Search

To make healthy food choices, consumers need to be aware of the sugar content of foods. Units act as an environmental cue that might influence sugar content estimation accuracy. The present study (1) tested whether estimations of sugar content are more accurate in sugar cubes vs grams, (2) compared accuracy of sugar content to estimations of the foods' weight and energy content, and (3) investigated gender, education, and body mass index as potential correlates. A sample of 886 adults was randomly assigned to estimating the sugar content of 10 common foods in grams or cubes. Estimations of sugar content diverged considerably from actual values in both groups (0.22 ≤ Cohen's ds gram s ≤ 1.20; 0.20 ≤ Cohen's ds cubes ≤ 1.10), but were more pronounced for sugar content estimations in grams in 7 out of 10 foods (ts ≥ 4.04, Ps < .001, Cohen's ds ≥ 0.14). Sugar content misestimation was somewhat more pronounced than misestimation of weight (0.05 ≤ Cohen's ds ≤ 1.43) and energy content (0.04 ≤ Cohen's ds ≤ 1.19). Relationships between sugar content misestimation and gender (0.00 ≤ Cohen's ds ≤ 0.33), education (-0.07 ≤ r ≤ 0.11), and body mass index (-0.08 ≤ r ≤ 0.06) were mostly negligible. Although sugar content estimations were somewhat more accurate in sugar cubes vs grams, estimation accuracy is generally low. In addition to promoting consumers' knowledge through labeling and education, additional avenues for interventions might need to be explored for sizeable effects on food choices., Competing Interests: Author Declarations The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Radiation-induced morphea (RIM) is a rare complication of radiotherapy presenting as inflammatory fibrosis, most commonly reported in breast cancer patients. As underlying disease mechanisms are not well understood, targeted therapies are lacking. Since fibroblasts are the key mediators of all fibroproliferative diseases, this study aimed to characterize patient-derived fibroblasts to identify therapeutic targets. We studied primary human control and RIM-fibroblasts on a functional and molecular basis, analyzed peripheral blood and tissue samples and conducted, based on our findings, a treatment attempt in one patient. In RIM, we identified a distinct myofibroblast phenotype reflected by increased alpha-smooth-muscle-actin (αSMA) expression, reduced proliferation and migration rates, and overexpression of osteopontin (OPN). Our RNA sequencing identified aberrant Myc activation as a potential disease driver in RIM fibroblasts, similar to previous findings in systemic sclerosis. Treatment with the anti-inflammatory drug mesalazine reversed the myofibroblast phenotype by targeting Myc. Based on these findings, a patient with RIM was successfully treated with mesalazine, resulting in reduced inflammation and pain and tissue softening, while serum OPN was halved. The present study provides a comprehensive characterization of RIM fibroblasts, suggests a disease-driving role for Myc, demonstrates promising antifibrotic effects of mesalazine and proposes OPN as a biomarker for RIM., (© 2024. The Author(s).)

Background and Purpose: The central vein sign (CVS) is a proposed diagnostic imaging biomarker for multiple sclerosis (MS). The proportion of white matter lesions exhibiting the CVS (CVS+) is higher in patients with MS compared to its radiological mimics. Evaluation for CVS+ lesions in prior studies have been performed by manual rating, an approach that is time-consuming and has variable inter-rater reliability. Accurate automated methods would facilitate efficient assessment for CVS. The objective of this study was to compare the performance of an automated CVS detection method with manual rating for the diagnosis of MS., Materials and Methods: 3T MRI was acquired in 86 participants undergoing evaluation for MS in a 9-site multicenter study. Participants presented with either typical or atypical clinical syndromes for MS. An automated CVS detection method was employed and compared to manual rating, including total CVS+ proportion and a simplified counting method in which experts visually identified up to 6 CVS+ lesions using FLAIR* contrast (a voxel-wise product of T 2 FLAIR and post-contrast T 2 *-EPI images)., Results: Automated CVS processing was completed in 79 of 86 participants (91%), of whom 28 (35%) fulfilled the 2017 McDonald criteria at the time of imaging. The area under the receiver-operator characteristic curve (AUC) for discrimination between participants with and without MS for the automated CVS approach was 0.78 (95% confidence interval: [0.67,0.88]). This was not significantly different from simplified manual counting methods (select6*) (0.80 [0.69,0.91]) or manual assessment of total CVS+ proportion (0.89 [0.82,0.96]). In a sensitivity analysis excluding 11 participants whose MRI exhibited motion artifact, the AUC for the automated method was 0.81 [0.70,0.91], which was not statistically different from that for select6* (0.79 [0.68,0.92]) or manual assessment of total CVS+ proportion (0.89 [0.81,0.97])., Conclusions: Automated CVS assessment was comparable to manual CVS scoring for differentiating patients with MS from those with other diagnoses. Large, prospective, multicenter studies utilizing automated methods and enrolling the breadth of disorders referred for suspicion of MS are needed to determine optimal approaches for clinical implementation of an automated CVS detection method., Abbreviations: CVS= central vein sign; CVS+ = white matter lesions exhibiting the CVS; MRI = magnetic resonance imaging; MS = multiple sclerosis; T 2 FLAIR = T 2 fluid-attenuated inversion recovery; T 2 *-EPI = T 2 *-weighted 3D echo planar imaging; FLAIR* = a voxel-wise product of T 2 FLAIR and post-contrast T 2 *-EPI images; select6* = simplified counting method in which experts visually identified up to 6 CVS+ lesions on FLAIR* imaging., Competing Interests: Disclosures: D.S. Reich’s lab has received research support from Abata Therapeutics and Sanofi-Genzyme. A.J. Solomon reports consulting or advisory board compensation for Octave Bioscience, TG Therapeutics, Kiniksa Pharmaceuticals, Genentech, and Horizon Therapeutics, non-promotional speaking for EMD Serono, contracted research for Sanofi, Actelion, Genentech/Roche, Novartis, and research funding from Bristol Meyers Squibb., (© 2024 by American Journal of Neuroradiology.)

Background: Fortunately, the majority of COVID-19 patients recover from olfactory dysfunction (OD) within the first couple of weeks. However, from approximately 5% up to 20% continue to suffer from OD even more than 1 year after the onset. Nonetheless, factors associated with long-lasting OD are hardly known. The aim of this study was to identify favourable and disadvantageous markers of persisting OD in COVID-19 patients., Methodology: Sixty-six patients (46 female; mean age: 39.9 years) that suffer from OD longer than 6 months due to laboratory-confirmed SARS-CoV-2 infection have participated in this longitudinal study. Participants completed comprehensive psychophysical chemosensory tests (i.e., Sniffin' Sticks = TDI) and questionnaires twice at our department-on average 219 ± 80 (T-1) and 489 ± 89 (T-2) days after the onset of symptoms, respectively. Olfactory recovery rates were associated with demographic factors and questionnaires using linear regression analysis., Results: Patients below 40 years of age improved better (TDI: 4.1 ± 4.3 vs. 0.7 ± 5.8; p = 0.008) and achieved statistically significant higher scores (TDI: 31.5 ± 4.0 vs. 27.3 ± 6.7; p = 0.033) regarding psychophysical chemosensory tests. Furthermore, linear regression analysis revealed that parosmia was associated with worse orthonasal smell function (T-1: β = -0.346, p = 0.004; T-2: β = -0.384, p = 0.001), especially concerning identification subtest (T-1: β = -0.395, p = 0.001; T-2: β = -0.398, p < 0.001). Moreover, increasing parosmia between T-1and T-2 led to worse orthonasal olfactory function (β = -0.294, p = 0.016)., Conclusions: Older age and parosmia seem to be unfavourable factors of persisting OD in COVID-19 patients., (© 2024 The Author(s). Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799&#95;1810delinsATG, p.(V600&#95;W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies., (© 2024. The Author(s).)

