Search

Funder: Program of Introducing Talents of Discipline to Universities, Plan 111 (No. B18015). National Key R&D Program of China (No. 2018YFC1312900)., Emerging evidence shows that the coronavirus disease 2019 (COVID-19) pandemic is negatively affecting mental health around the globe. Interventions to alleviate the psychological impact of the pandemic are urgently needed. Whether mindfulness practice may protect against the harmful emotional effects of a pandemic crisis remains hitherto unknown. We investigated the influence of mindfulness training on mental health during the COVID-19 outbreak in China. We hypothesized that mindfulness practitioners might manifest less pandemic-related distress, depression, anxiety, and stress than non-practitioners and that more frequent practice would be associated with an improvement in mental health during the pandemic. Therefore, we assessed pandemic-related distress and symptoms of depression, anxiety, and stress, as well as the frequency of meditation practice at the peak of new infections (Feb 4–5; N = 673) and three weeks later (Feb 29–30; N = 521) in mindfulness practitioners via online questionnaires. Self-reported symptoms were also collected from non-practitioners at peak time only (N = 1550). We found lower scores of pandemic-related distress in mindfulness practitioners compared to non-practitioners. In general, older participants showed fewer symptoms of depression and anxiety. In younger practitioners, pandemic-related distress decreased from peak to follow-up. Importantly, increased mindfulness training during the preceding two weeks was associated with lower scores of depression and anxiety at both assessments. Likewise, practice frequency predicted individual improvement in scores of depression, anxiety, and stress at follow-up. Our results indicate that mindfulness meditation might be a viable low-cost intervention to mitigate the psychological impact of the COVID-19 crisis and future pandemics.

Social animals invest time and resources into building and adapting their social environment, which emerges not only from their own but also from the decisions of other group members. Thus, individuals have to monitor interactions between others and potentially decide when and how to interfere to prevent damage to their own investment. These interventions can be subtle, as in the case of affiliative interactions such as grooming, but they can inform us about how animals structure their world and influence other group members. Here, we used interventions into grooming bouts in 29 female rhesus macaques (Macaca mulatta) to determine who intervened into which grooming bouts, why, and what determined intervention outcomes, based on kinship, dominance rank, and affiliative relationships between groomers and (potential) interveners. Using 1132 grooming bouts and 521 interventions, we show that high dominance rank of groomers reduced the risk of intervention. Bystanders, particularly when high-ranking, intervened in grooming of their kin, close affiliates, and close-ranked competitors. Interveners gained access to their close affiliates for subsequent grooming. Affiliative relationship and rank determined intervention outcomes, with reduced aggression risk facilitating grooming involving three individuals. Thus, interventions in this species involved the monitoring of grooming interactions, decision-making based on several individual and dyadic characteristics, and potentially allowed individuals to broaden their access to grooming partners, protect their own relationships, and influence their social niche.

PURPOSE To evaluate the feasibility and effectiveness of computed tomography (CT)-guided percutaneous drainage (PD) in patients with iatrogenic pneumoperitoneum presenting as acute abdomen. MATERIALS AND METHODS In this retrospective, single-center cohort study, 16 consecutive patients (9 males, 7 females; median age, 67.5 [51-85] years) undergoing PD for managing acute abdomen caused by iatrogenic pneumoperitoneum between 2013 and 2019 were analyzed. Inclusion criteria were clinical signs of acute abdomen that was unresponsive to conservative management and pneumoperitoneum due to an iatrogenic cause after PD, observed using CT imaging. Volumetry of pneumoperitoneum was performed using computer-aided image segmentation. To evaluate the clinical outcome, the paired t-test was performed to analyze the course of pain intensity on the numerical pain rating scale (NPRS, 0-10). Patient records were reviewed to determine PD-related adverse events and median drain duration. RESULTS The median pneumoperitoneum volume was 891.1 (127.7-3,677.0) mL. All PD procedures were successfully performed, with symptom relief and immediate abdominal decompression (mean segmental volume reduction, 79.8% ± 13.5). Acute abdomen symptoms were resolved, with significant improvement in pain intensity between the day of the PD procedure and the first day after the procdure (mean NPRS scores, 3.3 ± 1.9 vs 0.8 ± 1.0; P < .001). The median drain duration was 2 (1-3) days. No PD-associated adverse events were observed. After PD, 14 patients required only conservative management, whereas 2 patients with anastomotic leakage required additional surgery as they showed signs of persisting sepsis and generalized peritonitis. CONCLUSIONS PD is a safe and suitable procedure for the management of symptoms in patients with iatrogenic pneumoperitoneum presenting as acute abdomen.

Background In the emergency setting of acute ischemic stroke, seizures have been reported in up to 4% of patients. In the absence of arterial occlusion, seizures may also cause abnormalities in CT perfusion in 78% of cases when the time window from onset to imaging is short. Both hyperperfusion and hypoperfusion in the postictal state have been described. Also, though rarely reported, postictal perfusion changes can be uni-hemispheric. In these cases, perfusion maps should be analyzed thoroughly, since perfusion reconstruction software relies heavily on a “normal” contralateral perfusion status. Case presentation A 39-year-old man was found on the ground with a minor head injury. On admission, his reactions were generally slow, but there were no other neurological symptoms, and blood pressure was low. The patient had a history of primary generalized epilepsy and admitted to dropping off his anti-epileptic medication. He was transferred to the radiological department for imaging but shortly before began to experience generalized onset tonic-clonic seizures which were brought under control by intravenous therapy with 10 mg diazepam. After approximately 15 min, a multimodal CT scan was performed, revealing marked changes in the perfusion of the brain hemispheres and posterior fossa, with sharp delimitation at the midline. Blood gas analysis was congruent with respiratory acidosis. Clinically, the patient remained awake without developing any new symptoms. He gradually recovered over the following 3 h and, against our medical recommendation, discharged himself from the hospital. Conclusions To the authors’ knowledge, this is the first report of an early postictal state describing sharply delimited uni-hemispheric hyperperfusion and hemispheric alteration of the cerebellum with an equally split rhombencephalon. Surprisingly, these changes were not associated with any focal neurological signs. To prevent misdiagnosis of perfusion alterations in seizures, radiologists and neurologists should be aware of the limitations of CT perfusion maps and software reconstructions. Novel use of CT perfusion reconstruction using peak enhancement helped in identifying the cerebral pathology.

Background Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating adult patients with major depressive disorder (MDD) and identified the factors influencing treatment outcome measures (i.e. depression score, dropout, response, and remission rates). Methods The systematic review was performed in PubMed/Medline, EMBASE, PsycINFO, Web of Sciences, and OpenGrey. Two authors performed independent literature screening and data extraction. The primary outcomes were the standardized mean difference (SMD) for continuous depression scores after treatment and odds ratio (OR) dropout rate; secondary outcomes included ORs for response and remission rates. Random effects models with 95% confidence intervals were employed in all outcomes. The overall effect of tDCS was investigated by meta-analysis. Sources of heterogeneity were explored via subgroup analyses, meta-regression, sensitivity analyses, and assessment of publication bias. Results Twelve randomised, sham-controlled trials (active group: N = 251, sham group: N = 204) were included. Overall, the integrated depression score of the active group after treatment was significantly lower than that of the sham group (g = − 0.442, p = 0.017), and further analysis showed that only tDCS + medication achieved a significant lower score (g = − 0.855, p p = 0.006), while the response rate remained unchanged for the other three therapies. Dropout and remission rates were similar in the active and sham groups for each therapy and also for the overall intervention. The meta-regression results showed that current intensity is the only predictor for the response rate. None of publication bias was identified. Conclusion The effect size of tDCS treatment was obviously larger in depression score compared with sham stimulation. The tDCS combined selective serotonin re-uptake inhibitors is the optimized therapy that is effective on depression score and response rate. tDCS monotherapy and combined psychotherapy have no significant effects. The most important parameter for optimization in future trials is treatment strategy.

