial tubercle medialization osteotomy at short-term follow-up.
Late Pleistocene glacitectonism at the southern Scandinavian Ice Sheet margin caused folding and thrusting of Upper Cretaceous chalk layers and Pleistocene glacial deposits in parts of the southwestern Baltic Sea area in Europe. Beside Møns Klint (SE Denmark), the Jasmund Glacitectonic Complex (JGC) on Rügen Island (NE Germany) is a similar striking example of glacitectonic deformation creating large composite ridges. In spite of a long research history and new results from modern datasets, the structural development of the JGC is still poorly understood, especially the detailed evolution of the southern JGC and its relationship to the northern JGC remain enigmatic. In this contribution, we demonstrate how the understanding of the JGC benefits from the application of established structural geological methods comprehending the formation of fold-and-thrust belts. The methods include cross-section balancing of the eastern coast (southern JGC) and quantification of the amount of folding and faulting. The proposed geometric model shows the current fold-and-thrust stack of glacially deformed sedimentary strata ca. 5720 m in length evolved by shortening from the original length (11,230 m) by 5510 m (49.1%). We present a spatial and temporal development of fault-related folding with a transition from detachment folds through fault-propagation folds to fault-bend folds. Together with morphological information from a digital elevation model, the thrust faults mapped in the cliff section are mainly inclined towards the S to SW and imply that a local glacier push occurred from the south. These results highlight the complexity and individual architecture of the JGC when compared to other Pleistocene and modern glacitectonic complexes. Resolving its structural development provides new insight into the deformation history and shortening of this spectacular glacitectonic complex lying in the southwestern Baltic Sea region.
Despite their very close structural similarity, CxxC/S-type (class I) glutaredoxins (Grxs) actas oxidoreductases, while CGFS-type (class II) Grxs act as FeS cluster transferases. Here weshow that the key determinant of Grx function is a distinct loop structure adjacent to theactive site. Engineering of a CxxC/S-type Grx with a CGFS-type loop switched its functionfrom oxidoreductase to FeS transferase. Engineering of a CGFS-type Grx with a CxxC/S-typeloop abolished FeS transferase activity and activated the oxidative half reaction of the oxi-doreductase. The reductive half-reaction, requiring the interaction with a second GSHmolecule, was enabled by switching additional residues in the active site. We explain howsubtle structural differences, mostly depending on the structure of one particular loop, act inconcert to determine Grx function.
Flies are implicated in carrying and mechanically transmitting many primate pathogens. We investigated how fly associations vary across six monkey species (Cercopithecus ascanius, Cercopithecus mitis, Colobus guereza, Lophocebus albigena, Papio anubis, and Piliocolobus tephrosceles) and whether monkey group size impacts fly densities. Fly densities were generally higher inside groups than outside them, and considering data from these primate species together revealed that larger groups harbored more flies. Within species, this pattern was strongest for colobine monkeys, and we speculate this might be due to their smaller home ranges, suggesting that movement patterns may influence fly–primate associations. Fly associations increase with group sizes and may thus represent a cost to sociality.
Purpose
A setting-sensitive instrument for assessing Quality of Life (QoL) in Telemedicine (TM) was unavailable. To close this gap, a content-valid “add-on” measure was developed. In parallel, a brief index was derived featuring six items that summarise the main content of the multidimensional assessment. After pre- and pilot-testing, the psychometric performance of the final measures was investigated in an independent validation study.
Methods
The questionnaires were applied along with other standardised instruments of similar concepts as well as associated, yet disparate concepts for validation purposes. The sample consisted of patients with depression or heart failure, with or without TM (n = 200). Data analyses were aimed at calculating descriptive statistics and testing the psychometric performance on item, scale, and instrument level, including different types of validity and reliability.
Results
The proposed factor structure of the multidimensional Tele-QoL measure has been confirmed. Reliability coefficients for internal consistency, split-half, and test-retest reliability of the subscales and index reached sufficient values. The Tele-QoL subscales and the index demonstrated Rasch scalability. Validity of both instruments can be assumed. Evidence for discriminant construct validity was provided. Known-groups validity was indicated by respective score differences for various classes of disease severity.