Objectives: The aim of the present study was to follow the daily course of patients with olfactory dysfunction and healthy controls and to assess (i) how many times a day, (ii) at which time, and (iii) in which aspect of daily life participants are conscious about their sense of smell., Methods: In this longitudinal study, 49 patients with smell loss and 30 healthy participants were enrolled. Olfactory function was assessed using the Sniffin' Sticks. All participants received paper diaries designed for a 14-day period, featuring 12 rows representing 12 daily hours and six columns for various daily life aspects. They were instructed to mark their awareness of smell by indicating the relevant row and column in the diary. Following the return of the diaries, a second olfactory test was conducted within the patient group., Results: On average, patients were consciously aware of their sense of smell around 8 times daily, while healthy participants noted it about 6.5 times a day. Both groups primarily focused on their sense of smell during activities related to "eating," followed by considerations in "social life" and "personal hygiene." Interestingly, distinct patterns emerged: patients peaked in awareness at 8 a.m. and 7 p.m., whereas healthy individuals showed peaks at 6 a.m., 12 p.m., and 7 p.m. Despite regular diary use, we observed no improvement in patients' olfactory function or related quality of life., Conclusion: The olfactory diary is a valuable tool unveiling individual smell awareness patterns in patients with smell loss, aiding in counseling and patient management., Level of Evidence: 4., Competing Interests: The authors declare that there are no conflicts of interests regarding the publication of this article., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Numerous smartphone apps are targeting physical activity (PA) and healthy eating (HE), but empirical evidence on their effectiveness for the initialization and maintenance of behavior change, especially in children and adolescents, is still limited. Social settings influence individual behavior; therefore, core settings such as the family need to be considered when designing mobile health (mHealth) apps., Objective: The purpose of this study was to evaluate the effectiveness of a theory- and evidence-based mHealth intervention (called SMARTFAMILY [SF]) targeting PA and HE in a collective family-based setting., Methods: A smartphone app based on behavior change theories and techniques was developed, implemented, and evaluated with a cluster randomized controlled trial in a collective family setting. Baseline (t 0 ) and postintervention (t 1 ) measurements included PA (self-reported and accelerometry) and HE measurements (self-reported fruit and vegetable intake) as primary outcomes. Secondary outcomes (self-reported) were intrinsic motivation, behavior-specific self-efficacy, and the family health climate. Between t 0 and t 1 , families of the intervention group (IG) used the SF app individually and collaboratively for 3 consecutive weeks, whereas families in the control group (CG) received no treatment. Four weeks following t 1 , a follow-up assessment (t 2 ) was completed by participants, consisting of all questionnaire items to assess the stability of the intervention effects. Multilevel analyses were implemented in R (R Foundation for Statistical Computing) to acknowledge the hierarchical structure of persons (level 1) clustered in families (level 2)., Results: Overall, 48 families (CG: n=22, 46%, with 68 participants and IG: n=26, 54%, with 88 participants) were recruited for the study. Two families (CG: n=1, 2%, with 4 participants and IG: n=1, 2%, with 4 participants) chose to drop out of the study owing to personal reasons before t 0 . Overall, no evidence for meaningful and statistically significant increases in PA and HE levels of the intervention were observed in our physically active study participants (all P>.30)., Conclusions: Despite incorporating behavior change techniques rooted in family life and psychological theories, the SF intervention did not yield significant increases in PA and HE levels among the participants. The results of the study were mainly limited by the physically active participants and the large age range of children and adolescents. Enhancing intervention effectiveness may involve incorporating health literacy, just-in-time adaptive interventions, and more advanced features in future app development. Further research is needed to better understand intervention engagement and tailor mHealth interventions to individuals for enhanced effectiveness in primary prevention efforts., Trial Registration: German Clinical Trials Register DRKS00010415; https://drks.de/search/en/trial/DRKS00010415., International Registered Report Identifier (irrid): RR2-10.2196/20534., (©Kathrin Wunsch, Janis Fiedler, Sebastian Hubenschmid, Harald Reiterer, Britta Renner, Alexander Woll. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 26.04.2024.)

The small molecule A-485 competitively inhibits the histone acetyltransferase domain of CBP (cyclic-adenosine monophosphate response element-binding protein)/p300. Apart from its antineoplastic activity, researchers are exploring its potential benefits in treating osteoporosis and its impact on energy metabolism. However, so far, only limited pharmacokinetic data are available, and the crucial determination of A-485 concentration in various biological materials with small sample volumes remains unpublished. A rapid and sensitive LC-tandem mass spectrometry method has been developed and validated to quantify A-485 in mouse serum and tissue. In this method, serum samples underwent precipitation with acetonitrile, while cell lysates were appropriately diluted. The determination of A-485 utilized a reversed-phase column with a mobile phase gradient, and detection was carried out in multiple reaction monitoring mode. The lower standard sample, with a concentration of 7.8 ng/mL, served as the lower limit of quantification, while the upper standard was established at 1000 ng/mL. A-485 concentrations were assessed in both serum samples and the lysate of all examined tissues, revealing swift metabolic clearance. The analytical method outlined here is deemed appropriate for subsequent studies. The ability to measure the active ingredient in various compartments facilitates the determination of accurate pharmacokinetic parameters. In the event of human use of A-485, the analysis method can be seamlessly transferred to human samples., (© 2023 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd.)

Background: The direct thrombin inhibitor argatroban is indicated for the treatment of heparin-induced thrombocytopenia II, but it is also used off-label to treat critically ill patients presenting with heparin resistance, severe antithrombin deficiency, or hypercoagulability. Direct drug monitoring is not routinely available, and argatroban dosing is mainly based on global coagulation assays such as activated partial thromboplastin time (PTT) or diluted thrombin time (TT), both of which have limitations in patients with hypercoagulability., Methods: Blood samples were obtained from critically ill patients treated with argatroban. Activated PTT and diluted TT were measured with a STA R Max3 analyzer (STAGO Deutschland GmbH, Germany) using an argatroban-calibrated kit. Ecarin clotting time was measured using a point-of-care viscoelastic test device. Liquid chromatography with tandem mass spectrometry was performed using a reversed-phase column, a solvent gradient, and an API4000 mass spectrometer with electrospray. Correlation was described using Pearson correlation coefficient r and Bayesian multilevel regression to estimate relationships between outcomes and covariates., Results: From June 2021 to March 2022, 205 blood samples from 22 patients were analyzed, allowing for 195 activated PTT-liquid chromatography with tandem mass spectrometry comparisons, 153 ecarin clotting time-liquid chromatography with tandem mass spectrometry comparison, and 105 diluted TT-liquid chromatography with tandem mass spectrometry comparisons. Compared to liquid chromatography with tandem mass spectrometry, performance of argatroban quantification was best for diluted TT (r = 0.91), followed by ecarin clotting time (r = 0.58) and activated PTT (r = 0.48). Regression analysis revealed that patients with sepsis were more prone to argatroban overdosing (coefficient, 4.194; 95% credible interval, 2.220 to 6.792)., Conclusions: Although activated PTT monitoring of argatroban is the most commonly used test, in critically ill patients, diluted TT provides more precise measurements. Alternately, point-of-care viscoelastic ecarin clotting time also provides guidance for argatroban dosing to identify overdosing if available. The data also suggested that patients with sepsis are at greater risk for argatroban overdosing., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Context: Overweight and obesity have become a major health burden with a higher prevalence of obesity in women than in men. Mental stress has been discussed to play a role in this context., Objective: We investigated endocrine mechanisms underlying eating after acute psychosocial stress and potential sex differences therein., Methods: A total of 32 male and 31 female healthy participants underwent the Trier Social Stress Test before they tasted ice cream in a bogus taste test 15 minutes after stress. We repeatedly assessed the stress hormone cortisol and the satiety hormone cholecystokinin (CCK) in saliva as well as perceived hunger before and up to 1 hour after stress., Results: Lower immediate total cortisol stress reactivity predicted higher hunger (Ps ≤ .004), but was not associated with food intake (Ps ≥ .90) or total CCK release (Ps ≥ .84). As compared to men, women ate less after stress (Ps < .001) and had consistently lower levels of hunger (Ps ≤ .024) and cortisol (Ps ≤ .008) as well as a lower immediate total cortisol stress reactivity (Ps = .002). Further, they differed in the kinetics of CCK over the total experimental procedure (Ps ≤ .011), in immediate reaction to stress (Ps ≤ .038), and after eating (Ps ≤ .072), with women's CCK levels continuously decreasing while men's CCK levels were reactive., Conclusion: We found evidence for lower immediate total cortisol stress reactivity relating to higher perceived hunger, with lower cortisol levels in women. Unlike in men, CCK levels in women were not reactive to acute stress and eating and decreased continuously. Our results may suggest a higher risk for stress-induced eating in women., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Molecular biological methods have emerged as inevitable tools to accompany the process of cell line development for the generation of stable and highly productive manufacturing cell lines in the biopharmaceutical industry. PCR-based methods are especially useful for screening and characterization of cell lines due to their low cost, scalability, precision and propensity for multidimensional read-outs. In this study, the diverse applications of droplet digital PCR (ddPCR) as a molecular biological tool for cell line development are demonstrated. Specifically, it is shown that ddPCR can be used to enable precise, sensitive and reproducible absolute quantification of genomically integrated transgene copies during cell line development and cell bank characterization. Additionally, an amplitude multiplexing approach is applied to simultaneously run multiple assays on different genetic targets in a single reaction and advance clonal screening by measuring gene expression profiles to predict the assembly and homogeneity of difficult-to-express (DTE) proteins. The implementation of ddPCR-based assays during cell line development allows for early screening at a transcriptional level, particularly for complex, multidomain proteins, where balanced polypeptide chain ratios are of primary importance. Moreover, it is demonstrated that ddPCR-based genomic characterization improves the robustness, efficiency and comparability of absolute transgene copy number quantification, an essential genetic parameter that must be demonstrated to regulatory authorities during clinical trial and market authorization application submissions to support genetic stability and consistency of the selected cell substrate., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest to exist for any of the work published in this manuscript. All authors are employees of Boehringer Ingelheim, which sells pharmaceuticals., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The European and Japanese system for cholesteatoma classification proposed an anatomical differentiation in five sites. In stage I disease, one site would be affected and in stage II, two to five. We tested the significance of this differentiation by analyzing the influence of the number of affected sites on residual disease, hearing ability and surgical complexity., Methods: Cases of acquired cholesteatoma treated at a single tertiary referral center between 2010-01-01 and 2019-07-31 were retrospectively analyzed. Residual disease was determined according to the system. The air-bone gap mean of 0.5, 1, 2, 3 kHz (ABG) and its change with surgery served as hearing outcome. The surgical complexity was estimated regarding the Wullstein's tympanoplasty classification and the procedure approach (transcanal, canal up/down)., Results: 513 ears (431 patients) were followed-up during 21.6 ± 21.5 months. 107 (20.9%) ears had one site affected, 130 (25.3%) two, 157 (30.6%) three, 72 (14.0%) four and 47 (9.2%) five. An increasing number of affected sites resulted in higher residual rates (9.4-21.3%, p = 0.008) and surgical complexity, as well poorer ABG (preoperative 14.1 to 25.3 dB, postoperative 11.3-16.8 dB, p < 0.001). These differences existed between the means of cases of stage I and II, but also when only considering ears with stage II classification., Conclusion: The data showed statistically significant differences when comparing the averages of ears with two to five affected sites, questioning the pertinence of the differentiation between stages I and II., (© 2023. The Author(s).)