Over the last decades, the frequency of allergic disorders has steadily increased. Immunologically, allergies are caused by abnormal immune responses directed against otherwise harmless antigens derived from our environment. Two of the main cell types driving allergic sensitization and inflammation are IgE-producing plasma cells and Th2 cells. The acute activation of T and B cells, their differentiation into effector cells, as well as the formation of immunological memory are paralleled by distinct changes in cellular metabolism. Understanding the functional consequences of these metabolic changes is the focus of a new research field termed “immune metabolism”. Currently, the contribution of metabolic changes in T and B cells to either the development or maintenance of allergies is not completely understood. Therefore, this mini review will introduce the fundamentals of energy metabolism, its connection to immune metabolism, and subsequently focus on the metabolic phenotypes of IL-4-activated B cells and Th2 cells.

Significance Vaccines profit from the addition of adjuvants to better and more specifically initiate, amplify, and shape immune responses. Although the number of adjuvant candidates has steadily increased, peaking in the current SARS-CoV-2 pandemic, little is known about their inherent mode of action. Using human blood immune cells, we established a multilayer method to systematically assess the adjuvants’ effects on innate and adaptive immune cells. By employing a multiplex analysis with cells from 30 different donors, we determined important patterns of adjuvant function. Moreover, we demonstrate correlates of an antiviral immune response using a Toll-like receptor 7/8 ligand adjuvant and single-stranded RNA. This knowledge about adjuvants’ distinct immune signatures supports the selection of safe and effective adjuvants for future vaccines., The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast to commonly used adjuvants, such as aluminum hydroxide, Toll-like receptor (TLR) agonists induced robust phenotypic and functional DC maturation. In a DC-lymphocyte coculture system, we investigated the ensuing immune reactions. While monophosphoryl lipid A synthetic, a TLR4 ligand, induced checkpoint inhibitors indicative for immune exhaustion, the TLR7/8 agonist Resiquimod (R848) induced prominent type-1 interferon and interleukin 6 responses and robust CTL, B-cell, and NK-cell proliferation, which is particularly suited for antiviral immune responses. The recently licensed COVID-19 vaccines, BNT162b and mRNA-1273, are both based on single-stranded RNA. Indeed, we could confirm that the cytokine profile induced by lipid-complexed RNA was almost identical to the pattern induced by R848. Although this awaits further investigation, our results suggest that their efficacy involves the highly efficient antiviral response pattern stimulated by the RNAs’ TLR7/8 activation.

The assessment of mucosal immunity as a component of animal health is an important aspect for the understanding of variation in host immunity, and its tradeoff against other life-history traits. We investigated immunoglobulin A (IgA), the major type of antibody associated with mucosal immunity, in relation to changes in parasitic burden following anthelminthic treatment in noninvasively collected fecal samples in a semi-free ranging group of Barbary macaques (Macaca sylvanus). We measured IgA in 340 fecal samples of fourteen females and nine males. As IgA has been found to be responsive to stressors, we also related fecal IgA (fIgA) levels to fecal glucocorticoid metabolites (fGCM) measured in the same samples as part of a previous study. We found a high variability within and between individual fIgA levels over time. Running generalized additive mixed models, we found that fIgA levels were higher in males than in females, but did not change in response to the anthelmintic treatment and the resulting reduction in worm burden. Instead, fIgA level changes were significantly correlated to changes in fGCM levels. Our findings indicate that due to the strong responsiveness of fIgA to HPA-axis activity, the measurement of fIgA may have certain limitations with respect to reflecting gastrointestinal parasitic burden. Moreover, the responsiveness of fIgA to stressors interferes with the interpretation of IgA levels in fecal samples as a measure of mucosal immunity, at least in our study population of the Barbary macaques.

Abstract The source of maternal energy supporting reproduction (i.e., stored or incoming) is an important factor determining different breeding strategies (capital, income or mixed) in female mammals. Key periods of energy storage and allocation might induce behavioral and physiological shifts in females, and investigating their distribution throughout reproduction helps in determining vulnerable phases shaping female reproductive success. Here, we examined the effects of reproductive state on activity budget, feeding behavior, and urinary C-peptide (uCP) levels, a physiological marker of energy balance, in 43 wild female Assamese macaques (Macaca assamensis). Over a 13-month study period, we collected 96,266 instantaneous records of activity and 905 urine samples. We found that early lactating females and non-gestating–non-lactating females follow an energy-saving strategy consisting of resting more at the expense of feeding and consuming mostly fruits which contributed to enhancing their energy intake and feeding efficiency. We found an opposite pattern in gestating and late lactating females who feed more at the expense of resting and consume mostly seeds, providing a fiber-rich diet. Storing food into cheek pouches increased throughout gestation while it decreased all along with lactation. Lastly, we found the highest uCP levels during late gestation. Our results reflect different feeding adaptations in response to the energetic costs of reproduction and suggest a critical role of fat accumulation before conception and metabolizing fat during gestation and lactation. Overall, our study provides an integrative picture of the energetics of reproduction in a seasonal species and contributes to our understanding of the diversity of behavioral and physiological adaptations shaping female reproductive success. Significance statement To offset their substantial energetic investment in reproduction, mammalian females may modify their behavior and the way they extract energy from their environment. In addition, as a result of heightened energy expenditure, female reproduction might trigger physiological shifts. To date, most studies investigated the energetic costs of female reproduction using either a behavioral or a physiological approach. To arrive at a more comprehensive picture, we combined behavioral data with a physiological marker of energy balance, i.e., urinary C-peptide, in a seasonal primate species in its natural habitat. Our results indicate that throughout the reproductive cycle, behavioral and physiological adaptations operate concomitantly, inducing modifications in female activity budget, feeding behavior, and suggesting shifts in fat use. Overall, our results illustrate the relevance of combining data on behavior and hormones to investigate breeding strategies in coping with the energetic costs of reproduction.

Purpose of Review The incidence of allergies is increasing and has been associated with several environmental factors including westernized diets. Changes in environment and nutrition can result in dysbiosis of the skin, gut, and lung microbiota altering the production of microbial metabolites, which may in turn generate epigenetic modifications. The present review addresses studies on pectin-mediated effects on allergies, including the immune modulating mechanisms by bacterial metabolites. Recent Findings Recently, microbiota have gained attention as target for allergy intervention, especially with prebiotics, that are able to stimulate the growth and activity of certain microorganisms. Dietary fibers, which cannot be digested in the gastrointestinal tract, can alter the gut microbiota and lead to increased local and systemic concentrations of gut microbiota-derived short chain fatty acids (SCFAs). These can promote the generation of peripheral regulatory T cells (Treg) by epigenetic modulation and suppress the inflammatory function of dendritic cells (DCs) by transcriptional modulation. The dietary fiber pectin (a plant-derived polysaccharide commonly used as gelling agent and dietary supplement) can alter the ratio of Firmicutes to Bacteroidetes in gut and lung microbiota, increasing the concentrations of SCFAs in feces and sera, and reducing the development of airway inflammation by suppressing DC function. Summary Pectin has shown immunomodulatory effects on allergies, although the underlying mechanisms still need to be elucidated. It has been suggested that the different types of pectin may exert direct and/or indirect immunomodulatory effects through different mechanisms. However, little is known about the relation of certain pectin structures to allergies.

Infant care from adult males is unexpected in species with high paternity uncertainty. Still, males of several polygynandrous primates engage in frequent affiliative interactions with infants. Two non‐exclusive hypotheses link male infant care to male mating strategies. The paternal investment hypothesis views infant care as a male strategy to maximize the survival of sired offspring, while the mating effort hypothesis predicts that females reward males who cared for their infant by preferably mating with them. Both hypotheses predict a positive relationship between infant care and matings with a particular female. However, the paternal investment hypothesis predicts that increased matings come before infant care whereas the mating effort hypothesis predicts that infant care precedes an increase in matings. Both hypotheses are usually tested from the perspective of the proportion of matings and care that individual females engage in and receive, rather than from the perspective of the care and mating behaviour of individual males. We tested the relationships between care and mating from both female and male perspectives in Barbary macaques. Mating predicted subsequent care and care predicted subsequent mating when viewed from the male but not the female perspective. Males mainly cared for infants of their main mating partners, but infants were not mainly cared for by their likely father. Males mated more with the mothers of their favourite infants, but females did not mate more with the main caretakers of their infants. We suggest that females do not choose their mating partners based on previous infant care, increasing paternity confusion. Males might try to increase paternal investment by distributing the care according to their own instead of female mating history. Further, males pursue females for mating opportunities based on previous care.

