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Background: Therapyrelated mucositis is associated with considerable morbidity. This complication following allogeneic stem cell therapy (alloSCT) is less severe after reduced intense conditioning (RIC); however, even here it may be serious. Methods: 52 patients (male: n = 35 (67%), female: n = 17 (33%)) at a median age of 62 years (35–73 years) underwent alloSCT after RIC. Conditioning was either total body irradiation (TBI)<sub>2Gy</sub>/±fludarabine (n = 33, 63.5%) or chemotherapy based. Graftversushost disease (GvHD) prophylaxis was carried out with cyclosporine A ± mycophenolate mofetil (MMF). 45 patients (87%) received shortcourse methotrexate (MTX). Mucositis was graded according to the Bearman and the World Health Organisation (WHO) scale. A variety of parameters were correlated with mucositis. Results: The Bearman and WHO scales showed excellent correlation. Mucositis was significantly more severe after chemotherapybased conditioning compared to conditioning with TBI<sub>2Gy</sub>/±fludarabine (p < 0.002) as well as in cases with an increase in creatinine levels above the upper normal value (UNV) on day +1 after SCT (p < 0.05). Furthermore, the severity correlated with time to engraftment of leucocytes (correlation coefficient (cc) = 0.26, p < 0.02) and thrombocytes (cc = 0.38, p < 0.001). Conclusions: The conditioning regimen and increased creatinine levels at day +1 were identified as factors predicting the severity of mucositis after RICSCT. Creatinine levels on day +1 after SCT may help identify patients at risk for severe mucositis in the further course of transplantation.
Background & Aim: Person-Centered-Care (PCC) requires knowledge about patient preferences. Among People living with Dementia (PlwD) only limited evidence about patient preferences, more specifically quantitative preferences, is available. Additionally, data on congruence of patient preferences with physicians’ judgements are missing. Information on patient preferences and their congruence with physicians’ judgements is expected to support Shared Decision-Making and respectively support the implementation of PCC in dementia. The aim of this dissertation was to analyze patient preferences and physicians’ judgements for PCC, including an assessment of their congruence, based on data from the mixed-methods PreDemCare-study. (Funding: Doctoral Scholarship from the Hans & Ilse Breuer-Stiftung.)
Methods: Development and conduct of a cross-sectional Analytic Hierarchy Process (AHP) survey with n=50 PlwD and n=25 physicians. Individual AHP-weights were calculated with the principal right eigenvector method and aggregated per group by Aggregation of Individual Priorities (AIP) mode. Individual consistency ratios (CRs) were calculated and aggregated per group. Group differences were analyzed descriptively by AIP-derived means and standard deviations of AHP-weights, resulting ranks, and boxplots. Additionally, differences between groups were investigated with independent paired t-tests or Mann Whitney-U tests. The sensitivity of AHP-results at the level of criteria was tested by an exclusion of inconsistent respondents in both groups, with an accepted threshold of the individual CR at ≤ 0.3 for PlwD and ≤ 0.2 for physicians.
Results: Contrary to expectation, PlwD’s and physician’s ranking of AHP-elements did not differ meaningfully. Memory Exercises was the only AHP-criterion, for which a significant difference in AHP-weights could be identified (p-value = 0.01). After inconsistent participants had been excluded, no rank reversals occurred. At the level of criteria, the mean CR for PlwD was 0.261 and 0.181 for physicians, id est (i.e.) below the
defined threshold.
Conclusion: In the selected study setting of the PreDemCare-study, patient preferences and physicians’ judgements for elements of PCC in dementia aligned well, contrary to expectations. Subject to restrictions by small sample sizes, the findings may form a basis to guide the implementation of preference-based, person-centered dementia care.
Staphylococcus aureus (S. aureus) can secrete a broad range of virulence factors, among which staphylococcal serine protease-like proteins (Spls) have been identified as bacterial allergens. The S. aureus allergen serine protease-like protein D (SplD) induces allergic asthma in C57BL/6J mice through the IL-33/ST2 signaling axis. Analysis of C57BL/6J, C57BL/6N, CBA, DBA/2, and BALB/c mice treated with intratracheal applications of SplD allowed us to identify a frameshift mutation in the serine (or cysteine) peptidase inhibitor, clade A, and member 3I (Serpina3i) causing a truncated form of SERPINA3I in BALB/c, CBA, and DBA/2 mice. IL-33 is a key mediator of SplD-induced immunity and can be processed by proteases leading to its activation or degradation. Full-length SERPINA3I inhibits IL-33 degradation in vivo in the lungs of SplD-treated BALB/c mice and in vitro by direct inhibition of mMCP-4. Collectively, our results establish SERPINA3I as a regulator of IL-33 in the lungs following exposure to the bacterial allergen SplD, and that the asthma phenotypes of mouse strains may be strongly influenced by the observed frameshift mutation in Serpina3i. The analysis of this protease-serpin interaction network might help to identify predictive biomarkers for type-2 biased airway disease in individuals colonized by S. aureus.