B cell-targeted therapies are effective for treating multiple different kidney diseases in humans and also protect mice from Adriamycin nephropathy. Because glomerular IgM is frequently seen in both humans and mice with "nonimmune" forms of glomerular disease, we hypothesized that natural IgM binds to epitopes displayed in the injured glomerulus, exacerbating injury. To test this hypothesis, we induced Adriamycin nephropathy in BALB/C mice that cannot secrete soluble IgM (sIgM-/- mice) and compared them with BALB/C controls. Contrary to our prediction, we found that female sIgM-/- mice developed higher mortality and more severe kidney injury after injection of Adriamycin. The absence of soluble IgM did not reduce glomerular complement activation, and IgG was seen deposited within the injured glomeruli. Furthermore, we discovered that female sIgM-/- mice have higher levels of anti-cardiolipin IgG, and that IgG from these mice binds to epitopes in the injured kidney. These findings indicate that natural IgM may prevent generation of autoreactive IgG. Circulating levels of anti-cardiolipin IgG decreased after induction of kidney injury in female mice, consistent with deposition of the Abs in injured tissues. Better understanding of the mechanisms by which the immune system modulates and amplifies kidney injury may enable the development of targeted therapies to slow kidney disease progression., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Nearly all approaches to personalized nutrition (PN) use information such as the gene variants of individuals to deliver advice that is more beneficial than a generic "1-size-fits-all" recommendation. Despite great enthusiasm and the increased availability of commercial services, thus far, scientific studies have only revealed small to negligible effects on the efficacy and effectiveness of personalized dietary recommendations, even when using genetic or other individual information. In addition, from a public health perspective, scholars are critical of PN because it primarily targets socially privileged groups rather than the general population, thereby potentially widening health inequality. Therefore, in this perspective, we propose to extend current PN approaches by creating adaptive personalized nutrition advice systems (APNASs) that are tailored to the type and timing of personalized advice for individual needs, capacities, and receptivity in real-life food environments. These systems encompass a broadening of current PN goals (i.e., what should be achieved) to incorporate "individual goal preferences" beyond currently advocated biomedical targets (e.g., making sustainable food choices). Moreover, they cover the "personalization processes of behavior change" by providing in situ, "just-in-time" information in real-life environments (how and when to change), which accounts for individual capacities and constraints (e.g., economic resources). Finally, they are concerned with a "participatory dialog between individuals and experts" (e.g., actual or virtual dieticians, nutritionists, and advisors) when setting goals and deriving measures of adaption. Within this framework, emerging digital nutrition ecosystems enable continuous, real-time monitoring, advice, and support in food environments from exposure to consumption. We present this vision of a novel PN framework along with scenarios and arguments that describe its potential to efficiently address individual and population needs and target groups that would benefit most from its implementation., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Significance Statement: Histologic quantification of complement C3 deposits in kidney biopsies provides prognostic information in patients with glomerulonephritis. Unfortunately, kidney biopsies are invasive procedures that cannot be performed regularly and only provide a snapshot of a small portion of one kidney at the time of sampling. We have developed a method to noninvasively detect specific C3 fragment deposition throughout both kidneys, using a monoclonal antibody targeting tissue-bound iC3b/C3d linked to a bioluminescent resonance energy transfer construct that emits near-infrared light. In a mouse model of glomerulonephritis, the probe detected iC3b/C3d in kidneys of live mice by bioluminescent imaging. This demonstrates that noninvasive imaging with an anti-iC3b/C3d probe can be used to monitor inflammation in the kidneys., (Copyright © 2023 by the American Society of Nephrology.)

Analysis of illicit drugs, medicines, and pathogens in wastewater is a powerful tool for epidemiological studies to monitor public health trends. The aims of this study were to (i) assess spatial and temporal trends of population-normalized mass loads of illicit drugs and nicotine in raw wastewater in the time of regulations against SARS-CoV-2 infections (2020-21) and (ii) find substances that are feasible markers for characterizing the occurrence of selected drugs in wastewater. Raw sewage 24-h composite samples were collected in catchment areas of 15 wastewater treatment plants (WWTPs) in urban, small-town, and rural areas in Germany during different lockdown phases from April 2020 to December 2021. Parent substances (amphetamine, methamphetamine, MDMA, carbamazepine, gabapentin, and metoprolol) and the metabolites of cocaine (benzoylecgonine) and nicotine (cotinine) were measured. The daily discharge of WWTP influents were used to calculate the daily load (mg/day) normalized by population equivalents (PE) in drained catchment areas (in mg/1,000 persons/day). A weekend trend for illicit drugs was visible with higher amounts on Saturdays and Sundays in larger WWTPs. An influence of the regulations to reduce SARS-CoV-2 infections such as contact bans and border closures on drug consumption has been proven in some cases and refuted in several. In addition, metoprolol and cotinine were found to be suitable as marker substances for the characterization of wastewater. A change in drug use was visible at the beginning of the SARS-CoV-2 crisis. Thereafter from mid-2020, no obvious effect was detected with regard to the regulations against SARS-CoV-2 infections on concentration of drugs in wastewater. Wastewater-based epidemiology is suitable for showing changes in drug consumption during the COVID-19 lockdown., (© 2023. The Author(s).)