While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT) with allergen extracts is the only available curative treatment option. However, the risk of anaphylactic reactions, long treatment duration, varying extract quality, and underrepresentation of certain allergens currently prevent many patients from successfully undergoing SIT. Novel strategies are needed to enhance efficacy, safety, and convenience of allergy treatment. Fusion proteins combining allergen and adjuvant into a single molecule can efficiently induce immune responses by targeting the allergen to the relevant immune cells in vivo. Simultaneous co-delivery of both antigen and adjuvant to the same cell in a fixed molecular ratio triggers the uptake and presentation of the conjugated allergen in the context of the adjuvant-induced immune cell activation. This review summarizes the published strategies to improve the treatment of type I allergies using fusion proteins consisting of allergen (peptides) and either (1) immune-activating bacterial (flagellin, MPLA, S-layer, cholera-, and tetanus toxin), (2) viral (PreS, VP-1, TAT), or (3) fungal (FIP-fve) components, (4) immune-activating DNA motifs, (5) forced delivery of allergens to the MHC-II loading pathway, and (6) killing of immune cells expressing allergen-specific IgE by fusion of the allergen to diphtheria toxin.

As underlying heart diseases of right ventricular tachyarrhythmias, ARVC causes wall-motion abnormalities based on fibrofatty myocardial degeneration, while RVOT-VT and BrS are thought to lack phenotypic MR characteristics. To examine whether cardiac magnetic resonance (CMR) feature tracking (FT) in addition to ARVC objectively facilitates detection of myocardial functional impairments in RVOT-VT and BrS. Cine MR datasets of four retrospectively enrolled, age-matched study groups [n = 65; 16 ARVC, 26 RVOT-VT, 9 BrS, 14 healthy volunteers (HV)] were independently assessed by two distinctly experienced investigators regarding myocardial function using CMR-FT. Global strain (%) and strainrate (s−1) in radial and longitudinal orientation were assessed at RVOT as well as for left (LV) and right (RV) ventricle at a basal, medial and apical section with the addition of a biventricular circumferential orientation. RV longitudinal and radial basal strain (%) in ARVC (− 12.9 ± 4.2; 11.4 ± 5.1) were significantly impaired compared to RVOT-VT (− 18.0 ± 2.5, p ≤ 0.005; 16.4 ± 5.2, p ≤ 0.05). Synergistically, RVOT endocardial radial strain (%) in ARVC (33.8 ± 22.7) was significantly lower (p ≤ 0.05) than in RVOT-VT (54.3 ± 14.5). For differentiation against BrS, RV basal and medial radial strain values (%) (13.3 ± 6.1; 11.8 ± 2.9) were significantly reduced when compared to HV (21.0 ± 6.9, p ≤ 0.05; 20.1 ± 6.6, p ≤ 0.005), even in case of a normal RV ejection fraction (EF) (> 45%; n = 6) (12.0 ± 2.7 vs. 20.1 ± 6.6, p ≤ 0.05). CMR-FT facilitates relevant differentiation in patients with right ventricular tachyarrhythmias: between ARVC against RVOT-VT and HV as well as between BrS with even a preserved EF against HV.

Higher rates of missed pathologies, caused by a lack of professional experience or systematic search, suggest that a methodical approach to radiological analysis can be learned. Thus, the aim of this study is to investigate the efficiency of different principles of screening stroke CTs for cerebrovascular diseases between radiologists and neuroradiologists with different levels of experience in relation to professional experience. A set of anonymous CT images of 20 patients, with a suspected stroke, was individually presented to 12 radiologists with different levels of professional experience. Meanwhile, their fixation position was recorded by an eye-tracking system. For statistical analysis, the interobserver variability and accuracy of lesion detection were evaluated, taking the individual level of professional experience into account. The sensitivity of the observer depends on the professional experience, also determined by a systematic observation sequence and knowledge of the course of the disease. The duration of eye fixation with inexperienced assessors was significantly longer for conspicuous findings, while experienced assessors were more likely to fix clinically relevant regions. The retention time of ocular fixation in important pathological findings did not differ significantly between those groups. Our results indicate that experienced radiologists are reducing the number of missed findings through a systematic approach and targeted inspection of important regions. Through raising the awareness of analyzing CT images in systematic patterns, physicians at all levels of experience seem to be able to improve their performance. · Experienced radiologists improve detection rates through targeted inspection of clinically important regions.. · Experienced radiologists reduce time spent on analysis through focused visual attention.. · All levels of experience improve their performance by analyzing CT images systematically..· Kammerer S, Schülke C, Leclaire MD et al. Impact of Working Experience on Image Perception and Image Evaluation Approaches in Stroke Imaging: Results of an Eye-Tracking Study. Fortschr Röntgenstr 2019; 191: 836 - 844. Höhere Raten von verpassten Pathologien, verursacht durch mangelnde Berufserfahrung oder systematische Suche, legen nahe, dass ein methodischer Ansatz zur radiologischen Analyse erlernt werden kann. Ziel dieser Studie ist es daher, die Effizienz verschiedener Prinzipien des Screenings von Schlaganfall-CTs auf zerebrovaskuläre Erkrankungen zwischen Radiologen und Neuroradiologen mit unterschiedlichen Erfahrungsniveaus in Bezug auf die Berufserfahrung zu untersuchen. Anonymisierte CT-Bilder von 20 Patienten mit Verdacht auf einen Schlaganfall wurden 12 Radiologen mit unterschiedlicher Berufserfahrung individuell präsentiert. Währenddessen wurde ihre Fixationsposition durch ein Eye-Tracking-System erfasst. Für die statistische Analyse wurden die Interobserver-Variabilität und die Genauigkeit der Läsionserkennung unter Berücksichtigung der individuellen Berufserfahrung bewertet. Die Sensibilität des Betrachters hängt von seiner beruflichen Erfahrung ab, die auch durch eine systematische Beobachtungsreihenfolge und die Kenntnis des Krankheitsverlaufs bestimmt wird. Die Dauer der Augenfixation von unerfahrenen Bildbefundern war bei auffälligen Befunden deutlich länger, während erfahrene Radiologen eher klinisch relevante Regionen fixierten. Die Verweildauer der okulären Fixation bei wichtigen pathologischen Befunden unterschied sich nicht signifikant zwischen diesen Erfahrungsgruppen. Unsere Ergebnisse zeigen, dass erfahrene Radiologen die Zahl der verpassten Befunde durch einen systematischen Ansatz und eine gezielte Untersuchung wichtiger Regionen reduzieren. Durch die Sensibilisierung für die Analyse von CT-Bildern in systematischen Mustern scheinen Ärzte aller Erfahrungsstufen in der Lage zu sein, ihre Leistung zu verbessern. · Erfahrene Radiologen verbessern die Erkennungsraten durch gezielte Inspektion klinisch wichtiger Regionen.. · Erfahrene Radiologen reduzieren den Zeitaufwand für die Analyse durch gezielte visuelle Aufmerksamkeit.. · Alle Erfahrungsstufen verbessern ihre Leistung durch die systematische Analyse von CT-Bildern..