Conclusion
Both measures show convincing psychometric properties. The final multidimensional Tele-QoL assessment consists of six outcome scales and two impact scales assessing (un-)intended effects of TM on QoL. In addition, the Tele-QoL index provides a short alternative for outcome assessment. The Tele-QoL measures can be used as complementary modules to existing QoL instruments capturing healthcare-related aspects of QoL from the patients’ perspective.
Lacewings (Neuroptera) have predatory larvae with highly specialised mouthparts. Larvae of many groups within Neuroptera are well represented as fossils preserved in ambers; however, larvae of some groups are less often reported in the literature. Here we report such a rare case, a larva of the group Hemerobiidae, an aphidlion, preserved in a piece of Eocene Baltic amber (about 40 million years old). It is preserved together with three possible prey items, wingless aphids, most likely representatives of Germaraphis (or at least closely related to this group). The aphidlion can be identified based on the morphology of the antennae, simple curved and toothless stylets, well developed labial palps, and the absence of other mouth-part structures such as a protruding labrum or maxillary palps. A long, club-shaped distal element of the labial palps identifies the specimen as a larva of Hemerobiidae. The aphids can be identified based on their very long, beak-like mouth parts. This find is, to our knowledge, the first example of a lacewing larva preserved together with its potential prey. We briefly discuss other cases in which fossils preserved in amber allow us to reconstruct aspects of behaviour and interactions of fossil lacewing larvae.
Lack of a shared vision has been identified as a major obstacle in transdisciplinary research involving both scientists and other stakeholders. Without a shared vision, the implementation of scientific findings is difficult. The diverse partners of collaborative research, however, imply a plurality in the valuation of nature and a need for deliberative mechanisms. If visioning processes are to do justice to local contexts, research must apply deliberative mechanisms to cover the plurality in the valuation of nature. This paper proposes a visioning approach for local communities, based on prior transdisciplinary research. This participatory workshop method invites stakeholders to approach nature conservation and livelihoods via a deliberation of desirable futures, barriers for achieving them and associated responsibilities for taking action. The paper explores this method via a case study of visioning workshops on sacred swamps in the Western Ghats (India), and their role for both freshwater swamp protection and livelihoods. The visioning exercise offered discussion opportunities facilitating conscientization, conciliation and collaboration in local bottom-up nature conservation. For conserving the tropical freshwater swamps, the results show the need for a more participatory forest governance, providing space for shared value creation. They also point to the need for further research on inter-faith nature conservation possibilities, along with innovations on value addition and value chain development for livelihood promotion and protection.
In wet peatlands, plant growth conditions are largely determined by local soil conditions, leading to locally adapted vegetation. Despite that Carex species are often the prevailing vascular plant species in fen peatlands of the temperate zone, information about how these species adapt to local environmental conditions is scarce. This holds true especially for below-ground plant traits and for adaptations to fen-typical nutrient level variations. To address this research gap, we investigated how different geographic origins (Germany, Poland, The Netherlands) of C. acutiformis and C. rostrata relate to their response to varying nutrient availability. We performed a common garden experiment with a controlled gradient of nutrient levels, and analyzed above- and below-ground biomass production of both Carex species from the different geographic origins. We related these traits to environmental conditions of the origins as characterized by vegetation composition-derived indicator values for ecological habitat conditions. While we detected high above-ground phenotypic plasticity of Carex from different origins, our data point to below-ground genotypic differences, potentially indicating local adaptation: Rhizome traits of C. rostrata differed significantly between origins with different nutrient indicator values. These results point towards differences in C. rostrata clonal spread behavior depending on local peatland conditions. Therefore, local adaptations of plant species and below-ground biomass traits should be taken into account when studying peatland vegetation ecology, as key functional traits can differ between genotypes within a single species depending on local conditions.
A hollow cathode discharge with a Ti cathode and a positively biased ring anode was operated in Ar + N2 or Ar + O2 gas mixtures. The energy distribution of plasma ions is investigated with the help of energy-resolved mass spectrometry. Singly and doubly charged Ar+ and Ar2+ ions and molecular N+2 or O+2 ions are the most abundant ionic species. The kinetic energy of all plasma ions is enhanced by a positive anode voltage.