The natural monoclonal antibody B4-IgM recognizes murine annexin 4 (mAn4) and exacerbates ischemia-reperfusion injury in many mouse models. During apoptosis, the intracellular mAn4 protein translocates to the membrane surface, remaining attached to the outer membrane leaflet where it is recognized by the anti-mAn4 B4-IgM antibody. B4-IgM does not recognize human annexin 4 (hAn4). However, the B4-IgM antibody epitope was detected by Western blot of unknown human proteins and by flow cytometry on all studied human cell lines undergoing apoptosis and on a minor subset of healthy cells. The B4-IgM antibody also recognizes the epitope on necrotic cells in cytoplasmic proteins, apparently entering through pores large enough to allow natural antibodies to penetrate the cells and bind to the epitope expressed on self-proteins. Using proteomics and site-directed mutagenesis, we found that B4-IgM binds to an epitope with post-translationally modified acetylated N-terminal methionine, followed by either glutamic or aspartic acid. The epitope is not induced by apoptosis or injury because this modification can also occur during protein translation. This finding reveals an additional novel mechanism whereby injured cells are detected by natural antibodies that initiate pathogenic complement activation through the recognition of epitopes that are shared across multiple proteins found in variable cell lines., (Copyright © 2023. Published by Elsevier Ltd.)

From 2014 to 2022, the BMBF has funded five research networks in prevention research and health promotion that are also jointly coordinated (Research Network Primary Prevention and Health Promotion, www.fp2g.net). The researchers have produced a large number of relevant research outputs with insights gained into essential aspects of prevention research and health promotion. The networks research focused on basic principles, application-relevant findings, and implementation conditions of long-term prevention and health promotion for non-communicable diseases (NCDs). The constraints imposed by the pandemic from 2020 onwards were partly addressed by integrating Corona-related research and transfer activities. The importance of resilience for dealing with multiple health and social challenges got increased attention and was analyzed and discussed during the pandemic. For prevention research, research questions such as how to better implement prevention measures through digital tools are gaining additional importance. Together, the research networks have presented achievements and desiderata for future research. This perspective paper with its nine theses formulated in conclusion is intended as a stimulus for discussion among funders as well as the communty of researchers on the subject of successful prevention and health promotion. It is explicitly part of the continuity of the memoranda on prevention research developed in 2012., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: To evaluate potential interactions and compensatory mechanisms of subjectively impaired taste function with ortho- and retronasal olfaction after glossectomy., Study Design: In this cross-sectional pilot study, chemosensory functions were assessed in 25 patients with tongue carcinomas after glossectomy. The orthonasal-, retronasal-, and gustatory functions were tested with a mean time of 25 months after surgery with the Sniffin' Sticks odor identification test kit (ISST), the Candy Smell-27 test (CST-27) and the Taste strip test (TST). Visual analog scales (VAS) were additionally used for self-assessment of taste, flavor perception, and odor ranging from 0 (no perception) to 10 (excellent perception) and further correlated with our psychophysical evaluated outcome measures., Results: The TST, ISST, and CST-27 tests revealed that only eight (32%) and 13 (52%) glossectomy patients had normal taste and orthonasal function, e 21 (84%) patients showed normal retronasal function. Importantly, neither extent of resection and reconstruction nor prior radiotherapy affected chemosensory functions. Contrary, 20 (80%) patients rated their taste and flavor perception as acceptable (VAS >5). Results of the TST, ISST, and CST-27 tests did not correlate with the equivalent self-assessments of taste (p = 0.260, r = 0.234), odor (p = 0.588, r = -0.114), and flavor (p = 0.728, r = 0.073) perception., Conclusion: There was a significant discrepancy between self-perception of taste and flavor and assessed gustatory function after glossectomy. A contribution of the intact retronasal olfactory system could be a possible explanation of our results., Level of Evidence: 4 Laryngoscope, 133:375-382, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Wastewater-based epidemiology provides a conceptual framework for the evaluation of the prevalence of public health related biomarkers. In the context of the Coronavirus disease-2019, wastewater monitoring emerged as a complementary tool for epidemic management. In this study, we evaluated data from six wastewater treatment plants in the region of Saxony, Germany. The study period lasted from February to December 2021 and covered the third and fourth regional epidemic waves. We collected 1065 daily composite samples and analyzed SARS-CoV-2 RNA concentrations using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Regression models quantify the relation between RNA concentrations and disease prevalence. We demonstrated that the relation is site and time specific. Median loads per diagnosed case differed by a factor of 3-4 among sites during both waves and were on average 45 % higher during the third wave. In most cases, log-log-transformed data achieved better regression performance than non-transformed data and local calibration outperformed global models for all sites. The inclusion of lag/lead time, discharge and detection probability improved model performance in all cases significantly, but the importance of these components was also site and time specific. In all cases, models with lag/lead time and log-log-transformed data obtained satisfactory goodness-of-fit with adjusted coefficients of determination higher than 0.5. Back-estimation of testing efficiency from wastewater data confirmed state-wide prevalence estimation from individual testing statistics, but revealed pronounced differences throughout the epidemic waves and among the different sites., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests that could influence this study. Ethics application (BO-EK-383072021) has been confirmed by the Ethic Committee of Technische Universität Dresden, which is registered as institutional review board (IRB00001473) at the Office of Human Research Protection., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Complement activation at a particular location is determined by the balance of activating and inhibitory proteins. Factor H is a key regulator of the alternative pathway of complement, and genetic or acquired impairments in Factor H are associated with glomerular injury. The human Factor H-related proteins (FHRs) comprise a family of five proteins that are structurally related to Factor H. Variations in the genes or expression levels of the FHRs are also associated with glomerular disease, although the mechanisms of glomerular protection/injury are incompletely understood. To explore the role of the FHRs on complement regulation/dysregulation in the kidney, we expressed and purified recombinant murine FHRs (FHRs A, B, C and E). These four distinct FHRs contain binding regions with high amino acid sequence homology to binding regions within Factor H, but we observed different interactions of the FHRs with Factor H binding ligands, including heparin and C3d. There was differential binding of the FHRs to the resident kidney cell types (mesangial, glomerular endothelial, podocytes, and tubular epithelial). All four FHRs caused complement dysregulation on kidney cell surfaces in vitro, although the magnitude of the effect differed among the FHRs and also varied among the different kidney cells. However, only FHR E caused glomerular complement dysregulation when injected in vivo but did not exacerbate injury when injected into mice with ischemic acute kidney injury, an alternative pathway-mediated model. Thus, our experiments demonstrate that the FHRs have unique, and likely context-dependent, effects on the different cell types within the kidney., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Dependent on the excretion pattern, wastewater monitoring of viruses can be a valuable approach to characterizing their circulation in the human population. Using polyethylene glycol precipitation and reverse transcription-quantitative PCR, the occurrence of RNA of SARS-CoV-2 and influenza viruses A/B in the raw wastewater of two treatment plants in Germany between January and May 2022 was investigated. Due to the relatively high incidence in both exposal areas (plant 1 and plant 2), SARS-CoV-2-specific RNA was determined in all 273 composite samples analyzed (concentration of E gene: 1.3 × 10 4 to 3.2 × 10 6 gc/L). Despite a nation-wide low number of confirmed infections, influenza virus A was demonstrated in 5.2% (concentration: 9.8 × 10 2 to 8.4 × 10 4 gc/L; plant 1) and in 41.6% (3.6 × 10 3 to 3.0 × 10 5 gc/L; plant 2) of samples. Influenza virus B was detected in 36.0% (7.2 × 10 2 to 8.5 × 10 6 gc/L; plant 1) and 57.7% (9.6 × 10 3 to 2.1 × 10 7 gc/L; plant 2) of wastewater samples. The results of the study demonstrate the frequent detection of two primary respiratory viruses in wastewater and offer the possibility to track the epidemiology of influenza by wastewater-based monitoring.

