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Background: Women developing preeclampsia (PE) or fetal growth restriction (FGR) during pregnancy are at higher risk for cardiovascular diseases (CVD) later in life. We aimed to analyse cardiovascular health of women 10-20 years after affected pregnancies in comparison to women after uneventful pregnancies. In addition, we assessed a potential long-term effect of the NO-donor pentaerythrityl tetranitrate (PETN)., Methods: Women 10-20 years after severe PE, including women receiving PETN during pregnancy and matched controls were recruited and assessed for baseline clinical data and cardiovascular function by transthoracic echocardiography, VICORDER and USCOM. SPSS was used for statistical analysis., Results: 53 participants after PE/FGR (13 with former PETN intake) and 51 controls were recruited for follow-up at an average of 14 years after index pregnancies. Compared to controls, women after PE/FGR had a significantly higher incidence of arterial hypertension (13.7% vs. 41.5%, p<0.001), and were more likely to be hypertensive (41.2% vs. 67.30%, p = 0.008). There were no differences in cardiovascular function observed. Affected women with PETN intake during pregnancy showed lower mean values for right atrial area and ventricle in comparison to controls and also to affected women without former medication., Conclusions: In conclusion, our study results confirm that the risk of CVD is increased in women after PE/FGR compared to women after uneventful pregnancies. Contrary to our expectations, no major cardiovascular changes were observed in our cohort 10-20 years post pregnancy. The observed differences found in right heart dimensions were within reference ranges, and should be interpreted with caution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lößner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Facial nerve palsy (FP) is the most common cranial nerve lesion, leading to partial or complete immobility of the affected half of face. If food residues on tooth surfaces cannot be removed by natural self-cleaning mechanisms that this is likely to lead to an increase dental plaque formation and the risk of dental, periodontal and general diseases. It was the aim of this study to assess oral health, oral hygiene with the influence of handedness and oral health related quality of life in patients with chronic peripheral FP. This study included 86 people. Patients with FP (n = 43) in an FP-group (FPG) were matched with 43 participants without ever diagnosed FP in a control group (CG). Oral health and oral hygiene were assessed in a clinical examination performed in hospital. Decayed-missing-filled-teeth-index, periodontal-screening-index, approximal plaque index and sulcus bleeding index were used to evaluate dental caries and periodontal health status. Oral health-related quality of life data (OHQoL) was collected with the Oral health impact profile (Germany-14) by interview. Oral health parameters in the FPG were significantly worse than in the CG. The median revealed 14.3% more proximal plaque (p = 0.014), 20.8% more sulcus bleeding (p = 0.002) and more than twice as much caries (p = 0.024). The paretic side compared to the non-paretic side of patients was significantly more affected by inflammatory periodontal diseases (p = 0.032) and had a higher prevalence of caries (p = 0.163). Right-handed patients with right-sided FP performed worse than right-handed patients with left-sided FP (p = 0.004). Patients with FP described a greater limitation of OHQoL than patients without this disease (p &lt; 0.001). In conclusion, facial nerve palsy affects oral health, oral hygiene and OHQoL of patients while handedness influences oral hygiene and oral health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Strobelt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To develop multidimensional approaches for pain management, this study aimed to understand how PD patients cope with pain., Design: Cross-sectional, cohort study., Setting: Monocentric, inpatient, university hospital., Participants: 52 patients with Parkinson's disease (without dementia) analysed., Primary and Secondary Outcome Measures: Motor function, nonmotor symptoms, health-related quality of life (QoL), and the Coping Strategies Questionnaire were assessed. Elastic net regularization and multivariate analysis of variance (MANOVA) were used to study the association among coping, clinical parameters, and QoL., Results: Most patients cope with pain through active cognitive (coping self-statements) and active behavioral strategies (increasing pain behaviors and increasing activity level). Active coping was associated with lower pain rating. Regarding QoL domains, active coping was associated with better physical functioning and better energy, whereas passive coping was associated with poorer emotional well-being. However, as demonstrated by MANOVA, the impact of coping factors (active and passive) on the Short Form 36 domains was negligible after correction for age, motor function, and depression., Conclusion: Passive coping strategies are the most likely coping response of those with depressive symptoms, whereas active coping strategies are the most likely coping response to influence physical function. Although coping is associated with pain rating, the extent that pain coping responses can impact on QoL seems to be low., Competing Interests: The authors declare no conflict of interest.