The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.
Flies form high-density associations with human settlements and groups of nonhuman primates and are implicated in transmitting pathogens. We investigate the movement of nonhuman primate-associated flies across landscapes surrounding Kibale National Park, Uganda, using a mark–recapture experiment. Flies were marked in nine nonhuman primate groups at the forest edge (x̄ = 929 flies per group), and we then attempted to recapture them in more anthropized areas (50 m, 200 m and 500 m from where marked; 2–21 days after marking). Flies marked in nonhuman primate groups were recaptured in human areas (19/28,615 recaptured). Metabarcoding of the flies in nonhuman primate groups revealed the DNA of multiple eukaryotic primate parasites. Taken together, these results demonstrate the potential of flies to serve as vectors between nonhuman primates, livestock and humans at this biodiverse interface.
The extent to which the left–right dimension still structures party systems in highly developed, industrialized democracies is a contested field in comparative politics. Most studies in this area take the position that a stable and universal left–right dimension is either still the most important game in town or has become obsolete and replaced by other policy dimensions. Although country-specific studies focusing on voters’ left–right self-placement discover different meanings of left and right that vary between countries and change over time, few macro-comparative studies focusing on parties or governments take this aspect into account. Using a left–right concept for party politics from the PIP project on Parties, Institutions and Preferences that distinguishes an ideological core derived from political theory, as well as country- and time-specific issues uncovered through empirical analysis, the article demonstrates fundamental differences in the relevance and meaning of left and right by analyzing 34 party systems from 1945 to 2020. The article shows that the thesis of the decline of the left and right is premature. An important aspect for the continued high relevance of the left–right dimension is the fact that left and right changes their meaning by including controversial issues such as European integration, migration and environmental degradation.
Objective
To conduct a systematic review of the published scientific evidence to evaluate the efficacy of nonsurgical periodontal therapy (NSPT) in treating periodontitis in patients with concurrent systemic conditions (diabetes, CVD, erectile dysfunction, chronic kidney disease, rheumatoid arthritis, polycystic ovarian syndrome, obesity, pregnancy). We hypothesised that NSPT results in better periodontal outcomes when compared to untreated controls after follow-up.
Materials and methods
A systematic search (PUBMED/EMBASE) was conducted from 1995 to 2023 to identify randomised controlled trials (RCTs) with a minimum follow-up of 3 months. The primary outcome was the difference in mean probing depth (PD), and the secondary outcomes were mean clinical attachment loss (CAL), percentage of sites with PD ≤ 3 mm (%PD ≤ 3 mm) and percentage of sites with bleeding on probing (%BOP) between the treated and untreated control group in patients with comorbidities.
Results
The electronic search resulted in 2,403 hits. After removing duplicates, 1,565 titles and abstracts were screened according to the eligibility criteria, resulting in 126 articles for full-text screening. Following this, 44 studies were analysed. Restricting to studies with low bias or some concerns, NSPT group demonstrated a 0.55 mm lower mean PD (95%CI: −0.69; −0.41) after 3 months compared to the control group.
Conclusion
Compared to the untreated controls, NSPT notably reduced mean PD, mean CAL, and %BOP while increasing %PD ≤ 3 mm in patients with concurrent systemic conditions. These findings suggest that NSPT is also an effective procedure in managing periodontitis in patients with concurrent systemic conditions.
Trial registration
This systematic review was registered under the protocol registration number CRD42021241517/PROSPERO.