BRAFV600 mutations in melanoma are targeted with mutation-specific BRAF inhibitors in combination with MEK inhibitors, which have significantly increased overall survival, but eventually lead to resistance in most cases. Additionally, targeted therapy for patients with NRASmutant melanoma is difficult. Our own studies showed that BRAF inhibitors amplify the effects of MEK inhibitors in NRASmutant melanoma. This study aimed at identifying a BRAF and MEK inhibitor combination with superior anti-tumor activity to the three currently approved combinations. We, thus, assessed anti-proliferative and pro-apoptotic activities of all nine as well as resistance-delaying capabilities of the three approved inhibitor combinations in a head-to-head comparison in vitro. The unconventional combination encorafenib/trametinib displayed the highest activity to suppress proliferation and induce apoptosis, acting in an additive manner in BRAFmutant and in a synergistic manner in NRASmutant melanoma cells. Correlating with current clinical studies of approved inhibitor combinations, encorafenib/binimetinib prolonged the time to resistance most efficiently in BRAFmutant cells. Conversely, NRASmutant cells needed the longest time to establish resistance when treated with dabrafenib/trametinib. Together, our data indicate that the most effective combination might not be currently used in clinical settings and could lead to improved overall responses.

Background: Migraine shows a cyclic pattern with an inter-ictal-, a pre-ictal, an ictal- and a post-ictal phase. We aimed to examine changes in psychophysical parameters during the migraine cycle., Methods: The perception of nociceptive and non-nociceptive stimuli and an electrically induced axon-reflex-erythema were assessed in 20 healthy controls and 14 migraine patients on five consecutive days according to different phases of the migraine cycle. Pain was rated three times during a 10-second electrical stimulus. The size of the axon-reflex-erythema was determined using laser-Doppler-imaging. Intensity and hedonic estimates of odours presented by Sniffin' Sticks were rated., Results: In healthy controls, no significant changes over the test days were observed. In migraine patients pain thresholds at the head decreased with an ictal minimum. Less habituation after five seconds of stimulation at the head was found pre-ictally, whereas reduced habituation to 10-second electrical stimulation was present in all phases. The axon-reflex-erythema size showed an inter-ictal-specific minimum at the head. odours were perceived ictally as more unpleasant and intense., Conclusions: Somatosensory functions, pain thresholds and habituation as predominantly central parameters, axon-reflex-erythema as a peripheral function of trigeminal neurons and odour perception as a predominantly extra-thalamic sensation change specifically over the migraine cycle indicating complex variations of neuronal signal processing.

Background: In times of unprecedented infectious disease threats, it is essential to understand how to increase individual protective behaviors and support for collective measures. The present study therefore examines factors associated with individual and collective pathways., Methods: Data was collected through an online survey from 4483 participants (70.8% female, M = 41.2 years) across 10 countries from April 15, 2020 to June 2, 2020 as part of the "EUCLID" project (https://euclid.dbvis.de). Structural equation modeling was used to examine individual and collective pathways across and within countries., Results: Overall, the adoption of individual protective behaviors and support for collective measures were high. Risk perception on the individual level and perceived effectiveness at the collective level were positively associated with both individual protective behaviors and support for collective measures. Furthermore, the model explained considerable variance in individual (40.7%) and collective protective behaviors (40.8%) and was largely replicated across countries., Conclusions: The study extends previous research by demonstrating that individual risk perception and perceived effectiveness of collective measures jointly affect individual protective health behaviors and support for collective measures. These findings highlight the need to jointly consider a variety of behavioral actions against infectious disease threats, acknowledging interactions between individual and collective pathways., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The present study aimed to investigate how often and to what degree older adults living in an area of Gujarat, Western India, enact traditional and modern eating behaviors. Specifically, we aimed to determine which facets of traditional eating are enacted rarely and which facets of modern eating are enacted often. Moreover, we hypothesized that urban older adults show a higher level of modern eating behaviors than rural older adults. Furthermore, we examined which traditional eating behaviors are more prevalent in rural older adults, and which are more prevalent in urban older adults., Methods: A trained research assistant administered a questionnaire in a face-to-face situation with 120 older adults in a rural and an urban area of Gujarat, Western India. Participants were asked how often and to what degree they perform 57 traditional and modern eating behaviors., Results: Overall, our sample of older Gujaratis reported a high level of traditional eating behaviors and a low level of modern eating behaviors. However, we also found, for example, a low level of the traditional eating facet of men getting preferential treatment and a high level of the modern eating facet of food being readily available. Moreover, most modern eating facets were more pronounced in the urban than in the rural sample. This was also the case for half of all traditional eating facets., Conclusion: Our sample of older adults living in an area of Gujarat displayed more modern eating behaviors in urban than in rural areas. At the same time, however, the urban sample showed also more traditional eating behaviors, such as eating more fruits, possibly because of better food availability. Altogether, results might hint at some signs of modernization among older adults in this area of Gujarat with regard to changing gender roles and better food availability., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Food cultures can play a role in health and well-being. This raises the questions of whether nation boundaries unite the food cultures of different regions and ethnic groups, what characterises food cultures from very different parts of the world, and what similarities and differences exist. The present study aimed to investigate these questions with regard to eating traditions and modern eating practices. In this cross-sectional study, we recruited 3722 participants from ten countries - Brazil, China, France, Germany, Ghana, India, Japan, Mexico, Turkey, and the USA. Participants represented 25 regional and ethnic groups. They were queried about 86 traditional and modern facets of their food cultures in interviews, paper-pencil and online questionnaires. First, hierarchical cluster analysis suggested nine distinct clusters of food cultures - the food cultures of the Brazilian, Chinese, Ghanaian, Indian, Japanese, Mexican, Turkish, African and Latin US American samples, and of European descendants. Interestingly, for seven of the ten investigated countries, nation boundaries united food cultures. Second, each of the nine food culture clusters was characterised by a unique pattern of traditional and modern eating practices. Third, the nine food culture clusters varied more in their traditional eating practices than their modern eating practices. These results might promote a better understanding of the link between food cultures and health and well-being that goes beyond nutrients. For instance, food cultures might be linked to well-being via strengthening people's sense of cultural identity. Moreover, the present results contribute to a better understanding of the complex interplay between food and culture, and could help in developing culturally competent interventions to improve diet and reduce the risk of eating-related diseases., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Olfactory dysfunction (OD) is a common symptom of Coronavirus Disease 2019 (COVID-19). Although many patients have been reported to regain olfactory function within the first month, long-term observation reports vary. Therefore, we aimed to assess the course of chemosensory function in patients diagnosed with COVID-19 within 3-15 months after the infection., Methods: One hundred and two patients (71 females and 31 males; mean age 38.8 years) diagnosed with laboratory-confirmed COVID-19 and subjective OD participated in this single-center study 111-457 days after onset of OD. Patients first performed chemosensory tests at home, followed by psychophysical testing (Sniffin' Sticks (TDI), 27-item Candy Smell Test (CST), Taste Strips Test (TST)) in the clinic. Questionnaires regarding importance of olfaction (IOQ) and olfactory-specific quality of life (QOD) were applied at both timepoints., Results: After a mean 216 days (SD 73; range 111-457) between OD onset and follow-up testing, the mean Sniffin' Sticks (TDI) score was 27.1 points (SD 5.8; range 4.25-38.5): 4.0% were anosmic, 72.5% hyposmic, and 23.5% normosmic. At follow-up testing, 73.5% of patients reported improvement, 5.9% deterioration, and 20.6% no change in OD. Moreover, full recovery of self-perceived smell, flavor, and taste was not observed. According to questionnaires, the individual importance of smell did not change, but participants showed improvement in OD-related quality of life (p < 0.001) and had increased parosmia scores (p = 0.014) at follow-up., Conclusion: Our results show that long-lasting OD after SARS-CoV-2 infection is a common symptom. The majority of patients had OD in the range of hyposmia, which was confirmed by comprehensive smell tests., (© 2021. The Author(s).)