Background and Objective: Transcranial random noise stimulation (tRNS) is an emerging non-invasive brain stimulation technique to modulate brain function, with previous studies highlighting its considerable benefits in therapeutic stimulation of the motor system. However, high variability of results and bidirectional task-dependent effects limit more widespread clinical application. Task dependency largely results from a lack of understanding of the interaction between externally applied tRNS and the endogenous state of neural activity during stimulation. Hence, the aim of this study was to investigate the task dependency of tRNS-induced neuromodulation in the motor system using a finger-tapping task (FT) versus a go/no-go task (GNG). We hypothesized that the tasks would modulate tRNS’ effects on corticospinal excitability (CSE) and task performance in opposite directions.
Methods: Thirty healthy subjects received 10 min of tRNS of the dominant primary motor cortex in a double-blind, sham-controlled study design. tRNS was applied during two well-established tasks tied to diverging brain states. Accordingly, participants were randomly assigned to two equally-sized groups: the first group performed a simple motor training task (FT task), known primarily to increase CSE, while the second group performed an inhibitory control task (go/no-go task) associated with inhibition of CSE. To establish task-dependent effects of tRNS, CSE was evaluated prior to- and after stimulation with navigated transcranial magnetic stimulation.
Results: In an ‘activating’ motor task, tRNS during FT significantly facilitated CSE. FT task performance improvements, shown by training-related reductions in intertap intervals and increased number of finger taps, were similar for both tRNS and sham stimulation. In an ‘inhibitory’ motor task, tRNS during GNG left CSE unchanged while inhibitory control was enhanced as shown by slowed reaction times and enhanced task accuracy during and after stimulation.
Conclusion: We provide evidence that tRNS-induced neuromodulatory effects are task-dependent and that resulting enhancements are specific to the underlying task-dependent brain state. While mechanisms underlying this effect require further investigation, these findings highlight the potential of tRNS in enhancing task-dependent brain states to modulate human behavior.
Environmental activism, defined as a range of difficult pro-environmental behaviors, is analyzed within the conceptual framework of Significance Quest Theory (SQT). In Study 1, 40 interviews were carried out on two groups of people in the European Union: Committed Actors for Nature (CANs, n = 25) versus Committed Actors for Society (CASs, n = 15). Results demonstrated that Significance Quest (SQ) motivates each group to be strongly committed to their chosen action and the main difference between them being in their ideology (pro-social vs. pro-environmental). In Study 2 (N = 131), the relationship between SQ and intention to enact difficult pro-environmental behaviors was assessed. Results suggested that the higher the SQ, the higher the tendency to enact difficult pro-environmental behaviors, but not average or easy ones. Moreover, the higher the pro-environmental ideology, the stronger the indirect effect of SQ on difficult behavior through willingness to sacrifice.
Objective: We performed a pilot RCT to prove the hypothesis that a controlled ingestion of polyphenol-rich beverages (soy drink, decaffeinated black tea) in nutritive dosages by nursing women has an effect on the composition (flavonoid concentration, total antioxidant capacity) of breast milk. Methods: Healthy nursing women were supplemented with either 250 mL of a soy drink (12 mg isoflavones; n = 18), 300 mL decaffeinated black tea (67 mg catechins; n = 18), or 300 mL water (n = 8, control) for 6 days. Milk samples were collected before, during, and after intervention. Flavonoid content (isoflavones/catechins, HPLC) and total antioxidant capacity of milk and test drinks in milk specimens were assessed. Results: Isoflavone content (genistein and daidzein) in breast milk increased up to 12 nmol/L after soy drink consumption; the major flavonoids constituents of black tea (catechin, epicatechin, and respective conjugates) could not be detected in milk samples. With both interventions, the total antioxidant capacity of breast milk was not affected. Conclusions: Mothers' daily consumption of a soy drink considerably increases isoflavone content of breast milk resulting in an estimated daily exposure of 9.6 nmol isoflavones in a 4-month-old suckling infant. Luminal flavanol uptake from black tea consumed by the nursing mother may be too low to affect flavanol concentrations in breast milk.
