A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms.

While oncotherapy has made rapid progress in recent years, side effects of anti-cancer drugs and treatments have also come to the fore. These side effects include cardiotoxicity, which can cause irreversible cardiac damages with long-term morbidity and mortality. Despite the continuous in-depth research on anti-cancer drugs, an improved knowledge of the underlying mechanisms of cardiotoxicity are necessary for early detection and management of cardiac risk. Although most reviews focus on the cardiotoxic effect of a specific individual chemotherapeutic agent, the aim of our review is to provide comprehensive insight into various agents that induced cardiotoxicity and their underlying mechanisms. Characterization of these mechanisms are underpinned by research on animal models and clinical studies. In order to gain insight into these complex mechanisms, we emphasize the role of inflammatory processes and oxidative stress on chemotherapy-induced cardiac changes. A better understanding and identification of the interplay between chemotherapy and inflammatory/oxidative processes hold some promise to prevent or at least mitigate cardiotoxicity-associated morbidity and mortality among cancer survivors.

Sharing and Receiving Eye-Contact Predicts Mate Choice After a 5-Minute Conversation: Evidence from a Speed-Dating Study.

In popular narratives, the first date with a potential mate often centers on their gaze as embodiment of interest and attraction. However, evidence is still lacking on the role of eye-contact as a potent signal in human social interaction in the context of dating. In addition, behavioral mechanisms of mate selection are not well understood. In the present study, we therefore examined mutual eye-contact and its influence on mate choice by applying dual mobile eye-tracking during naturalistic speed-dates. A total of 30 male and 30 female subjects attended four speed-dates each (N = 240). Subjects were more likely to choose those dating partners with whom they shared more eye-contact with. In addition, perceived attractiveness played an important role for mate choice. Interestingly, receiving but not giving eye-contact also predicted individual mate choice. Eye-contact thus acts as an important signal of romantic attraction when encountering a dating partner.

Variation in antisaccadic response latencies investigated with the hierarchical LATER process model.

The antisaccade paradigm is frequently applied to measure inhibitory control. Typically, simple, perceptually neutral stimuli are used as cues. Recently, emotional versions of this paradigm have also been employed. In our study, we used both versions of the paradigm. In addition, scrambled faces served to control for stimulus size and emotional valence. We applied a hierarchical extension to the Linear Approach to Threshold Ergodic Rate (LATER) process model, which allows the estimation of two latent cognitive parameters: speed of information accumulation (accretion rate) and the amount of information needed before a saccadic movement (caution threshold). We hypothesized a faster accretion rate and lower caution threshold for circular and scrambled compared to emotional face stimuli as well as meaningful differences between individual emotions. Our results showed a faster accretion rate and lower caution threshold for emotional compared to circular stimuli, though. In contrast, scrambled faces had a lower accretion rate and lower caution threshold. Furthermore, the LATER model uncovered subtle differences between different emotions. Happy faces tend to receive a faster accretion rate and higher caution threshold than neutral ones, while for fearful faces it was the other way around. Our results contradict earlier research on emotional stimuli interfering inhibitory control.

Do emotional stimuli interfere with response inhibition? evidence from the antisaccade paradigm.

When it comes to measuring cognitive control and inhibition, the antisaccade paradigm is a popular task to apply. Usually, simple, perceptually and affectively neutral stimuli, e.g. white circles, are used. Recently, researchers also employed a version of the paradigm displaying emotional faces. Differences in cognitive processing due to stimulus size and emotional valence have not been investigated yet. Thus, in the present study, we applied both versions of the antisaccade paradigm in a healthy sample. In addition, we used scrambled faces to control for stimulus size and emotional valence. We hypothesised slower reaction times and higher error rates for emotional face stimuli compared to circular and scrambled ones as well as significant differences between individual emotions. In contrast to our hypotheses, results showed faster reaction times fewer errors for emotional faces compared to circular and scrambled stimuli. Furthermore, ANOVA models showed no meaningful differences between different emotions. Our study shows specific patterns in inhibitory control due to stimulus size and valence in an antisaccade eye-tracking task.

[Recording of SARS-CoV-2 laboratory tests in Germany]. / Erfassung der Labortestungen auf SARS-CoV-2 in Deutschland.