Objective: To develop an olfactory test that can be conducted by an untrained person using common household items and to introduce a German version of the Chemosensory Pleasure Scale for Children (CPS-C(de))., Methodology: This olfactory home test was developed in phases including evaluation of odors for suitability in a home setting. Parents of 50 children (ages 6-17) were then equipped with instruction manuals and participants were tested twice in a cross-over design. A validated pediatric olfactory test (the Universal Sniff test (U-Sniff)) served as the comparative gold standard. Additionally, a Chinese-English-German "back-and-forth" translation was conducted to establish the CPS-C(de) and was tested for empirical validity., Results: Fourteen items were tested for feasibility, and all were identified on a sufficient rate (≥66%, mean ± SD of 93.3% ± 9.5%). Bland Altman Plot analysis between home testing and the U-Sniff test was nearly identical (bias = 0.04). CPS-C(de) showed similar results to the original Chinese version and a moderate correlation was found between CPS-C(de) scores and Body Mass Index of children (r 30  = -0.527, p = 0.003)., Conclusions: Remote olfactory testing in children using household items is feasible. The CPS-C(de) may be of value for future olfactory studies., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The present study examined the relationship between risk experience and risk perceptions in relation to the target (risk to the self vs. others) and for two different types of risk: acute risks (i.e., terrorist attacks) and cumulative health risks (i.e., alcohol consumption, tobacco consumption, and unhealthy eating) in two countries (Israel and Germany). An online survey (N = 571) was conducted to assess participants' previous personal experience with acute and cumulative risks and their personal and general risk perceptions. The results showed that personal experience with terrorism was related to increased personal and general risk perceptions, while personal experience with cumulative health risks was related to increased personal but not general risk perceptions. It is argued that an increase in risk perception with more risk experience can be explained by the amount of available information about people's personal as well as other people's risk status. The findings emphasize that the experience-risk perception relationship depends on the target of the risk and the type of risk experience., (© 2021 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Many people worldwide use plant preparations for medicinal purposes. Even in industrialized regions, such as Europe, where conventional therapies are accessible for the majority of patients, there is a growing interest in and usage of phytomedicine. Plant preparations are not only used as alternative treatment, but also combined with conventional drugs. These combinations deserve careful contemplation, as the complex mixtures of bioactive substances in plants show a potential for interactions. Induction of CYP enzymes and pGP by St John's wort may be the most famous example, but there is much more to consider. In this review, we shed light on what is known about the interactions between botanicals and drugs, in order to make practitioners aware of potential drug-related problems. The main focus of the article is the treatment of inflammatory diseases, accompanied by plant preparations used in Europe. Several of the drugs we discuss here, as basal medication in chronic inflammatory diseases (e.g., methotrexate, janus kinase inhibitors), are also used as oral tumor therapeutics.

Background: Previous studies provided the first evidence that the importance of olfaction decreases with the duration of olfactory dysfunction (OD)., Objective: To evaluate differences in olfactory-related quality of life (QoL) between patients with new-onset and persistent smell loss (>4 weeks) during the coronavirus-19 (COVID-19) pandemic and patients with persistent postinfectious OD (PIOD) that were recruited before the pandemic., Methods: This was a retrospective study that included 149 patients with self-reported OD. The olfactory-related QoL was measured using the questionnaire of OD (QOD). The QOD measures the degree to which patients (i) adjust and cope with smell loss (QOD-positive statement [QOD-PS]), (ii) suffer from distorted odor perceptions (QOD-parosmia [QOD-PAR]), and (iii) suffer from smell loss in general (QOD-negative statement [QOD-NS]). Self-perceived chemosensory function, demographics, olfactory function, and duration of smell loss were evaluated. Analyses of variance were used to depict differences in QoL-outcomes between different OD groups., Results: All patients included during the COVID-19 pandemic reported an extensive loss of chemosensory functions of smell, taste, and flavor perception. Psychophysical retronasal screening testing showed olfactory impairments in more than half of these patients. One-way analysis of variance and posthoc tests revealed that the QOD-NS was significantly higher in the new-onset OD group than the PIOD group. At the same time, the QOD-PS score was significantly higher in the PIOD and the persistent COVID-19 OD group than in the new-onset OD group., Conclusion: We showed that patients with persistent OD experienced better olfactory-related adjustment and lower QoL-impairment scores than those with recent-onset smell loss, suggesting that the olfactory-related QoL might change as a function of time after symptom onset.

Recent research shows that the human sense of smell seems to be more efficient than previously believed and to have a major impact on our health condition and quality of life. During the COVID-19 pandemic, an increased clinical interest has become evident for the SARS-CoV-2 related impact on olfactory function. This article highlights important aspects in the diagnosis and therapy of the chemical senses., (© 2021. The Author(s).)

Objectives: Olfactory dysfunction (OD) constitutes a major symptom in Coronavirus Disease 2019 (COVID-19). Yet, most data on smell loss rely on the evaluation of orthonasal olfactory performance. Therefore, we aimed to assess retronasal olfactory function (ROF) over a period of several weeks in proven and suspected COVID-19 patients., Methods: One hundred and one subjects with suspected or laboratory-proven COVID-19 participated in this study. In patients with OD no longer than 4 weeks after initial symptom onset, ROF was measured with the 7-item Candy Smell Test ten times over 7 weeks., Results: Olfactory function was decreased in the investigated patients and remained decreased over the course of 7 weeks. One-way repeated-measures ANOVA revealed no significant difference of ROF between different measurement time points. However, self-assessment of smell and flavour improved significantly (p = 0.013 and p = 0.043), but did not show complete recovery., Conclusion: The current investigation revealed significant improvements in subjective smell and flavour perception over the course of 7 weeks in proven and suspected COVID-19 patients suffering from acute OD. However, objectively measured ROF based on a screening test revealed no improvements within the same time period., (© 2021. The Author(s).)

Background: Sugar overconsumption is a major contributor to overweight and obesity, with daily consumption greatly exceeding the WHO's recommendations. The aim of the present study was to determine whether using a functionally modified sugar shaker as a food environment nudge could be an effective means to reduce the sugar used in hot beverages., Methods: Sugar shakers were functionally modified to reduce the amount of sugar in each pour by 47%. A real-world experiment was conducted to compare the amount of added sugar per hot beverage during default and nudge conditions over the course of four weeks (17,233 hot beverages sold) in a university take-away café. In addition, 59 customers were surveyed to evaluate the acceptance of the intervention., Results: Modifying the functional design of sugar shakers resulted in a reduction of added sugar by 20% (d = 1.35) compared to the default condition. In the survey, most participants evaluated the intervention strategy positively., Conclusion: The present real-world experiment demonstrates that a simple environmental intervention can significantly reduce sugar consumption in public places while meeting with consumer approval, making it a promising means of reducing sugar overconsumption., (© 2021. The Author(s).)

Infectious diseases pose a serious threat to humans. Therefore, it is crucial to understand how accurately people perceive these risks. However, accuracy can be operationalized differently depending on the standard of comparison. The present study investigated accuracy in risk perceptions for three infectious diseases (avian influenza, seasonal influenza, common cold) using three different standards for accuracy: Social comparison (self vs. others' risk perceptions), general problem level (risk perceptions for diseases with varying threat levels), and dynamic problem level (risk perceptions during epidemics/seasons vs. nonepidemic/off-season times). Four online surveys were conducted using a repeated cross-sectional design. Two surveys were conducted during epidemics/seasons of avian influenza, seasonal influenza, and common cold in 2006 (n = 387) and 2016 (n = 370) and two surveys during nonepidemic/off-season times for the three diseases in 2009 (n = 792) during a swine flu outbreak and in 2018 (n = 422) during no outbreak of zoonotic influenza. While on average participants felt less at risk than others, indicating an optimistic bias, risk perceptions matched the magnitude of risk associated with the three infectious diseases. Importantly, a significant three-way interaction indicated dynamic accuracy in risk perceptions: Participants felt more at risk for seasonal influenza and common cold during influenza and cold seasons, compared with off-season times. However, these dynamic increases were more pronounced in the perceived risk for others than for oneself (optimistic bias). The results emphasize the importance of using multiple approaches to assess accuracy of risk perception as they provided different information on how accurately people gauge their risk when facing infectious diseases., (© 2021 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are common forms of idiopathic nephrotic syndrome. The causes of these diseases are incompletely understood, but the response of patients to immunosuppressive therapies suggests that their pathogenesis is at least in part immune mediated. Preclinical and clinical research indicates that activation of the classical pathway of complement contributes to glomerular injury in FSGS. Glomerular IgM deposits are also prominent in some patients, raising the possibility that IgM is a trigger of classical pathway activation. In the present study, we examined the pattern of complement activation in the glomeruli and plasma of patients with nephrotic syndrome. We also tested whether patients with FSGS and MCD have elevated levels of natural IgM reactive with epitopes on glomerular endothelial cells and cardiolipin. We found evidence of classical pathway activation in patients with idiopathic nephrotic syndrome compared with healthy control subjects. We also detected higher levels of self-reactive IgM to both targets. Based on these results, IgM and classical pathway activation may contribute to disease pathogenesis in some patients with FSGS and MCD. NEW & NOTEWORTHY IgM is detected in biopsies from some patients with nephrotic syndrome, although this has been attributed to passive trapping of the protein. We found, however, that IgM colocalizes with complement activation fragments in some glomeruli. We also found that affected patients had higher levels of IgM reactive to glomerular endothelial cell epitopes. Thus, IgM activates the complement system in the glomeruli of some patients with nephrotic syndrome and may contribute to injury.