Treatment of advanced stage anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) with ALK tyrosine kinase inhibitors (TKIs) has been shown to be superior to standard platinum-based chemotherapy. However, secondary progress of disease frequently occurs under ALK inhibitor treatment. The clinical impact of re-biopsies for treatment decisions beyond secondary progress is, however, still under debate. Here, we report on two novel subsequent polyclonal on-and off-target resistance mutations in a patient with ALK-fused NSCLC under ALK inhibitor treatment. A 63-year-old male patient with an advanced stage EML4-ALK fused pulmonary adenocarcinoma was initially successfully treated with the second-generation ALK inhibitor alectinib and upon progressions subsequently with brigatinib, lorlatinib and chemoimmunotherapy (CIT). Progress to alectinib was associated with a so far undescribed ALK mutation (p.A1200_G1201delinsW) which was, however, tractable by brigatinib. An off-target KRAS-mutation (p.Q61K) occurred in association with subsequent progression under second-line TKI treatment. Third-line lorlatinib showed limited efficacy but chemoimmunotherapy resulted in disappearance of the KRAS mutant clone and clinical tumor control for another eight months. In conclusion, we suggest molecular profiling of progressive tumor disease also for ALK-positive NSCLC to personalize treatment in a subgroup of ALK-positive patients. CA extern

Type I allergies are pathological, type 2 inflammatory immune responses against otherwise harmless environmental allergens that arise from complex interactions between different types of immune cells. Activated immune cells undergo extensive changes in phenotype and function to fulfill their effector functions. Hereby, activation, differentiation, proliferation, migration, and mounting of effector responses require metabolic reprogramming. While the metabolic changes associated with activation of dendritic cells, macrophages, and T cells are extensively studied, data about the metabolic phenotypes of the other cell types critically involved in allergic responses (epithelial cells, eosinophils, basophils, mast cells, and ILC2s) are rather limited. This review briefly covers the basics of cellular energy metabolism and its connection to immune cell function. In addition, it summarizes the current state of knowledge in terms of dendritic cell and macrophage metabolism and subsequently focuses on the metabolic changes associated with activation of epithelial cells, eosinophils, basophils, mast cells, as well as ILC2s in allergy. Interestingly, the innate key cell types in allergic inflammation were reported to change their metabolic phenotype during activation, shifting to either glycolysis (epithelial cells, M1 macrophages, DCs, eosinophils, basophils, acutely activated mast cells), oxidative phosphorylation (M2 macrophages, longer term activated mast cells), or fatty acid oxidation (ILC2s). Therefore, immune metabolism is of relevance in allergic diseases and its connection to immune cell effector function needs to be considered to better understand induction and maintenance of allergic responses. Further progress in this field will likely improve both our understanding of disease pathology and enable new treatment targets/strategies.

Allergen immunotherapy (AIT) is the only disease-modifying treatment option for patients with type 1–mediated allergic diseases such as allergic rhinitis/rhinoconjunctivitis with/without allergic asthma. Although many innovations have been developed since the first clinical report of Noon et al in 1911, the improvement of clinical efficacy and tolerability of this treatment is still an important unmet need. Hence, much progress has been made in the characterization of the cell types, cytokines, and intracellular signaling events involved in the development, maintenance, and regulation of allergic reactions, and also in the understanding of the mechanisms of tolerance induction in AIT. This comprehensive review aims to summarize the current innovative approaches in AIT, but also gives an outlook on promising candidates of the future. On the basis of an extensive literature review, integrating a clinical point of view, this article focuses on recent and future innovations regarding biologicals, allergen-derived peptides, recombinant allergens, “Toll”-like receptor agonists and other adjuvants, and novel application routes being developed for future AIT.

Background. Alpha-1 antitrypsin deficiency (AATD) is of importance in the pathogenesis of pulmonary emphysema, chronic obstructive pulmonary diseases (COPD), and bronchiectasis. Various pulmonary disorders are a typical feature of primary immunodeficiency disease (PID). This includes recurrent pulmonary infections, immunodysregulation, and autoinflammatory diseases. As a result, incidence of acute and chronic pulmonary diseases is higher. Interestingly, pulmonary morbidity in PID and AATD share similar features. To study the coexistence of AATD in patients suffering from PID, we performed the underlying investigation. Methods. We evaluated a study group of 149 patients (n = 149) with PID. In total, serum AAT concentrations were available for 110 patients (n = 110). For the identified patients, we analyzed both clinical associations and interactions. Results. Among the investigated patients, reduced serum AAT levels were detected in 7 patients. With regard to the genotype, PI∗ZZ was found in 2 patients, whereas PI∗MZ was observed in 5 patients. Independent of the underlying phenotype, obstructive lung diseases were found in 2 patients with PI∗ZZ and 2 patients with PI∗MZ. Conclusions. In Germany, the estimated percentage for PI∗ZZ and PI∗MZ is 0.01% and 1.9%, respectively. As demonstrated, the ratio in our study group was even higher. We identified seven patients with AATD. Since AATD contributes to pulmonary morbidity in PID patients, systematic underdiagnosis of the coexistence might yield a strong clinical impact. Hence, AAT analysis should be offered to all patients with confirmed PID diagnoses. To strengthen this finding, we suggest the investigation of larger databases.

Patients with schizophrenia spectrum disorder often demonstrate impairments in action-outcome monitoring. Passivity phenomena and hallucinations, in particular, have been related to impairments of efference copy-based predictions which are relevant for the monitoring of outcomes produced by voluntary action. Frontal transcranial direct current stimulation has been shown to improve action-outcome monitoring in healthy subjects. However, whether transcranial direct current stimulation can improve action monitoring in patients with schizophrenia spectrum disorder remains unknown. We investigated whether transcranial direct current stimulation can improve the detection of temporal action-outcome discrepancies in patients with schizophrenia spectrum disorder. On 4 separate days, we applied sham or left cathodal/right anodal transcranial direct current stimulation in a randomized order to frontal (F3/F4), parietal (CP3/CP4) and frontoparietal (F3/CP4) areas of 19 patients with schizophrenia spectrum disorder and 26 healthy control subjects. Action-outcome monitoring was assessed subsequent to 10 min of sham/transcranial direct current stimulation (1.5 mA). After a self-generated (active) or externally generated (passive) key press, subjects were presented with a visual outcome (a dot on the screen), which was presented after various delays (0–417 ms). Participants had to detect delays between the key press and the visual consequence. Symptom subgroups were explored based on the presence or absence of symptoms related to a paranoid-hallucinatory syndrome. In general, delay-detection performance was impaired in the schizophrenia spectrum disorder compared to the healthy control group. Interaction analyses showed group-specific (schizophrenia spectrum disorder versus healthy control group) and symptom-specific (with/without relevant paranoid-hallucinatory symptoms) transcranial direct current stimulation effects. Post hoc tests revealed that frontal transcranial direct current stimulation improved the detection of long delays in active conditions and reduced the proportion of false alarms in undelayed trials of the passive condition in patients. The patients with no or few paranoid-hallucinatory symptoms benefited especially from frontal transcranial direct current stimulation in active conditions, while improvement in the patients with paranoid-hallucinatory symptoms was predominantly reflected in reduced false alarm rates in passive conditions. These data provide some first evidence for the potential utility of transcranial direct current stimulation in improving efference copy mechanisms and action-outcome monitoring in schizophrenia spectrum disorder. Current data indicate that improving efference copy-related processes can be especially effective in patients with no or few positive symptoms, while intersensory matching (i.e. task-relevant in passive conditions) could be more susceptible to improvement in patients with paranoid-hallucinatory symptoms., Straube et al. found that transcranial direct current stimulation of the frontal cortex can improve the detection of delays between actions and their outcomes in patients with schizophrenia spectrum disorder, possibly by affecting efference copy mechanisms in premotor cortices and the supplementary motor area., Graphical Abstract Graphical Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

Background Patients with schizophrenia spectrum disorders (SSD) have severe deficits in speech and gesture processing that contribute considerably to the burden of this disorder. Brain imaging shows left inferior frontal gyrus involvement for impaired processing of co-verbal gestures in patients with schizophrenia. Recently, transcranial direct current stimulation (tDCS) of the left frontal lobe has been shown to modulate processing of co-verbal gestures in healthy subjects. Although tDCS has been used to reduce symptoms of patients with SSD, the effects of tDCS on gesture processing deficits remain hitherto unexplored. Objective Here we tested the hypothesis that inhibitory cathodal tDCS of the left frontal lobe decreases pathological dysfunction and improves semantic processing of co-verbal gestures in patients with SSD. Methods We measured ratings and reaction times in a speech–gesture semantic relatedness assessment task during application of frontal, frontoparietal, parietal, and sham tDCS to 20 patients with SSD and 29 healthy controls. Results We found a specific effect of tDCS on speech–gesture relatedness ratings of patients. Frontal compared to parietal and sham stimulation significantly improved the differentiation between related and unrelated gestures. Placement of the second electrode (right frontal vs parietal) did not affect the effect of left frontal stimulation, which reduced the preexisting difference between patients and healthy controls. Conclusion Here we show that left frontal tDCS can improve semantic co-verbal gesture processing in patients with SSD. tDCS could be a viable tool to normalize processing in the left frontal lobe and facilitate direct social communicative functioning in patients with SSD.