The collection of data on SARS-CoV­2 tests is central to the assessment of the infection rate in the context of the COVID-19 pandemic. At the Robert Koch Institute (RKI), data collected from various laboratory data recording systems are consolidated. First, this article aims to exemplify significant aspects regarding test procedures. Subsequently the different systems for recording laboratory tests are described and test numbers from the RKI test laboratory query and the laboratory-based SARS-CoV­2 surveillance as well as accounting data from the Association of Statutory Health Insurance Physicians for SARS-CoV­2 laboratory tests are shown.Early in the pandemic, the RKI test laboratory query and the laboratory-based SARS-CoV­2 surveillance became available and able to evaluate data on performed tests and test capacities. By recording the positive and negative test results, statements about the total number of tests and the proportion of positive test rates can be made. While the aggregate test numbers are largely representative nationwide, they are not always representative at the state and district level. The billing data of the Association of Statutory Health Insurance Physicians can complement the laboratory data afterwards. In addition, it can provide a retrospective assessment of the total number of SARS-CoV­2 numbers in Germany, because the services provided by statutory health insurers (around 85% of the population in Germany) are included. The various laboratory data recording systems complement one another and the evaluations flow into the recommended measures for the pandemic response.

A Potential Involvement of Anandamide in the Modulation of HO/NOS Systems: Women, Menopause, and "Medical Cannabinoids".

Endocannabinoids and their receptors are present in the cardiovascular system; however, their actions under different pathological conditions remain controversial. The aim of our study was to examine the effects of anandamide (AEA) on heme oxygenase (HO) and nitric oxide synthase (NOS) systems in an estrogen-depleted rat model. Sham-operated (SO) and surgically induced estrogen-deficient (OVX) female Wistar rats were used. During a two-week period, a group of OVX rats received 0.1 mg/kg estrogen (E2) per os, while AEA-induced alterations were analyzed after two weeks of AEA treatment at the dose of 1.0 mg/kg. At the end of the experiment, cardiac activity and expression of HO and NOS enzymes, content of cannabinoid 1 receptor, as well as concentrations of transient potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) were measured. Our results show that estrogen withdrawal caused a significant decrease in both NOS and HO systems, and a similar tendency was observed regarding the TRPV1/CGRP pathway. Two weeks of either AEA or E2 treatment restored the adverse changes; however, the combined administration of these two molecules did not result in a further improvement. In light of the potential relationship between AEA and HO/NOS systems, AEA-induced upregulation of HO/NOS enzymes may be a therapeutic strategy in estrogen-deficient conditions.

Cerebral blood flow responses during prosaccade and antisaccade preparation in major depression.

While impairments in executive functions have been well established in major depressive disorder (MDD), specific deficits in proactive control have scarcely been studied so far. Proactive control refers to cognitive processes during anticipation of a behaviorally relevant event that facilitate readiness to react. In this study, cerebral blood flow responses were investigated in MDD patients during a precued antisaccade task requiring preparatory attention and proactive inhibition. Using functional transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 40 MDD patients and 40 healthy controls. In the task, a target appeared left or right of the fixation point 5 s after a cuing stimulus; subjects had to move their gaze to the target (prosaccade) or its mirror image position (antisaccade). Video-based eye-tracking was applied for ocular recording. A right dominant blood flow increase arose during prosaccade and antisaccade preparation, which was smaller in MDD patients than controls. Patients exhibited a higher error rate than controls for antisaccades but not prosaccades. The smaller blood flow response may reflect blunted anticipatory activation of the dorsolateral prefrontal and inferior parietal cortices in MDD. The patients' increased antisaccade error rate suggests deficient inhibitory control. The findings support the notion of impairments in proactive control in MDD, which are clinically relevant as they may contribute to the deficits in cognition and behavioral regulation that characterize the disorder.

The Anti-Inflammatory Role of Mannich Curcuminoids; Special Focus on Colitis.

The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-κB (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-κB-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-κB inhibition with 3.57 µM or 1.6 µM half maximal effective concentration (EC50) values, respectively. C150 exerted a profound inhibition of the expression of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-4 (IL-4) in human PBMCs (peripheral blood mononuclear cells) upon LPS stimulus. Mannich curcuminoids reported herein possess a powerful anti-inflammatory activity.

Cerebral blood flow modulations during proactive control in chronic hypotension.

In addition to complaints including fatigue, mood disturbance, dizziness or cold limbs, chronic low blood pressure (hypotension) is associated with reduced cognitive performance. Deficiencies in cerebral blood flow regulation may contribute to this impairment. This study investigated cerebral blood flow modulations during proactive control in hypotension. Proactive control refers to cognitive processes during anticipation of a behaviourally relevant event that allow optimization of readiness to react. Using functional transcranial Doppler sonography, bilateral blood flow velocities in the middle cerebral arteries were recorded in 40 hypotensive and 40 normotensive participants during a precued Stroop task. Hypotensive participants exhibited smaller bilateral blood flow increases during response preparation and longer response time. The group differences in blood flow and response time did not vary by executive function load, i.e. congruent vs. incongruent trials. Over the total sample, the flow increase correlated negatively with response time in trials with a higher executive function load. The findings indicate reduced cerebral blood flow adjustment during both the basic and more complex requirements of proactive control in hypotension. They also suggest a general deficit in attentional function and processing speed due to low blood pressure and cerebral hemodynamic dysregulations rather than particular impairments in executive functions.