BackgroundDuring the COVID-19 pandemic, public perceptions and behaviours have had to adapt rapidly to new risk scenarios and radical behavioural restrictions.AimTo identify major drivers of acceptance of protective behaviours during the 4-week transition from virtually no COVID-19 cases to the nationwide lockdown in Germany (3-25 March 2020).MethodsA serial cross-sectional online survey was administered weekly to ca 1,000 unique individuals for four data collection rounds in March 2020 using non-probability quota samples, representative of the German adult population between 18 and 74 years in terms of age × sex and federal state (n = 3,910). Acceptance of restrictions was regressed on sociodemographic variables, time and psychological variables, e.g. trust, risk perceptions, self-efficacy. Extraction of homogenous clusters was based on knowledge and behaviour.ResultsAcceptance of restrictive policies increased with participants' age and employment in the healthcare sector; cognitive and particularly affective risk perceptions were further significant predictors. Acceptance increased over time, as trust in institutions became more relevant and trust in media became less relevant. The cluster analysis further indicated that having a higher education increased the gap between knowledge and behaviour. Trust in institutions was related to conversion of knowledge into action.ConclusionIdentifying relevant principles that increase acceptance will remain crucial to the development of strategies that help adjust behaviour to control the pandemic, possibly for years to come. Based on our findings, we provide operational recommendations for health authorities regarding data collection, health communication and outreach.

Background: Olfactory dysfunction (OD) is common in the general population, affects the quality of life (QoL), and is suspected to cause depression. Long-term outcome data are lacking and there is a need to improve patient counselling regarding prognosis. We aimed to assess subjective long-term recovery rates, the QoL, and mood disturbance in a group of 65 patients, who were affected with OD., Methods: Out of 325 patients treated for OD between 2003 and 2009  at a smell and taste clinic, 65 patients were included for a follow-up after an average of 8.6 years. A total of 28 patients answered questionnaires only and 37 patients were provided with an additional smell identification test. Among others, questionnaires included a short form of the World Health Organization quality of life questionnaire (WHOQOL-BREF) and the Beck's depression inventory., Results: In the long run, subjective improvement was stated in 33.8% of all patients, with the highest rate of 42.3% in patients with postinfectious OD. The subjective rating of olfactory function on a visual analogue scale was significantly higher at study follow-up compared to first clinical contact (median 1.25 vs. 4.5; U = 469.5, p = 0.001), as were mean identification scores (6.0 ± 3.0 vs. 8.0 ± 4.0, t(18) = 2.51, p = 0.021). The QoL in general was considered reduced in 40% of all patients at follow-up. Furthermore, participants exhibited only minor, if any, depressive symptoms., Conclusion: Despite negative effects of OD on certain activities in daily life, such as cooking, detecting spoiled food, or personal hygiene, it seems that the patients included in this study adapted to the OD in the long-term. The current findings should aid clinicians in patient counselling., (© 2020. The Author(s).)

This study aimed to investigate the perceptual similarity between piperine-induced burning sensations and bitter taste using piperine-impregnated taste strips (PTS). This pilot study included 42 healthy participants. PTS of six ascending concentrations (1 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg piperine/dL 96% ethanol) were presented at the anterior tongue, and participants rated perceived intensity and duration. Then, participants performed a spatial discrimination task in which they had to report which of the two strips presented to the anterior tongue contained an irritating stimulus when one strip was always a PTS while the other strip was impregnated with either a single taste quality (sweet or bitter) or a blank strip. Repeated measures one-way ANOVA revealed that burning sensations of higher concentrated PTS were perceived more intense and more prolonged compared to lower concentrated PTS. McNemar's test showed that PTS were identified correctly significantly less often when presented with bitter strips compared to when presented with blank ( p = 0.002) or sweet strips ( p = 0.017). Our results showed that bitter taste disrupts the spatial discrimination of piperine-evoked burning sensations. PTS might serve as a basis for further studies on disease-specific patterns in chemosensory disorders.

Background: Inequalities in health and wealth distributions are becoming pressing societal problems in many countries. How these inequalities are perceived and to what degree perceptions are aligned with actual distributions, is important for trust in public health services, social and economic policies, and policymakers. This study aims to assess perceived and desired levels of inequality in health and wealth in Germany and the UK., Methods: The online-survey was filled out by 769 volunteers (322 from Germany, 447 from the UK), recruited from an existing commercial panel (Prolific Academic) or via Facebook advertisements in 2019. Perceived and ideal national health and wealth distributions were assessed and compared to actual health indicators (i.e. days absent from work, number of visits to general practitioners (GPs) and self-rated health), and actual wealth distributions with t-tests., Results: A pronounced gap emerged between the estimated, ideal and actual inequality. Both samples strikingly underestimated the proportion of (very) good health in the national distribution by a factor of ~ 2.3 (participants estimated that 34% of the German and 36% of the UK population respectively are very healthy or healthy, while the actual proportion in the population was 75% in Germany and 84% in the UK, P < 0.001 for all). Moreover, actual health distributions were much closer to the desired than the perceived health distributions (78% of German and 72% of UK participants ideally being very healthy or healthy). A reversed pattern of results emerged for wealth in both samples, with wealth inequality being strikingly worse than desired and inequality being underestimated by a factor ~ 1.7 (P < 0.001 for all). Results were consistent across demographic groups., Conclusions: Respondents in both Germany and the UK have profoundly negative misperceptions regarding the distribution of health, which contrasts with starkly positive misperceptions regarding the distribution of wealth, indicating that the public is healthier but poorer than they think. More importantly, from a public health perspective, a high level of consensus emerged, with both healthy and wealthy participants misperceiving health and wealth distributions.

Background: The outbreak and global spread of COVID-19 was accompanied by an increase in reports of stigmatization of Chinese and Asian-looking people. The behavioral immune system provides a framework for stigmatization in response to infectious disease threats. Specifically, stigmatization might increase with rising levels of infectious disease threat. The present study aimed to examine this hypothesis during the early phase of the COVID-19 pandemic., Methods: As part of the "EUCLID" project ( https://euclid.dbvis.de ), a total of 5011 persons from Germany were surveyed via an online-questionnaire between February 2 nd and April 3 rd , 2020, covering the progression of the COVID-19 pandemic over three time periods which were defined by critical events., Results: There was no evidence for an increase in the stigmatization of Chinese and Asian-looking people across three topics, that is personal proximity, air travel, and medical measures upon arrival from China., Conclusions: The present findings provide good news in that participants showed an adaptive response to the infectious disease threat rather than displaying increased stigmatization. Further research is necessary to specify the conditions that increase the risk of stigmatization in response to infectious disease threats.

During the next few months or years, vaccination against SARS-CoV-2 infection will significantly reduce the morbidity and mortality of COVID-19. However, additional measures are needed to protect those who are still not immunized. This is even more important in view of new viral mutations that result in increased transmission rates. We propose that the use of long-standing medicinal solutions based on hypochloric acid (HOCl) and intended for application on wounds may be effective as a gargling solution or nasal irrigation in blocking transmission of the virus. Here, we propose the use of HOCl-containing solutions for blocking the transmission of SARS-CoV-2 in combination with other prevention measures. This may constitute another important cornerstone in the fight against the COVID-19 pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Thieme. All rights reserved.)