Background: More than 50% of patients with infective endocarditis (IE) develop an indication for surgery. Despite its benefit, surgery is associated with a high incidence of multiple organ dysfunction syndrome (MODS) and mortality, which may be linked to increased release of inflammatory mediators during cardiopulmonary bypass (CPB). We therefore assessed plasma cytokine profiles in patients undergoing valve surgery with or without IE., Methods: We performed a prospective case-control pilot study comparing patients undergoing cardiac valve surgery with or without IE. Plasma profiles of inflammatory mediators were measured at 7 defined time points and reported as median (interquartile). The degree of MODS was measured using sequential organ failure assessment (SOFA) score., Results: Between May and December 2016 we included 40 patients (20 in each group). Both groups showed similar distribution of age and gender. Patients with IE had higher preoperative SOFA (6.9± 2.6 vs 3.8 ± 1.1, p<0.001) and operative risk scores (EuroSCORE II 18.6±17.4 vs. 1.8±1.3, p<0.001). In-hospital mortality was higher in IE patients (35% vs. 5%; p<0.001). Multiple organ failure was the cause of death in all non-survivors. At the end of CPB, median levels of following inflammatory mediators were higher in IE compared to control group: IL-6 (119.73 (226.49) vs. 24.48 (40.09) pg/ml, p = 0.001); IL-18 (104.82 (105.99) vs. 57.30 (49.53) pg/ml, p<0.001); Mid-regional pro-adrenomedullin (MR-proADM) (2.06 (1.58) vs. 1.11 (0.53) nmol/L, p = 0.003); MR- pro-atrial natriuretic peptide (MR-proANP) (479.49 (224.74) vs. 266.55 (308.26) pmol/l, p = 0.028). IL-1β and TNF- α were only detectable in IE patients and first after starting CPB. Plasma levels of IL-6, IL-18, MRproADM, and MRproANP during CPB were significantly lower in survivors than in those who died., Conclusion: The presence of infective endocarditis during cardiac valve surgery is associated with increased inflammatory response as evident by higher plasma cytokine levels and other inflammatory mediators. Actively reducing inflammatory response appears to be a plausible therapeutic concept., Trial Registration: ClinicalTrials.gov, ID: NCT02727413., Competing Interests: All other authors declare no competing interests

Purpose: To collect data on diagnosis, treatment, patient's management, and quality of life in patient with bilateral vocal fold paralysis (BVFP)., Methods: A retrospective, observational, multicenter registry study was performed. Medical records of 326 adults with permanent BVFP (median age: 61 years; 70% female, 60% after thyroid surgery) generated between 2010 and 2017., Results: Median time between BVFP onset and inclusion was 1.2 years. Median post-treatment follow-up was 2 months (range: 0-42). Surgery was treatment of choice in 61.7% of the cases, with a 2-year revision rate of 32.4%. Prior to inclusion, 40.2% of the patients underwent at least one surgery. For tracheotomized patients, decannulation rate was 33.8%. Non-surgical treatments included voice therapy and botulinum toxin injection. Corticosteroid application was the most frequent treatment for post-treatment complications (18%; 1-month after surgery). Older age was an independent predictor for dyspnea (Hazard ratio [HR] = 1.041; CI = 1.005 to 1.079; p = 0.026) and the need for oxygen treatment (HR = 1.098; CI = 1.009 to 1.196; p = 0.031). Current alcohol consumption (HR = 2.565; CI = 1.232 to 5.342; p = 0.012) and a cancer-related etiology (HR = 4.767; CI = 1.615 to 14.067; p = 0.005) were independent factors of higher revision risk., Conclusions: Surgery for BVFP is currently not standardized but highly variable. Postoperative and BVFP-related complications and revision surgery are frequent. Complications are linked to patients' alcohol drinking habits and BVFP etiology. These results shall be confirmed by the upcoming evaluation of the prospective data of this registry., Competing Interests: A.H.M, G.F.V., M.G. (Graz) and O.G.L. received research funding from MED-EL. M.G. (Cologne) received travel expenses from MED-EL. The other authors report no disclosures. Furthermore, the funding did not alter our adherence to PLOS ONE policies on sharing data and materials.