Autonomic Cardiovascular Control and Executive Function in Chronic Hypotension.

BACKGROUND: Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition. PURPOSE: The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension. METHODS: Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task). Parameters of cardiac sympathetic control, i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance, and parasympathetic control, i.e., respiratory sinus arrhythmia and baroreflex sensitivity, were obtained. RESULTS: The hypotensive group exhibited lower stroke volume and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity during task execution. Increased error rates in hypotensive individuals were observed in the n-back and flanker tasks. In the total sample, there were positive correlations of error rates with pre-ejection period, baroreflex sensitivity and respiratory sinus arrhythmia, and negative correlations with cardiac output. CONCLUSIONS: Group differences in stroke volume, cardiac output, and pre-ejection period suggest diminished beta-adrenergic myocardial drive during executive function processing in hypotension, in addition to increased baroreflex function. Although further research is warranted to quantify the extent of executive function impairment in hypotension, the results from correlation analysis add evidence to the notion that higher sympathetic inotropic influences and reduced parasympathetic cardiac influences are accompanied by better cognitive performance.

Executive function and cardiac autonomic regulation in depressive disorders.

Executive function impairments have been frequently observed in depressive disorders. Moreover, reduced heart rate variability (HRV) has repeatedly been described, especially in the high frequency band (i.e., respiratory sinus arrhythmia, RSA), suggesting lower vagal cardiac outflow. The study tested the hypothesis of involvement of low vagal tone in executive dysfunction in depression. In addition to RSA, HRV in the low frequency (LF) band was assessed. In 36 patients with depression and 36 healthy subjects, electrocardiography recordings were accomplished at rest and during performance of five executive function tasks (number-letter task, n-back task, continuous performance test, flanker task, and antisaccade task). Patients displayed increased error rates and longer reaction times in the task-switching condition of the number-letter task, in addition to increased error rates in the n-back task and the final of two blocks of the antisaccade task. In patients, both HRV parameters were lower during all experimental phases. RSA correlated negatively with reaction time during task-switching. This finding confirms reduced performance across different executive functions in depression and suggests that, in addition to RSA, LF HRV is also diminished. However, the hypothesis of involvement of low parasympathetic tone in executive dysfunction related to depression received only limited support.

Large measles outbreak introduced by asylum seekers and spread among the insufficiently vaccinated resident population, Berlin, October 2014 to August 2015.

The largest measles outbreak in Berlin since 2001 occurred from October 2014 to August 2015. Overall, 1,344 cases were ascertained, 86% (with available information) unvaccinated, including 146 (12%) asylum seekers. Median age was 17 years (interquartile range: 4-29 years), 26% were hospitalised and a 1-year-old child died. Measles virus genotyping uniformly revealed the variant 'D8-Rostov-Don' and descendants. The virus was likely introduced by and initially spread among asylum seekers before affecting Berlin's resident population. Among Berlin residents, the highest incidence was in children aged < 2 years, yet most cases (52%) were adults. Post-exposure vaccinations in homes for asylum seekers, not always conducted, occurred later (median: 7.5 days) than the recommended 72 hours after onset of the first case and reached only half of potential contacts. Asylum seekers should not only have non-discriminatory, equitable access to vaccination, they also need to be offered measles vaccination in a timely fashion, i.e. immediately upon arrival in the receiving country. Supplementary immunisation activities targeting the resident population, particularly adults, are urgently needed in Berlin.

Genetic diversity and distribution patterns of diploid and polyploid hybrid water frog populations (Pelophylax esculentus complex) across Europe.