The renal renin-angiotensin system (RAS) is involved in the development of chronic kidney disease. Here, we investigated whether mice with reduced renal angiotensin I-converting enzyme (ACE−/−) are protected against aristolochic acid nephropathy (AAN). To further elucidate potential molecular mechanisms, we assessed the renal abundances of several major RAS components. AAN was induced using aristolochic acid I (AAI). Glomerular filtration rate (GFR) was determined using inulin clearance and renal protein abundances of renin, angiotensinogen, angiotensin I-converting enzyme (ACE) 2, and Mas receptor (Mas) were determined in ACE−/− and C57BL/6J control mice by Western blot analyses. Renal ACE activity was determined using a colorimetric assay and renal angiotensin (Ang) (1–7) concentration was determined by ELISA. GFR was similar in vehicle-treated mice of both strains. AAI decreased GFR in controls but not in ACE−/− mice. Furthermore, AAI decreased renal ACE activity in controls but not in ACE−/− mice. Vehicle-treated ACE−/− mice had significantly higher renal ACE2 and Mas protein abundances than controls. AAI decreased renal ACE2 protein abundance in both strains. Furthermore, AAI increased renal Mas protein abundance, although the latter effect did not reach statistical significance in the ACE−/− mice. Renal Ang(1–7) concentration was similar in vehicle-treated mice of both strains. AAI increased renal Ang(1–7) concentration in the ACE−/− mice but not in the controls. Mice with reduced renal ACE are protected against AAN. Our data suggest that in the face of renal ACE deficiency, AAI may activate the ACE2/Ang(1–7)/Mas axis, which in turn may deploy its reno-protective effects.
In general, concepts such as chemical equilibria and classical analytical chemistry, as well as instrumental methods such as potentiometry and flow injection analysis (FIA), are taught separately in the curricula of chemistry-related degree programs. However, FIA provides an opportunity to connect all of these important topics. This article shows how simple experiments can be used to link the fundamentals of FIA and potentiometry to the fundamentals of chemical equilibria and teach them in a sustainable way. The experiments were designed for undergraduate environmental science students with basic knowledge of chemical equilibria and classical analytical chemistry and minimal knowledge of electrochemistry. However, they can also be integrated into various courses on instrumental analysis in chemistry-related degree programs.
Objectives
Biofilm removal is the decisive factor for the control of peri-implantitis. Cold atmospheric pressure plasma (CAP) can become an effective aid due to its ability to destroy and to inactivate bacterial biofilm residues. This study evaluated the cleaning efficiency of CAP, and air-polishing with glycine (APG) or erythritol (APE) containing powders alone or in combination with CAP (APG + CAP, APE + CAP) on sandblasted/acid etched, and anodised titanium implant surface.
Materials and methods
On respective titanium discs, a 7-day ex vivo human biofilm was grown. Afterwards, the samples were treated with CAP, APG, APE, APG + CAP, and APE + CAP. Sterile and untreated biofilm discs were used for verification. Directly after treatment and after 5 days of incubation in medium at 37 °C, samples were prepared for examination by fluorescence microscopy. The relative biofilm fluorescence was measured for quantitative analyses.
Results
Air-polishing with or without CAP removed biofilms effectively. The combination of air-polishing with CAP showed the best cleaning results compared to single treatments, even on day 5. Immediately after treatment, APE + CAP showed insignificant higher cleansing efficiency than APG + CAP.
Conclusions
CAP supports mechanical cleansing and disinfection to remove and inactivate microbial biofilm on implant surfaces significantly. Here, the type of the powder was not important. The highest cleansing results were obtained on sandblasted/etched surfaces.
Clinical relevance.
Microbial residuals impede wound healing and re-osseointegration after peri-implantitis treatment. Air-polishing treatment removes biofilms very effectively, but not completely. In combination with CAP, microbial free surfaces can be achieved. The tested treatment regime offers an advantage during treatment of peri-implantitis.
Animal species differ considerably in longevity. Among mammals, short-lived species such as shrews have a maximum lifespan of about a year, whereas long-lived species such as whales can live for more than two centuries. Because of their slow pace of life, long-lived species are typically of high conservation concern and of special scientific interest. This applies not only to large mammals such as whales, but also to small-sized bats and mole-rats. To understand the typically complex social behavior of long-lived mammals and protect their threatened populations, field studies that cover substantial parts of a species’ maximum lifespan are required. However, long-term field studies on mammals are an exception because the collection of individualized data requires considerable resources over long time periods in species where individuals can live for decades. Field studies that span decades do not fit well in the current career and funding regime in science. This is unfortunate, as the existing long-term studies on mammals yielded exciting insights into animal behavior and contributed data important for protecting their populations. Here, I present results of long-term field studies on the behavior, demography, and life history of bats, with a particular focus on my long-term studies on wild Bechstein’s bats. I show that long-term studies on individually marked populations are invaluable to understand the social system of bats, investigate the causes and consequences of their extraordinary longevity, and assess their responses to changing environments with the aim to efficiently protect these unique mammals in the face of anthropogenic global change.