On vault in artistic gymnastics, a high run-up speed is thought to be important when performing difficult vaults. To test this assumption in a large cohort of elite athletes, we calculated the correlations between the run-up speed, scores, height and length of flight for handspring-, Tsukahara- and Yurchenko-style vaults and compared the performances of male and female elite and junior athletes (n = 407) during the 2016 European Championships. In females, run-up speed correlated significantly with the difficulty (D-) score and height of flight for all vaulting styles (r ≤ 0.80). In males, run-up speed correlated significantly with the D-score, height and length of flight of Tsukahara (r ≤ 0.69) and Yurchenko vaults only (r ≤ 0.65). Males reached 8-9% higher run-up speeds performing handspring and Tsukahara vaults than did females, but similar run-up speeds performing Yurchenko vaults. Elite females achieved higher run-up speeds than junior females performing Yurchenko vaults. Elite males displayed higher run-up speeds than junior males performing handspring and Tsukahara vaults. We conclude that, in females, more difficult vaults require higher run-up speeds than vaults with lower D-scores and thus, within the measured range of speeds, the faster the run-up, the better, regardless of vaulting style. Males, on the other hand, may not need to exhaust their sprinting capacity, even for the most difficult vaults. Finally, the knowledge of the required run-up speed for each vault helps coaches to estimate each athlete's potential and/or to focus the training on developing the required physical qualities., Competing Interests: The authors have declared that no competing interests exist.

While the cerebral autoregulation sufficiently protects subcortical brain regions during hypoxia or asphyxia, the cerebral cortex is not as adequately protected, which suggests that regulation of the cerebral blood flow (CBF) is area-specific. Hypoxia was induced by inhalation of 5% oxygen, for reoxygenation 100% oxygen was used. Cortical and subcortical CBF (by laser Doppler flowmetry), blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were constantly monitored. Low dosed urapidil was used for α1A-adrenergic receptor blockade. Western blotting was used to determine adrenergic receptor signalling mediators in brain arterioles. During hypoxia cortical CBF decreased to 72 ± 11% (mean reduction 11 ± 3%, p < 0.001) of baseline, whereas subcortical CBF increased to 168±18% (mean increase 43 ± 5%, p < 0.001). Reoxygenation led to peak CBF of 194 ± 27% in the subcortex, and restored cortical CBF. α1A-Adrenergic blockade led to minor changes in cortical CBF, but massively reduced subcortical CBF during hypoxia and reoxygenation-almost aligning CBF in both brain regions. Correlation analyses revealed that α1A-adrenergic blockade renders all CBF-responses pressure-passive during hypoxia and reoxygenation, and confirmed the necessity of α1A-adrenergic signalling for coupling of CBF-responses to oxygen saturation. Expression levels and activation state of key signalling-mediators of α1-receptors (NOSs, CREB, ERK1/2) did not differ between cortex and subcortex. The dichotomy between subcortical and cortical CBF during hypoxia and reoxygenation critically depends on α1A-adrenergic receptors, but not on differential expression of signalling-mediators: signalling through the α1A-subtype is a prerequisite for cortical/subcortical redistribution of CBF., Competing Interests: The authors have declared that no competing interests exist.

The poorly understood mechanisms of dry season persistence of Anopheles spp. mosquitoes through the dry season in Africa remain a critical gap in our knowledge of Plasmodium disease transmission. While it is thought that adult mosquitoes remain in a dormant state throughout this seven-month dry season, the nature of this state remains unknown and has largely not been recapitulated in laboratory settings. To elucidate possible connections of this state with microbial composition, the whole body microbiomes of adult mosquitoes in the dry and wet seasons in two locations of Mali with varying water availability were compared by sequencing the 16S ribosomal RNA gene. These locations were a village near the Niger River with year-round water sources (N'Gabakoro, "riparian"), and a typical Sahelian area with highly seasonal breeding sites (Thierola Area, "Sahelian"). The 16S bacterial data consisted of 2057 sequence variants in 426 genera across 184 families. From these data, we found several compositional differences that were seasonally and spatially linked. Counter to our initial hypothesis, there were more pronounced seasonal differences in the bacterial microbiome of riparian, rather than Sahelian areas. These seasonal shifts were primarily in Ralstonia, Sphingorhabdus, and Duganella spp. bacteria that are usually soil and water-associated, indicating these changes may be from bacteria acquired in the larval environment, rather than adulthood. In Sahelian dry season mosquitoes, there was a unique intracellular bacteria, Anaplasma, which likely was acquired through non-human blood feeding. Cytochrome B analysis of blood meals showed greater heterogeneity in host choice of An. coluzzii independent of season in the Thierola area compared to N'Gabakoro (77.5% vs. 94.6% human-origin blood meal, respectively), indicating a relaxation of anthropophily. Overall, this exploratory study provides valuable indications of spatial and seasonal differences in bacterial composition which help refine this difficult to study state.