Polyploidization is a rare yet sometimes successful way for animals to rapidly create geno- and phenotypes that may colonize new habitats and quickly adapt to environmental changes. In this study, we use water frogs of the Pelophylax esculentus complex, comprising two species (Pelophylax lessonae, genotype LL; Pelophylax ridibundus, RR) and various diploid (LR) and triploid (LLR, LRR) hybrid forms, summarized as P. esculentus, as a model for studying recent hybridization and polyploidization in the context of speciation. Specifically, we compared the geographic distribution and genetic diversity of diploid and triploid hybrids across Europe to understand their origin, maintenance and potential role in hybrid speciation. We found that different hybrid and parental genotypes are not evenly distributed across Europe. Rather, their genetic diversity is structured by latitude and longitude and the presence/absence of parental species but not of triploids. Highest genetic diversity was observed in central and eastern Europe, the lowest in the northwestern parts of Europe. This gradient can be explained by the decrease in genetic diversity during postglacial expansion from southeastern glacial refuge areas. Genealogical relationships calculated on the basis of microsatellite data clearly indicate that hybrids are of multiple origin and include a huge variety of parental genomes. Water frogs in mixed-ploidy populations without any parental species (i.e. all-hybrid populations) can be viewed as evolutionary units that may be on their way towards hybrid speciation. Maintenance of such all-hybrid populations requires a continuous exchange of genomes between diploids and triploids, but scenarios for alternative evolutionary trajectories are discussed.

Swift attenuation of irrelevant features through feature consistency: Evidence from a capture-probe version of the contingent-capture protocol.

In the present two experiments, we explore the possibility of swift attenuation of capture by irrelevant features in the contingent-capture protocol. Some prior research suggests that feature attenuation might be most efficient for fixed, anticipated irrelevant features and that varying irrelevant features from trial to trial can undermine their successful attenuation. Here, we exploited this dependence of attenuation on feature certainty to test if attenuation contributed to contingent-capture effects in a capture-probe version of the contingent-capture protocol. In line with the swift attenuation of irrelevant features, salient but target-dissimilar singleton cues that were consistently coloured diminished recall of probes at their locations. This was in comparison to inconsistently coloured target-dissimilar singleton cues. Nonetheless, probe-recall was still better at target-dissimilar cue locations than at non-singleton locations in the cueing display, indicating attenuation of task-irrelevant features rather than their complete suppression.

Mechanisms and Target Parameters in Relation to Polycystic Ovary Syndrome and Physical Exercise: Focus on the Master Triad of Hormonal Changes, Oxidative Stress, and Inflammation.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females of reproductive age with heterogeneous prevalence. It is well known that female reproductive competence depends on the dynamic regulation of the hypothalamic-pituitary-gonadal (HPG) axis; therefore, disruption of this highly regulated system leads to fertility problems. Among disruptors, both oxidative stress and inflammation contribute to an increased LH-FSH ratio and a consequent hyperandrogenism. Shifts in this bidirectional interplay between the neuroendocrine system and oxidative/inflammatory homeostasis result in the accumulation of reactive oxygen/nitrogen species and inflammatory markers as well as alterations in antioxidant defense mechanisms. Evidence shows that lifestyle changes, including regular physical exercise, are recognized as the most effective first-line management to reduce the severity of PCOS symptoms. The aim of our narrative review is to provide insights into the mechanisms and target factors of PCOS-related hormonal changes, oxidative/antioxidant homeostasis, and inflammation, and to discuss the effects of exercise, which takes into account various factors, in relation to PCOS. A better understanding of the PCOS-associated hormonal changes, oxidative and inflammatory circuits, as well as exercise-induced mechanisms of action on those targets may improve the quality of life of women with PCOS.

Emotion Recognition in Multiple System Atrophy: An Exploratory Eye-Tracking Study.

OBJECTIVE: Emotional processing is a core feature of social interactions and has been well studied in patients with idiopathic Parkinson's disease (PD), albeit with contradictory. RESULTS: . However, these studies excluded patients with atypical parkinsonism, such as multiple system atrophy (MSA). The objective of this exploratory study was to provide better insights into emotion processing in patients with MSA using eye tracking data. METHODS: We included 21 MSA patients, 15 PD patients and 19 matched controls in this study. Participants performed a dynamic and a static emotion recognition task, and gaze fixations were analyzed in different areas of interest. Participants underwent neuropsychological testing and assessment of depression and alexithymia. RESULTS: MSA patients were less accurate in recognizing anger than controls (p = 0.02) and had overall fewer fixations than controls (p = 0.001). In the static task, MSA patients had fewer fixations (p < 0.001) and a longer time to first fixation (p = 0.026) on the eye region. Furthermore, MSA patients had a longer fixation duration overall than PD patients (p = 0.004) and longer fixations on the nose than controls (p = 0.005). Alexithymia scores were higher in MSA patients compared to controls (p = 0.038). CONCLUSION: This study demonstrated impaired recognition of anger in MSA patients compared to HCs. Fewer and later fixations on the eyes along with a center bias suggest avoidance of eye contact, which may be a characteristic gaze behavior in MSA patients.

Genomic effects on advertisement call structure in diploid and triploid hybrid waterfrogs (Anura, Pelophylax esculentus).