Multiple studies have sought to characterize the mechanical behavior of callus tissue in vivo during distraction osteogenesis. The aims of such studies are to understand the mechanobiology of distraction and elucidate the complex viscoelasticity and evolution of the tissue. The former objective has direct clinical relevance to surgical technique and process control while the latter is necessary for the calibration and validation of the predictive healing models. Such models seek to reduce the researcher's dependence on animal studies and prospectively allow improved surgical planning. To date, no study has been capable of controlling the mechanical conditions sufficiently enough to decouple the distraction process from the secondary mechanical stimulation associated with the finite stiffness of the fixation constructs employed. It is the goal of this work to understand the mechanobiology of pure distraction as well as characterize viscoelastic tissue behavior under precisely defined mechanical conditions. This is achieved using a novel lateral distraction model. The structural integrity of the bone is maintained, allowing the collection of force relaxation data due to a stepwise distraction process without the superimposed influence of secondary mechanical stimulation. The average instantaneous modulus increases from approximately 2 kPa to approximately 1100 kPa while the equilibrium modulus increases from approximately 0 kPa to 200 kPa over the distraction period.

Some β-mannans, including those in coffee bean and soy, contain a mannose backbone with β-(1→4) bonds. Such mannooligosaccharides could have immunological functions involving direct interaction with immune cells, in addition to acting as prebiotics. This study aimed at assessing the immunological function of mannooligosaccharides with β-(1→4) bond, and elucidating their mechanism of action using bone marrow-derived murine dendritic cells (BMDCs). When BMDCs were stimulated with the mannooligosaccharides, only β-Man-(1→4)-Man significantly induced production of cytokines that included IL-6, IL-10, TNF-α, and IFN-β, and enhanced CD4+ T-cell stimulatory capacity. Use of putative receptor inhibitors revealed the binding of β-Man-(1→4)-Man to TLR4/MD2 complex and involvement with the complement C3a receptor (C3aR) for BMDC activation. Interestingly, β-Man-(1→4)-Man prolonged the production of pro-inflammatory cytokines (IL-6 and TNF-α), but not of the IL-10 anti-inflammatory cytokine during extended culture of BMDCs, associated with high glucose consumption. The results suggest that β-Man-(1→4)-Man is an immunostimulatory molecule, and that the promotion of glycolysis could be involved in the production of pro-inflammatory cytokine in β-Man-(1→4)-Man-stimulated BMDCs. This study could contribute to development of immune-boosting functional foods and a novel vaccine adjuvant.

Purpose To compare measurement precision and interobserver variability in the evaluation of hepatocellular carcinoma (HCC) and liver metastases in MSCT before and after transarterial local ablative therapies. Materials and Methods Retrospective study of 72 patients with malignant liver lesions (42 metastases; 30 HCCs) before and after therapy (43 SIRT procedures; 29 TACE procedures). Established (LAD; SAD; WHO) and vitality-based parameters (mRECIST; mLAD; mSAD; EASL) were assessed manually and semi-automatically by two readers. The relative interobserver difference (RID) and intraclass correlation coefficient (ICC) were calculated. Results The median RID for vitality-based parameters was lower from semi-automatic than from manual measurement of mLAD (manual 12.5 %; semi-automatic 3.4 %), mSAD (manual 12.7 %; semi-automatic 5.7 %) and EASL (manual 10.4 %; semi-automatic 1.8 %). The difference in established parameters was not statistically noticeable (p > 0.05). The ICCs of LAD (manual 0.984; semi-automatic 0.982), SAD (manual 0.975; semi-automatic 0.958) and WHO (manual 0.984; semi-automatic 0.978) are high, both in manual and semi-automatic measurements. The ICCs of manual measurements of mLAD (0.897), mSAD (0.844) and EASL (0.875) are lower. This decrease cannot be found in semi-automatic measurements of mLAD (0.997), mSAD (0.992) and EASL (0.998). Conclusion Vitality-based tumor measurements of HCC and metastases after transarterial local therapies should be performed semi-automatically due to greater measurement precision, thus increasing the reproducibility and in turn the reliability of therapeutic decisions. Key points Citation Format

Perceiving the sensory consequences of one's own actions is essential to successfully interact with the environment. Previous studies compared self- (active) and externally generated (passive) movements to investigate the processing of voluntary action-outcomes. Increased temporal binding (intentional binding) as well as increased detection of delays between action and outcome have been observed for active compared to passive movements. Using transcranial direct stimulation (tDCS) it has been shown that left hemispheric anodal stimulation decreased the intentional binding effect. However, whether the left hemisphere contributes to delay detection performance between action and outcome is unknown. We investigated polarization-dependent effects of left and right frontoparietal tDCS on detecting temporal action-outcome discrepancies. We applied anodal and cathodal stimulation to frontal (F3/F4), parietal (CP3/CP4) and frontoparietal (F3/CP4) areas. After stimulation, participants were presented with visual feedback with various delays after a key press. They had to report whether they detected a delay between the key press and the feedback. In half of the trials the key press was self-initiated, in the other half it was externally generated. A main effect of electrode location indicated highest detection performance after frontal stimulation. Furthermore, we found that the advantage for active versus passive conditions was larger for left hemispheric anodal stimulation as compared to cathodal stimulation. Whereas the frontal cortex is related to delay detection performance in general, hemispheric differences seem to support the differentiation of self-initiated versus externally generated movement consequences.

In polygynandrous mammals, females rarely form affiliative relationships with unrelated males outside the mating context. The antiharassment hypothesis provides one explanation for why such relationships have evolved in some gregarious primates: it states that females receive less aggression from group members in the presence of a male partner and gain his support when being harassed by others. This lowers the costs of competition and increases the female's access to resources, as it also reduces interruptions to feeding. Our aim was to test this hypothesis by investigating the benefits that wild female Assamese macaques, Macaca assamensis, in Thailand derive from bonding with particular males. In support of the antiharassment hypothesis, we found that the strength of affiliative relationships lowered the aggressiveness of a male towards a female, and predicted how much support a female received from a particular male in agonistic interactions with other group members. Additionally, relationship strength predicted the time that females spent co-feeding with a particular male as well as her feeding efficiency in the presence of that male. Hence, female Assamese macaques benefit from forming a social bond with a particular male by reducing the costs of competition.