The aim of this study was to investigate the impact of resilience, alexithymia and the subjectively perceived severity (fear of death, pain intensity, helplessness) of myocardial infarction (MI) on posttraumatic symptom severity (PTSS) after MI. Patients were assessed with the Posttraumatic Diagnostic Scale (PDS), Resilience Scale (RS-11) and Toronto Alexithymia Scale (TAS-20). Subjectively perceived severity of MI was measured with three items on a 10-point Likert scale. To test our hypothesis, we applied Pearson correlations as well as multiple hierarchical linear regression analyses. A higher resilience score was significantly associated with lower (r = − .39, p < .001) PTSS. Higher scores of alexithymia (r = .38, p < .01) and subjectively perceived helplessness (r = .42, p < .001) were associated with higher PTSS. Multiple hierarchical linear regression analyses revealed that resilience, the TAS-20 subscale difficulty identifying feelings (DIF) and especially subjectively perceived helplessness were independent significant predictors for the PTSS, adjusted R2 = .29, F(5, 102) = 9.57, p < .001. Our results suggest that resilience reduces the PTSS whereas alexithymia and subjectively perceived helplessness increase the risk. Especially the subjectively perceived helplessness explains a high degree of variance of PTSS and should be assessed to hindering further mental health burden.
Circular economies are an important pillar of sustainable production and consumption. This particularly applies to the agri-food industry, which is characterised by large amounts of organic waste and by-product streams posing a serious challenge for many food producers. Therefore, respective firms increasingly adopt circular economy business models (CEBMs) to manage these resource flows effectively. However, there is only little knowledge on the functioning of CEBMs in bio-based industries, especially from a socio-economic perspective. We address this gap by exploring enablers and motivations behind such business models as well as the institutional contexts they are embedded in. In methodological terms, we adopt a case study approach using the example of potato production in Lower Saxony (northwest Germany). The core of the paper is a qualitative in-depth analysis of four potato processors, adopting varying business models to valorise their by-product streams (e.g. peels, scraps, pulp) either ‘in-house’ or in partnerships with external partners. The findings show that the implementation of CEBMs results from a complex interplay of internal and external enablers, with economic considerations as the main impetus for the management of biological reverse cycles. Thereby, we found a shifting economic logic in the assessment of potato by-products from disposable waste to valuable resources for other sectors (e.g. livestock farming, bioenergy, biofuels). While being encouraged by targeted policies, the companies studied feel increasingly affected by emerging sustainability discourses, prompting them to (re)design and (re)frame their CEBMs in view of environmental and societal issues.
Characterization of proteins from the 3N5M family reveals an operationally stable amine transaminase
(2022)
Amine transaminases (ATA) convert ketones into optically active amines and are used to prepare active pharmaceutical ingredients and building blocks. Novel ATA can be identified in protein databases due to the extensive knowledge of sequence-function relationships. However, predicting thermo- and operational stability from the amino acid sequence is a persisting challenge and a vital step towards identifying efficient ATA biocatalysts for industrial applications. In this study, we performed a database mining and characterized selected putative enzymes of the β-alanine:pyruvate transaminase cluster (3N5M) — a subfamily with so far only a few described members, whose tetrameric structure was suggested to positively affect operational stability. Four putative transaminases (TA-1: Bilophilia wadsworthia, TA-5: Halomonas elongata, TA-9: Burkholderia cepacia, and TA-10: Burkholderia multivorans) were obtained in a soluble form as tetramers in E. coli. During comparison of these tetrameric with known dimeric transaminases we found that indeed novel ATA with high operational stabilities can be identified in this protein subfamily, but we also found exceptions to the hypothesized correlation that a tetrameric assembly leads to increased stability. The discovered ATA from Burkholderia multivorans features a broad substrate specificity, including isopropylamine acceptance, is highly active (6 U/mg) in the conversion of 1-phenylethylamine with pyruvate and shows a thermostability of up to 70 °C under both, storage and operating conditions. In addition, 50% (v/v) of isopropanol or DMSO can be employed as co-solvents without a destabilizing effect on the enzyme during an incubation time of 16 h at 30 °C.