BACKGROUND: In anurans, differences in male mating calls have intensively been studied with respect to taxonomic classification, phylogeographic comparisons among different populations and sexual selection. Although overall successful, there is often much unexplained variation in these studies. Potential causes for such variation include differences among genotypes and breeding systems, as well as differences between populations. We investigated how these three factors affect call properties in male water frogs of Pelophylax lessonae (genotype LL), P. ridibundus (RR) and their interspecific hybrid P. esculentus which comes in diploid (LR) and triploid types (LLR, LRR). RESULTS: We investigated five call parameters that all showed a genomic dosage effect, i.e. they either decreased or increased with the L/R ratio in the order LL-LLR-LR-LRR-RR. Not all parameters differentiated equally well between the five genotypes, but combined they provided a good separation. Two of the five call parameters were also affected by the breeding system. Calls of diploid LR males varied, depending on whether these males mated with one or both of the parental species (diploid systems) or triploid hybrids (mixed ploidy systems). With the exception of the northernmost mixed-ploidy population, call differences were not related to the geographic location of the population and they were not correlated with genetic distances in the R and L genomes. CONCLUSIONS: We found an influence of all three tested factors on call parameters, with the effect size decreasing from genotype through breeding system to geographic location of the population. Overall, results were in line with predictions from a dosage effect in L/R ratios, but in three call parameters all three hybrid types were more similar to one or the other parental species. Also calls of diploid hybrids varied between breeding systems in agreement with the sexual host required for successful reproduction. The lack of hybrid call differences in a mixed-ploidy population at the northern edge of the water frog distribution is likely to be associated with genetic particularities, including a) low genetic variability and/or b) a local loss of genes coding for genotype-dependent call differentiation under conditions where female discrimination between diploid and triploid males is not beneficial.

Systematic review of time lag between antibiotic use and rise of resistant pathogens among hospitalized adults in Europe.

Background: Antimicrobial resistance (AMR) causes substantial health and economic burden to individuals, healthcare systems and societies globally. Understanding the temporal relationship between antibiotic consumption and antibiotic resistance in hospitalized patients can better inform antibiotic stewardship activities and the time frame for their evaluation. Objectives: This systematic review examined the temporal relationship between antibiotic use and development of antibiotic resistance for 42 pre-defined antibiotic and pathogen combinations in hospitalized adults in Europe. Methods: Searches in MEDLINE, Embase, Cochrane Library and NIHR Centre for Reviews and Dissemination were undertaken from 2000 to August 2021. Pathogens of interest were Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecium, CoNS, Pseudomonas aeruginosa and Acinetobacter baumannii complex. Results: Twenty-eight ecological studies and one individual-level study were included. Ecological studies were predominantly retrospective in design (19 studies) and of reasonable (20 studies) to high (8 studies) methodological quality. Of the eight pathogens of interest, no relevant data were identified for S. pneumoniae and CoNS. Across all pathogens, the time-lag data from the 28 ecological studies showed a similar pattern, with the majority of studies reporting lags ranging from 0 to 6 months. Conclusions: Development of antibiotic resistance for the investigated antibiotic/pathogen combinations tends to occur over 0 to 6 months following exposure within European hospitals. This information could inform planning of antibiotic stewardship activities in hospital settings.

The Interplay of Lifestyle and Adipokines in the Non-Obese Stroke-Prone Spontaneously Hypertensive Rats.

Although the morphological features and functions of adipose tissue are well-described in obesity-prone animal models, less information is available on animals such as the stroke-prone spontaneously hypertensive (SHRSP) strain with cardiovascular abnormalities, which is not characterized by excessive adiposity. Our aim was to focus on lifestyle-induced (type of diet and physical exercise) effects on adipokine profile and lipid peroxidation in SHRSP rats. In our study, male Wistar-kyoto (control) and SHRSP rats were used. SHRSP rats were fed either standard chow or a high-fat diet with 40% fat content (HFD). One group of the animals was placed into cages fitted with a running-wheel; thus, the dietary and training period started at the same time and lasted for 12 weeks. At the end of the experimental period, adiponectin, leptin, omentin, and chemerin concentrations were determined from adipose tissue and serum. Besides adipokines, malondialdehyde (MDA) levels were also measured. Twelve weeks of HFD significantly decreased adiponectin and omentin concentrations of both adipose tissue and serum, which were ameliorated by physical exercise. Serum leptin, chemerin, and MDA values were elevated in HFD groups; however, physical exercise was able to mitigate these adverse changes. Our results underpin the crosstalk between lifestyle changes and dysfunctional adipose tissue in SHRSP rats.