Background Co-verbal gestures are crucial for communication. Neuroimaging studies suggest that the left frontal lobe may be especially important for processing metaphoric co-verbal gestures. However, so far, the specific functional relevance of the left frontal lobe in metaphoric (abstract sentence content) co-verbal gesture processing compared to iconic (concrete sentence content) co-verbal gesture processing has not been demonstrated. Objective We investigated the functional relevance of the left frontal lobe for processing metaphoric co-verbal gestures using transcranial direct current stimulation (tDCS). We hypothesised a polarisation dependent effect of left frontal tDCS on reaction times and ratings in a speech–gesture semantic relatedness assessment task. Methods We applied anodal, cathodal and sham stimulation to the frontal (F3/F4), parietal (CP3/CP4) and frontoparietal (F3/CP4) areas. During stimulation, seventeen subjects were presented with videos of an actor saying concrete or abstract sentences accompanied by related or unrelated iconic or metaphoric gestures and rated to what extent gestures were related to the sentence content. Results We found electrode localisation- and polarisation-dependent changes in reaction times and ratings for metaphoric co-verbal gestures compared to iconic gestures. Post-hoc tests revealed a specific polarisation effect for frontoparietal stimulation sites: compared to cathodal stimulation, anodal stimulation of the left frontal lobe decreased reaction times and relatedness assessments for metaphoric conditions only. Conclusion Using tDCS, we demonstrated the functional relevance of the left frontal lobe for processing metaphoric co-verbal gestures. Thus, tDCS may possibly constitute an approach to facilitate metaphoric co-verbal gesture-processing in patients with specific deficits.

Background Extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) as respiratory and circulatory assist therapies are gaining in importance in the treatment of critically ill patients. Depending on the place of cannulation – veno-venous for ECMO and veno-arterial for ECLS – distinct changes in hemodynamics will occur. In this review we describe the different types of ECMO and ECLS systems, the typical cannula placement and frequent complications under therapy. The most suitable imaging modalities will be presented and typical hemodynamic pitfalls in contrast-enhanced computed tomography or angiography will be elucidated. Methods The review is based on a literature search in PubMed with the terms “ECMO” and/or “ECLS” and/or “extracorporeal life support” and/or “imaging” and/or “complications”. Statistical data was taken from the ECMO register of the “Extracorporeal Life Support Organization (ELSO)”. Results Critical illness- and therapy-associated complications are common so that imaging, particularly computed tomography, becomes increasingly important. Following veno-venous cannulation in ECMO, the normal sequential blood flow is preserved, so that no contrast enhancement irregularities should be expected when the right timing and an adequate amount of contrast agent are selected. After veno-arterial cannulation in ECLS, different artifacts like pseudo-filling defects, pseudomembranes and irregular/low contrast enhancement of heart and pulmonary vessels can be found, depending on the site of cannulation and the residual cardiac function. Key points Citation Format

Background Coronary artery anomalies encompass a clinically and anatomically variable spectrum including physiological variants and pathophysiologically relevant anomalies. The majority of the variants has no hemodynamic relevance and is often detected accidentally. The recognition of the rare and relevant anomalies that cause either relevant shunt volumes leading to myocardial ischemia or ventricular tachyarrhythmias with the risk of sudden cardiac death is of major importance. Methods This review is based on a literature search in PubMed conducted using the key words “coronary artery” and/or “anomaly” and/or “anomalous origin” and/or “myocardial bridging” and/or “coronary artery fistula” and/or “Bland-White-Garland” and/or “ALCAPA”. Results and Conclusion Coronary artery anomalies can be anatomically subdivided into anomalies of origin, course and termination. The method of choice for anatomical imaging is ECG-triggered or gated multislice CT (MSCT) that provides high spatial resolution and the capability of multiplanar reconstructions. It facilitates the delineation of the precise course of all three coronary arteries and thus allows for correct classification in the anatomical classification system of coronary artery anomalies. The strengths of cardiac magnetic resonance imaging (CMR) are the evaluation of cardiac morphology, myocardial tissue properties and myocardial function. Basic methods are the analysis of myocardial contraction and perfusion with and without pharmacologic stress. Furthermore, potential shunt volumes could be quantified by phase contrast imaging or volumetry. Key points Citation Format

Introduction: Breast cancer is the most common cancer in women. It frequently metastasizes to the lung, liver, and bones. Due to the improvement of therapeutic strategies and therefore longer patient survival, brain metastases have become more frequent. However, evidence-based therapeutic options of systemic treatment are limited because patients with breast cancer brain metastases are often excluded from clinical trials. Case Presentation: Here, we show a patient with brain and orbital metastases from a hormone receptor-positive, Her2neu-negative breast cancer that led to one-sided blindness. She was treated with a combination therapy of the CDK4/6 inhibitor ribociclib and the aromatase inhibitor anastrozole and showed a fast and durable response for 9 months with good tolerability of the treatment. Conclusion: Systemic treatment with a CDK4/6 inhibitor and endocrine therapy can be considered in breast cancer brain metastases.

Rationale and Objectives Congenital heart diseases (CHD) belong to the leading causes of infant mortality worldwide. Prognostic improvements result from multimodal therapy strategies leading to an increased demand for noninvasive imaging. The aim of the study was to further optimize cardiac CT radiation dose by omitting the test bolus or bolus tracking scan, which can have a relevant share of radiation exposure, especially in neonates. Materials and Methods This retrospective study included 25 neonates with CHD who received a CT angiography (CTA) from 2009 to 2018. The examinations were performed as a high-pitch CTA (pitch 3.4, 80 kV) with manual contrast administration (1.5 ml/kg body weight) and fixed scan delay depending on the respective heart defect. Diagnosis, adverse events, radiation dose parameters, objective (contrast-to-noise ratio) and subjective (4-point Likert scale) image quality as well as diagnostic accuracy compared to intraoperative findings was assessed. Results All examinations were diagnostically evaluable without adverse events. The median CT dose index volume (CTDIvol) was 0.50 mGy (range, 0.15–0.94), the median dose-length product was 8 mGy × cm (range, 3–17). The estimation of the effective dose by Monte Carlo simulation revealed lower median dose levels 0.66 mSv (range, 0.25–1.40 mSv) than previously published in comparable groups. All examinations achieved a very good mean image quality score of 1.2 ± 0.4 with only minimal image noise and mean contrast-to-noise ratio of 16.1 ± 7.0. Diagnostic accuracy was 100 % as cardiac anatomy revealed no new diagnoses or significant differences in the subsequent cardiac surgery. Conclusion Cardiac high-pitch CTA of neonates with CHD can be performed safely and dose-reducing without additional test bolus or bolus tracking scan. With very good image quality, it provides a detailed insight into the cardiac anatomy and thus enables a differentiated, noninvasive therapy planning.

Background Preformed nasal endotracheal tubes (NETs) come with a predefined insertion depth due to their curved design. While size indication refers to internal diameter, there is a considerable variability in the corresponding lengths and proportions of same-sized tubes of different manufacturers which is probably based on the lack of data of nasolaryngeal distances (NLDs) in the adult population. Choosing the best-fitting NET is therefore difficult and carries the risk of endobronchial intubation or, on the contrary, cuff inflation at the vocal cord level. The aim of this study was to develop a prediction model for NLD and a selection guide to choose the appropriate NET based on a radiographic description of NLD in comparison to the measurements of available NETs of several manufacturers. Methods After institutional ethics board review, 388 computed tomography (CT) scan images of head, neck, and upper thorax in a heterogeneous adult cohort were included. Mean distances from the nares to the lower border of the thyroid cartilage were measured. NETs from different manufacturers were measured and compared to the NLD derived from the radiographic analysis. The patients' sex, body height, and weight were considered as possible covariates in quantile regression models for predicting the NLD. Results Data from 200 patients were analyzed. NLD was associated with sex, body height, and weight. A simple quantile regression model using the body height as the only covariate sufficed to achieve accurate predictions of NLD. Validation on independent test data showed that 92.8% of the NLD predictions were closer than ±20 mm to the observed NLD values. Measurements of equal-sized NETs varied considerably in outer diameter, proportion, the nasopharyngeal part, and guide marks. Length differences of the bend-to-cuff distance, containing the anatomically NLD, ranged between 218 and 270 mm at same sizes. Conclusions A reliable prediction of NLD can be obtained simply by body height, using the formula (Equation is included in full-text article.). As manufacturers' tube lengths vary substantially, additional information about the bend-to-cuff distance as corresponding tube section would allow for more accurate tube selection.