Osteoporosis, a complex chronic disease with increasing prevalence, is characterised by reduced bone mineral density (BMD) and increased fracture risk. The high heritability of BMD suggests substantial impact of the individual genetic disposition on bone phenotypes and the development of osteoporosis. In the past years, genome-wide association studies (GWAS) identified hundreds of genetic variants associated with BMD or osteoporosis. Here, we analysed 1103 single nucleotide polymorphisms (SNPs), previously identified as associated with estimated BMD (eBMD) in the UK Biobank. We assessed whether these SNPs are related to heel stiffness index obtained by quantitative ultrasound in 5665 adult participants of the Study of Health in Pomerania (SHIP). We confirmed 45 significant associations after correction for multiple testing. Next, we analysed six selected SNPs in 631 patients evaluated for osteoporosis [rs2707518 (CPED1/WNT16), rs3779381 (WNT16), rs115242848 (LOC101927709/EN1), rs10239787 (JAZF1), rs603424 (PKD2L1) and rs6968704 (JAZF1)]. Differences in minor allele frequencies (MAF) of rs2707518 and rs3779381 between SHIP participants (higher MAF) and patients evaluated for osteoporosis (lower MAF) indicated a protective effect of the minor allele on bone integrity. In contrast, differences in MAF of rs603424 indicated a harmful effect. Co-localisation analyses indicated that the rs603424 effect may be mediated via stearoyl-CoA desaturase (SCD) expression, an enzyme highly expressed in adipose tissue with a crucial role in lipogenesis. Taken together, our results support the role of the WNT16 pathway in the regulation of bone properties and indicate a novel causal role of SCD expression in adipose tissue on bone integrity.
Target proteins in biotechnological applications are highly diverse. Therefore, versatile flexible expression systems for their functional overproduction are required. In order to find the right heterologous gene expression strategy, suitable host-vector systems, which combine different genetic circuits, are useful. In this study, we designed a novel Bacillus subtilis expression toolbox, which allows the overproduction and secretion of potentially toxic enzymes. This toolbox comprises a set of 60 expression vectors, which combine two promoter variants, four strong secretion signals, a translation-enhancing downstream box, and three plasmid backbones. This B. subtilis toolbox is based on a tailor-made, clean deletion mutant strain, which is protease and sporulation deficient and exhibits reduced autolysis and secondary metabolism. The appropriateness of this alternative expression platform was tested for the overproduction of two difficult-to-produce eukaryotic model proteins. These included the sulfhydryl oxidase Sox from Saccharomyces cerevisiae, which forms reactive hydrogen peroxide and undesired cross-linking of functional proteins, and the human interleukin-1β, a pro-inflammatory cytokine. For the best performing Sox and interleukin, overproducing and secreting variants of these new B. subtilis toolbox fermentation strategies were developed and tested. This study demonstrates the suitability of the prokaryotic B. subtilis host-vector system for the extracellular production of two eukaryotic proteins with biotechnological relevance.
Purpose
Socioeconomic factors are known to modulate health. Concerning sleep apnea, influences of income, education, work, and living in a partnership are established. However, results differ between national and ethnic groups. Results also differ between various clinical studies and population-based approaches. The goal of our study was to determine if such factors can be verified in the population of Pomerania, Germany.
Methods
A subgroup from the participants of the population-based Study of Health in Pomerania volunteered for an overnight polysomnography. Their data were subjected to an ordinal regressions analysis with age, sex, body mass index (BMI), income, education, work, and life partner as predictors for the apnea–hypopnea index.
Results
Among the subgroup (N = 1209) from the population-based study (N = 4420), significant effects were found for age, sex, and BMI. There were no significant effects for any of the socioeconomic factors.
Conclusion
Significant effects for well-established factors as age, sex, and BMI show that our study design has sufficient power to verify meaningful associations with sleep apnea. The lack of significant effects for the socioeconomic factors suggests their clinical irrelevance in the tested population.