Background: Since humans are social animals, social relations are incredibly important. However, in cases of contagious diseases such as the flu, social contacts also pose a health risk. According to prominent health behavior change theories, perceiving a risk for one's health motivates precautionary behaviors. The "behavioral immune system" approach suggests that social distancing might be triggered as a precautionary, evolutionarily learned behavior to prevent transmitting contagious diseases through social contact. This study examines the link between personal risk perception for an infectious disease and precautionary behavior for disease-prevention in the context of social relationships., Methods: At 2-week intervals during the first semester, 100 Psychology freshmen indicated their flu risk perception, whether they had been ill during the previous week, and their friendships within their freshmen network for eight time points., Results: Social network analysis revealed that participants who reported a high flu risk perception listed fewer friends ( B = -0.10, OR = 0.91, p = 0.026), and were more likely to be ill at the next measuring point ( B = 0.26, OR = 1.30, p = 0.005). Incoming friendship nominations increased the likelihood of illness ( B = 0.14, OR = 1.15, p = 0.008), while the reduced number of friendship nominations only marginally decreased this likelihood ( B = -0.07, OR = 0.93, p = 0.052)., Conclusion: In accordance with the concept of a "behavioral immune system," participants with high flu risk perception displayed a social precautionary distancing even when in an environment, in which the behavior was ineffective to prevent an illness., Competing Interests: WG has received honoraria for lecturing/consultation from Amgen, Bayer, Biogen, Celgene, Genzyme, Merck Serono, MSD, Mundipharma, Novartis Pharma, Roche, Sanofi, and Teva, as well as research support from Biogen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Giese, Gamp, Stok, Gaissmaier, Schupp and Renner.)

Between 2014 and 2022, the 5 German research networks AEQUIPA, CAPITAL4HEALTH, HLCA, PartKommPlus, and SMARTACT are investigating topics of primary prevention and health promotion with the aim of further deepening the evidence base in these areas. The work of the 5 research networks for primary prevention and health promotion is presented, analysed, and discussed from an internal perspective. A model of evidence-based public health serves as a structuring framework.The 5 research networks use a variety of access routes for the generation of evidence with regard to the participation of nonacademic, civil society actors and users. There is a wide range of study designs - from randomised controlled trials and systematic reviews to diverse qualitative designs. The use of models and theories supports the evidence base. Beyond evidence generation, all research networks focus on at least exemplary implementation of new evidence.Due to the diversity of methods, a diversified evidence-based approach can be realised, taking into account network-specific aspects. Structural circumstances limit the further systematic strengthening of the evidence base. In particular, the involvement of nonacademic, civil society actors for the work with hard-to-reach target groups often cannot be financed or is considered too time consuming under the given circumstances. The COVID-19 pandemic highlights the importance of a flexible spectrum of methods, employing both digital and analogue methods in a meaningful way.

Cardiovascular disease (CVD) is the most common cause of death in patients with native and post-transplant chronic kidney disease (CKD). To identify new biomarkers of vascular injury and inflammation, we analyzed the proteome of plasma and circulating extracellular vesicles (EVs) in native and post-transplant CKD patients utilizing an aptamer-based assay. Proteins of angiogenesis were significantly higher in native and post-transplant CKD patients versus healthy controls. Ingenuity pathway analysis (IPA) indicated Ephrin receptor signaling, serine biosynthesis, and transforming growth factor-β as the top pathways activated in both CKD groups. Pro-inflammatory proteins were significantly higher only in the EVs of native CKD patients. IPA indicated acute phase response signaling, insulin-like growth factor-1, tumor necrosis factor-α, and interleukin-6 pathway activation. These data indicate that pathways of angiogenesis and inflammation are activated in CKD patients' plasma and EVs, respectively. The pathways common in both native and post-transplant CKD may signal similar mechanisms of CVD.

Introduction: How do people receive unexpected positive health risk information? While common motivational accounts predict acceptance, consistency accounts such as the cue-adaptive reasoning account (CARA) predict a 'lack of reassurance'., Objectives: We therefore tested (1) whether people prefer striving for positivity or retaining a sense of self-consistency ('lack of reassurance'), and (2) if there are systematic differences in short- and long-term reception, which would indicate temporal dynamics in processing., Methods: As part of a longitudinal cohort study, participants of a community health screening ( N  = 1,055) received their actual cholesterol readings. Feedback reception was assessed immediately, at one month and six months., Results: Processing trajectories for unexpected positive feedback showed a significant 'lack of reassurance' effect over time compared with expected positive feedback, while unexpected negative feedback was less threatening than expected negative feedback., Conclusions: The perseverance of this 'lack of reassurance' over time indicates that striving for consistency in self-views is a robust phenomenon, even if it means forfeiting a better view of one's own health., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

To contain the spread of Covid-19, engagement in protective behaviors across the population is of great importance. The present study investigated protective behavior intentions during the early phases of Covid-19 in Germany (February 2-April 3, 2020) as a function of threat level and age using data from 4,940 participants in the EUCLID project. Results indicated that the intention to engage in social distancing increased sharply with threat level. Intentions for personal hygiene also increased, although to a lesser extent. While age only had a small overall effect on behavioral intentions, differential patterns emerged. After the lockdown was introduced, the impact of age decreased for social distancing and hygiene behavior intentions but increased for seeing a doctor. Since containing the Covid-19 pandemic depends on high adoption rates of protective behaviors, future research should track sustained phases of the pandemic, including the easing of restrictions and possible new waves of infections.

Background: Nutrition apps are effective in changing eating behavior and diet-related health risk factors. However, while they may curb growing overweight and obesity rates, widespread adoption is yet to be achieved. Hence, profound knowledge regarding factors motivating and hindering (long-term) nutrition app use is crucial for developing design guidelines aimed at supporting uptake and prolonged use of nutrition apps., Objective: In this systematic review, we synthesized the literature on barriers to and facilitators for nutrition app use across disciplines including empirical qualitative and quantitative studies with current users, ex-users, and nonusers of nutrition apps., Methods: A systematic literature search including 6 databases (PubMed, Web of Science, PsychINFO, PSYNDEX, PsycArticles, and SPORTDiscus) as well as backward and forward citation search was conducted. Search strategy, inclusion and exclusion criteria, and the planned data extraction process were preregistered. All empirical qualitative and quantitative studies published in German or English were eligible for inclusion if they examined adolescents (aged 13-18) or adults who were either current users, ex-users, and nonusers of nutrition apps. Based on qualitative content analysis, extracted individual barriers and facilitators were grouped into categories., Results: A total of 28 publications were identified as eligible. A framework with a 3-level hierarchy was designed which grouped 328 individual barriers and facilitators into 23 subcategories, 12 categories, and 4 clusters that focus on either the individual user (goal setting and goal striving, motivation, routines, lack of awareness of knowledge), different aspects of the app and the smartphone (features, usability of the app or food database, technical issues, data security, accuracy/trustworthiness, costs), positive and negative outcomes of nutrition app use, or interactions between the user and their social environment., Conclusions: The resulting conceptual framework underlines a pronounced diversity of reasons for (not) using nutrition apps, indicating that there is no "one-size-fits-all" approach for uptake and prolonged use of nutrition apps. Hence, tailoring nutrition apps to needs of specific user groups seems promising for increasing engagement.

Research shows that retrospective memory is often more extreme than in-the-moment experiences. While investigations into this phenomenon have mostly focused on distinct, one-time experiences, we examined it with respect to recurring day-to-day experiences in the eating domain, focusing on variables of the snapshot model-i.e., the most intense and the final experience. We used a smartphone-based Ecological Momentary Assessment to assess the food intake and eating happiness of 103 participants (82.52% female, Mage = 21.97 years) over eight days, and then calculated their best (positive peak), worst (negative peak) and final experiences. Remembered eating happiness was assessed immediately after the study (immediate recall) and after four weeks (delayed recall). A significant memory-experience gap was revealed at immediate recall (d = .53). Remembered eating happiness was predicted by the worst eating experience (β = .41, p < .001), but not by the best or final eating experience. Analyzing changes over time did not show a significant memory-experience gap at delayed recall, but did reveal a similar influence of the worst eating experience (β = .39, p < .001). Findings indicate that, in the domain of eating, retrospective memory is mainly influenced by negative experiences. Overall, the results indicate that the snapshot model is a valid conceptualization to explain recall of both outstanding and day-to-day experiences., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.