Food allergies are a steadily increasing health and economic problem. Immunologically, food allergic reactions are caused by pathological, allergen-specific Th2 responses resulting in IgE-mediated mast cell degranulation and associated inflammatory reactions. Clinically, food allergies are characterized by local inflammation of the mouth mucosa, the face, the throat, the gastrointestinal tract, are frequently paralleled by skin reactions, and can result in life-threatening anaphylactic reactions. To better understand food allergies and establish novel treatment options, mouse models are indispensable. This review discusses the available mouse food allergy models, dividing them into four categories: (1) adjuvant-free mouse models, (2) mouse models relying on adjuvants to establish allergen-specific Th2 responses, (3) mouse models using genetically-modified mouse strains to allow for easier sensitization, and (4) humanized mouse models in which different immunodeficient mouse strains are reconstituted with human immune or stem cells to investigate humanized immune responses. While most of the available mouse models can reproducibly portray the immunological parameters of food allergy (Th2 immune responses, IgE production and mast cell activation/expansion), so far, the recreation of the clinical parameters has proven more difficult. Therefore, up to now none of the available mouse models can reproduce the complete human pathology.

Energy availability drives an individual's fitness and can be affected by diverse energetic challenges. The assessment of hormones involved in metabolic activity and energy mobilization provides a gateway to the study of physiological adaptations in response to changes in energy availability. Here, we investigated immunoreactive urinary total triiodothyronine (uTT3, thyroid hormone secreted through the hypothalamus-pituitary-thyroid axis and regulating the basal metabolic rate) alongside glucocorticoids (i.e. urinary cortisol, uCort, secreted through the hypothalamus-pituitary-adrenal axis and mediating energy mobilization) in wild female Assamese macaques (Macaca assamensis). Combining more than 2900; of behavioral data from 42 adult females with physiological data from 382 urine samples, we evaluated both uTT3 and uCort in relation to potential energetic challenges encountered by a female, namely fluctuations in energy intake, travel distance, reproductive state and minimum ambient temperature. As predicted, levels of both hormones changed in response to variation in energy intake with a tendency toward a positive effect on uTT3 and a significant negative effect on uCort levels. Unexpectedly, neither hormone was influenced by variation in travel distance. Reproductive state affected both hormones with higher levels of uTT3 and uCort in the second half of gestation. Finally, a decrease of minimum temperature triggered an increase in uCort but unexpectedly not in uTT3. Collectively, our results highlight the respective contribution of two endocrine axes when facing energetic challenges and the underlying metabolic strategies to cope with them. Overall, assessing thyroid hormones together with glucocorticoids provides an integrative picture in the evaluation of an individual's energy status.

Die immunologischen Untersuchungen in den letzten Jahren haben wesentlich zum Verstandnis der Pathomechanismen von Lebensmittelallergien (Lm-Allergien) beigetragen. Lm-Allergien unterliegen einer komplexen Wechselwirkung des angeborenen und adaptiven Immunsystems, wobei antigenprasentierende Zellen (APC), T‑Zellen, „group 2 innate lymphoid cells“ (ILC2), Epithelzellen (EC) und Effektorzellen interagieren. Epigenetische Faktoren, das intestinale Mikrobiom und Ernahrungsfaktoren, die das gastrointestinale lymphatische Gewebe modulieren, haben wahrscheinlich einen starken Einfluss auf die Entwicklung von Lm-Allergien. Warum einige Individuen Toleranz, andere T‑Helfer-Typ 2(Th2)-Immunantworten entwickeln, welche Faktoren die Allergenitat von Lm-Proteinen definieren und welche immunologischen Mechanismen die Entwicklung einer Lm-Allergie auslosen, bleibt jedoch im Detail zu klaren.

SummaryBackground Non-specific lipid transfer proteins (nsLTP) are considered to provoke allergic symptoms to plane tree pollen, which are frequently associated with peach allergy. Objective The objective was to clone the cDNA of plane pollen nsLTP Pla a 3, to characterize IgE-binding and allergenic potency of recombinant Pla a 3 in comparison to its natural counterpart and peach nsLTP Pru p 3. Methods Natural Pla a 3 was purified from plane pollen and analysed by mass spectrometry (MS). Recombinant Pla a 3 was characterized by SDS-PAGE and CD spectroscopy. Specific IgE to extract, components of plane pollen and Pru p 3 was measured by ImmunoCAP in sera of patients allergic to either plane pollen (n = 10), peach (n = 15) or both (n = 15). Biological potency of the proteins was investigated by in vitro mediator release assays and IgE cross-reactivity by competitive ELISA. Results Two Pla a 3 isoforms were identified. Recombinant Pla a 3 showed high purity, structural integrity, IgE-binding capacity comparable to nPla a 3 and biological potency. Sensitization to plane pollen extract was confirmed in 24/25 plane pollen allergics. The frequency of sensitization to Pla a 3 was 53% among patients allergic to both plane pollen and peach and 10% among plane pollen allergics tolerating peach where most patients were sensitized to Pla a 1. Pla a 3 and Pru p 3 showed strong bi-directional IgE cross-reactivity in patients allergic to peach and plane pollen, but not in peach allergics tolerating plane pollen. Levels of IgE-binding were generally higher to Pru p 3 than to Pla a 3. Conclusion Sensitization to Pla a 3 is relevant in a subgroup of plane pollen allergics with concomitant peach allergy. IgE testing with Pla a 3 may serve as a marker to identify plane pollen allergic patients at risk of LTP-mediated food reactions and thereby improve in vitro diagnostic procedures.

Mammals living in stable social groups often mitigate the costs of group living through the formation of social bonds and cooperative relationships. The neuropeptide hormone oxytocin (OT) has been proposed to promote both bonding and cooperation although only a limited number of studies have investigated this under natural conditions. Our aim was to assess the role of OT in bonding and cooperation in male Barbary macaques (Macaca sylvanus). First we tested for an effect of affiliation - grooming and triadic male-infant-male interactions - with bond and non-bond partners on urinary OT levels. Secondly we aimed to test whether grooming interactions (and thus increased OT levels) increase a male’s general propensity to cooperate in polyadic conflicts. We collected behavioral data via full-day focal animal protocols on 14 adult males and measured endogenous OT levels from 139 urine samples collected after affiliation and non-social control periods. Urinary OT levels were higher after grooming with any partner. By contrast, OT levels after male-infant-male interactions with any partner or with bond partners were not different from controls but were higher after interactions with non-bond partners. Previous grooming did not increase the likelihood of males to support others in conflicts. Collectively, our results support research indicating that OT is involved in the regulation of adult social bonds, including in non-reproductive contexts. However, our male-infant-male interaction results go against previous studies suggesting that it is affiliation with bond rather than non-bond partners that trigger the release of OT. Alternatively, OT levels may have been elevated prior to male-infant-male interactions thus facilitating interaction between non-bond partners. The lack of an association of grooming (and by extension increased OT levels) and subsequent support speaks against an OT linked increase in the general propensity to cooperate, yet further studies are needed for a more direct test including the possibility of partner-specific contingent cooperation.

Utilization of virus-like particles (VLPs) is considered to improve allergen-specific immunotherapy (AIT). AIT aims at the efficient uptake of the target allergen by antigen-presenting cells (APCs) subsequently inducing adaptive allergen-specific immune responses to induce tolerance. The purpose of this review is to describe the immune-modulating properties of VLPs per se and to summarize the application of VLPs as antigen carriers, preferably for Th2 cytokines or allergens, with and without simultaneous administration of adjuvants in order to modulate allergic immune responses. Currently, a broad variety of approaches considering the origin of the VLPs, the choice of the adjuvant and antigen, and the coupling of the antigen are under preclinical investigation. The data provide evidence that VLPs used as carrier for antigens/allergens strongly increase antigen immunogenicity, and might be suitable to prevent allergies. However, systematic studies in mice showing the immunological mechanism and data from clinical studies are scarce.