Research has shown that parental pressure is negatively whereas parental support is positively associated with various scholastic outcomes, such as school engagement, motivation, and achievement. However, only few studies investigate boys' and girls' perception of mother and father pressure/support in detail. This might be particularly essential when it comes to girls' and boys' achievement in STEM subjects, as girls and boys might profit differently from parental pressure/support regarding their achievement in STEM and vice versa. This study aims to shed light on this topic and explores potential within—and over time associations between students' perception of parental pressure/support and grades in mathematics and biology. Using self-report data from 1,088 8th grade students at T1 (Mage = 13.70, SD = 0.53, 54% girls) from Brandenburg, Germany, multigroup cross-lagged models were conceptualized with Mplus. The results indicate that there are gender differences in the interplay of students' grades in mathematics, biology, and their perception of parental pressure and support: Whereas, mother support plays a central beneficial role for girls' achievement in STEM subjects as well as for the other parental variables over time, for boys mother support is negatively associated with math performance over time. Within-time associations further show that boys—in contrast to girls—do not benefit from any parental support regarding their performance in mathematics or biology. Finally, results suggest that the relationship between adolescents' STEM achievement and parental pressure/support is rather mono-directional than bi-directional over time.
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.
In recent years, online radicalization has received increasing attention from researchers and policymakers, for instance, by analyzing online communication of radical groups and linking it to individual and collective pathways of radicalization into violent extremism. But these efforts often focus on radical individuals or groups as senders of radicalizing messages, while empirical research on the recipient is scarce. To study the impact of radicalized online content on vulnerable individuals, this study compared cognitive and affective appraisal and visual processing (via eye tracking) of three political Internet memes (empowering a right-wing group, inciting violence against out-groups, and emphasizing unity among human beings) between a right-wing group and a control group. We examined associations between socio-political attitudes, appraisal ratings, and visual attention metrics (total dwell time, number of fixations). The results show that right-wing participants perceived in-group memes (empowerment, violence) more positively and messages of overarching similarities much more negatively than controls. In addition, right-wing participants and participants in the control group with a high support for violence directed their attention towards graphical cues of violence (e.g., weapons), differentness, and right-wing groups (e.g., runes), regardless of the overall message of the meme. These findings point to selective exposure effects and have implications for the design and distribution of de-radicalizing messages and counter narratives to optimize the efficacy of prevention of online radicalization.
Cryptochromes are evolutionary ancient blue-light photoreceptors that are part of the circadian clock in the nervous system of many organisms. Cryptochromes transfer information of the predominant light regime to the clock which results in the fast adjustment to photoperiod. Therefore, the clock is sensitive to light changes and can be affected by anthropogenic Artificial Light At Night (ALAN). This in turn has consequences for clock associated behavioral processes, e.g., diel vertical migration (DVM) of zooplankton. In freshwater ecosystems, the zooplankton genus Daphnia performs DVM in order to escape optically hunting predators and to avoid UV light. Concomitantly, Daphnia experience circadian changes in food-supply during DVM. Daphnia play the keystone role in the carbon-transfer to the next trophic level. Therefore, the whole ecosystem is affected during the occurrence of cyanobacteria blooms as cyanobacteria reduce food quality due to their production of digestive inhibitors (e.g., protease inhibitors). In other organisms, digestion is linked to the circadian clock. If this is also the case for Daphnia, the expression of protease genes should show a rhythmic expression following circadian expression of clock genes (e.g., cryptochrome 2). We tested this hypothesis and demonstrated that gene expression of the clock and of proteases was affected by ALAN. Contrary to our expectations, the activity of one type of proteases (chymotrypsins) was increased by ALAN. This indicates that higher protease activity might improve the diet utilization. Therefore, we treated D. magna with a chymotrypsin-inhibitor producing cyanobacterium and found that ALAN actually led to an increase in Daphnia’s growth rate in comparison to growth on the same cyanobacterium in control light conditions. We conclude that this increased tolerance to protease inhibitors putatively enables Daphnia populations to better control cyanobacterial blooms that produce chymotrypsin inhibitors in the Anthropocene, which is defined by light pollution and by an increase of cyanobacterial blooms due to eutrophication.