Humans share an extraordinary degree of sociality with other primates, calling for comparative work into the evolutionary drivers of the variation in social engagement observed between species. Of particular interest is the contrast between the chimpanzee (Pan troglodytes) and bonobo (Pan paniscus), the latter exhibiting increased female gregariousness, more tolerant relationships, and elaborate behavioral adaptations for conflict resolution. Here, we test predictions from 3 socioecological hypotheses regarding the evolution of these traits using data on wild bonobos at LuiKotale, Democratic Republic of Congo. Focusing on the behavior of co-feeding females and controlling for variation in characteristics of the feeding patch, food intake rate moderately increased while feeding effort decreased with female dominance rank, indicating that females engaged in competitive exclusion from high-quality food resources. However, these rank effects did not translate into variation in energy balance, as measured from urinary C-peptide levels. Instead, energy balance varied independent of female rank with the proportion of fruit in the diet. Together with the observation that females join forces in conflicts with males, our results support the hypothesis that predicts that females trade off feeding opportunities for safety against male aggression. The key to a full understanding of variation in social structure may be an integrated view of cooperation and competition over access to the key resources food and mates, both within and between the sexes.

As dental imaging accounts for approximately 40 % of all X-ray examinations in Germany, profound knowledge of this topic is essential not only for the dentist but also for the clinical radiologist. This review focuses on basic imaging findings regarding the teeth. Therefore, tooth structure, currently available imaging techniques and common findings in conserving dentistry including endodontology, periodontology, implantology and dental trauma are presented. Literature research on the current state of dental radiology was performed using Pubmed. Currently, the most frequent imaging techniques are the orthopantomogram (OPG) and single-tooth radiograph, as well as computer tomography (CT) and cone beam CT mainly for implantology (planning or postoperative control) or trauma indications. Especially early diagnosis and correct classification of a dental trauma, such as dental pulp involvement, prevents from treatment delays or worsening of therapy options and prognosis. Furthermore, teeth are commonly a hidden focus of infection.Since radiologists are frequently confronted with dental imaging, either concerning a particular question such as a trauma patient or regarding incidental findings throughout head and neck imaging, further training in this field is more than worthwhile to facilitate an early and sufficient dental treatment. · This review focuses on dental imaging techniques and the most important pathologies.. · Dental pathologies may not only be locally but also systemically relevant.. · Reporting of dental findings is important for best patient care..· Masthoff M, Gerwing M, Masthoff M et al. Dental Imaging - A basic guide for the radiologist. Fortschr Röntgenstr 2019; 191: 192 - 198. Da die dentale Bildgebung etwa 40 % aller Röntgenuntersuchungen in Deutschland ausmacht, sind fundierte Kenntnisse für den klinischen Radiologen auf diesem Gebiet essenziell. Der Fokus dieser Übersichtsarbeit liegt auf der Bildgebung des Zahnes. Hierfür werden Zahnaufbau, derzeit verfügbare Bildgebungstechniken und häufige Befunde der konservierenden Zahnheilkunde einschließlich der Endodontologie, Parodontologie und der Implantologie sowie nach dentalem Trauma vorgestellt. Es erfolgte eine Literaturrecherche zur dentalen Radiologie mittels Pubmed. Bildgebungstechniken erster Wahl sind weiterhin das Orthopantomogramm (OPG) sowie die Einzelzahnaufnahme. Ergänzend werden die Computertomografie (CT) und die digitale Volumentomografie (DVT), vorrangig für die Implantologie (Behandlungsplanung und Verlaufskontrolle) oder verunfallte Patienten, eingesetzt. Insbesondere beim dentalen Trauma vermeidet eine exakte Diagnostik und korrekte Klassifikation, beispielsweise bezüglich einer Beteiligung der Zahnpulpa, Therapieverzögerungen oder deren Prognoseverschlechterung. Zudem können Zähne einen häufigen Infekt-Fokus darstellen.Da Radiologen häufig mit der dentalen Bildgebung konfrontiert werden, sei es als dezidierte Fragestellung bei einem Trauma-Patienten oder bei Zufallsbefunden im Rahmen der Kopf-/ Halsbildgebung, ist eine „Blickschulung“ für häufige Befunde lohnenswert, um frühzeitig eine suffiziente zahnärztliche Behandlung zu bahnen. · Dieser Review behandelt die dentalen Bildgebungstechniken sowie die wichtigsten Zahnpathologien.. · Zahnpathologien können nicht nur lokal, sondern auch systemisch relevant sein.. · Dentale Befunde sollten für eine bestmögliche Patientenversorgung Teil der Befundung sein..· Masthoff M, Gerwing M, Masthoff M et al. Dental Imaging - A basic guide for the radiologist. Fortschr Röntgenstr 2019; 191: 192 – 198.

Non-specific lipid-transfer proteins (nsLTPs) represent a family of ubiquitous plant proteins belonging to the prolamin superfamily. nsLTPs are characterized by a globular α-helical structure stabilized by four disulfide bonds and a hydrophobic cavity which acts as ligand-binding site for a broad spectrum of lipids and hydrophobic molecules. nsLTPs are involved in membrane biogenesis and in the adaption of plants to abiotic and biotic stress. They display antimicrobial activity by the ability to permeabilize the cell membrane of phytopathogens. Moreover, in the presence of lipids, nsLTPs are suggested to activate the plant immune system by a receptor-dependent mechanism. Additionally, nsLTPs from pollen and plant-derived food, in particular type 1 nsLTPs (9 kDa), are described as potent allergens. Within the nsLTP family Pru p 3 from peach is the clinically most relevant allergen which can cause genuine food allergy and frequently elicits severe clinical reactions. So far, the allergenic properties of nsLTPs are attributed to both their low molecular mass and their high thermal and proteolytic stability which allow them to reach the immune system in a biological intact form. Recently, the interaction of nsLTPs with lipids has been suggested to increase their allergenic properties and to promote the allergic sensitization to these proteins. This review will summarize the current knowledge on diversity of lipid ligands of plant LTPs, and illustrate recent studies performed with allergenic nsLTPs to investigate the effect of lipid binding on the structural modification and IgE-binding properties of proteins, and finally the potential effect on the innate immune responses.

Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens in order to prevent chronic inflammation and tissue damage. Because of their important role in preventing autoimmune diseases, transplant rejection, allergic reactions, or in controlling chronic inflammation DCs have become an interesting tool to modulate antigen-specific immune responses. For the treatment of allergic inflammation, the aim is to down-regulate allergen-specific T helper 2 (Th2)-responses and the associated clinical symptoms (allergen-driven Th2 activation, Th2-driven immunoglobulin E (IgE)-production, IgE-mediated mast cell and basophil activation, allergic inflammation). Here, combining the presentation of allergens by DCs with a pro-tolerogenic, IL-10-producing phenotype is of special interest to modulate allergen-specific immune responses in the treatment of allergic diseases. This review discusses the reported strategies to induce DC-derived IL-10 secretion for the suppression of allergen-specific Th2-responses with a focus on IL-10 treatment, IL-10 transduction, and the usage of both whole bacteria and bacteria-derived components. Interestingly, while IL-10-producing DCs induced either by IL-10-treatment or IL-10 transduction are arrested in an immature/semi-mature state, treatment of DCs with live or killed bacteria as well as isolated bacterial components results in the induction of both anti-inflammatory IL-10- as well as pro-inflammatory, Th1-promoting IL-12 secretion often paralleled by an enhanced expression of co-stimulatory molecules on the stimulated DCs. By the secretion of DC-derived exosomes or CC-chemokine ligand 18 (CCL18), as well as the expression of inhibitory molecules like cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), TNF receptor superfamily member 4 (OX40), Ig-like transcript-22/CD85, or programmed death-1 (PD-1), IL-10-producing DCs have been repeatedly shown to suppress antigen-specific Th2-responses. Therefore, DC-based vaccination approaches hold great potential improve the treatment of allergic diseases.