Background & Aims: Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history., Methods: A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status., Results: AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status., Conclusion: As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.

Lithium therapy has been shown to affect imaging measures of brain function and microstructure in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. The aim of this proof-of-concept study was to explore whether changes in brain microstructure also entail changes in functional connectivity. Functional MRI data of seven cognitively impaired HIV infected individuals enrolled in an open-label lithium study were included in the connectivity analysis. Seven regions of interest (ROI) were defined based on previously observed lithium induced microstructural changes measured by Diffusion Tensor Imaging. Generalized partial directed coherence (gPDC), based on time-variant multivariate autoregressive models, was used to quantify the degree of connectivity between the selected ROIs. Statistical analyses using a linear mixed model showed significant differences in the average node strength between pre and post lithium therapy conditions. Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity. Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention. Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.

Starch synthase (SS) and branching enzyme (BE) establish the two glycosidic linkages existing in starch. Both enzymes exist as several isoforms. Enzymes derived from several species were studied extensively both in vivo and in vitro over the last years, however, analyses of a functional interaction of SS and BE isoforms are missing so far. Here, we present data from in vitro studies including both interaction of leaf derived and heterologously expressed SS and BE isoforms. We found that SSI activity in native PAGE without addition of glucans was dependent on at least one of the two BE isoforms active in Arabidopsis leaves. This interaction is most likely not based on a physical association of the enzymes, as demonstrated by immunodetection and native PAGE mobility analysis of SSI, BE2, and BE3. The glucans formed by the action of SSI/BEs were analysed using leaf protein extracts from wild type and be single mutants (Atbe2 and Atbe3 mutant lines) and by different combinations of recombinant proteins. Chain length distribution (CLD) patterns of the formed glucans were irrespective of SSI and BE isoforms origin and still independent of assay conditions. Furthermore, we show that all SS isoforms (SSI-SSIV) were able to interact with BEs and form branched glucans. However, only SSI/BEs generated a polymodal distribution of glucans which was similar to CLD pattern detected in amylopectin of Arabidopsis leaf starch. We discuss the impact of the SSI/BEs interplay for the CLD pattern of amylopectin.

An advanced graph theoretical approach is introduced that enables a higher level of functional interpretation of samples of directed networks with identical fixed pairwise different vertex labels that are drawn from a particular population. Compared to the analysis of single networks, their investigation promises to yield more detailed information about the represented system. Often patterns of directed edges in sample element networks are too intractable for a direct evaluation and interpretation. The new approach addresses the problem of simplifying topological information and characterizes such a sample of networks by finding its locatable characteristic topological patterns. These patterns, essentially sample-specific network motifs with vertex labeling, might represent the essence of the intricate topological information contained in all sample element networks and provides as well a means of differentiating network samples. Central to the accurateness of this approach is the null model and its properties, which is needed to assign significance to topological patterns. As a proof of principle the proposed approach has been applied to the analysis of networks that represent brain connectivity before and during painful stimulation in patients with major depression and in healthy subjects. The accomplished reduction of topological information enables a cautious functional interpretation of the altered neuronal processing of pain in both groups.

This study investigated electroencephalographic correlates in chronically depressed patients compared to healthy controls using intracutaneously applied electrical pain stimulus, to better understand the interaction between pain processing and depression. A close interaction between pain and depression is generally recognized although the precise mechanisms are not yet fully understood. The present study focuses on the hypothesis that effective brain connectivity in major depression patients is altered. Multifunctional interactions between brain regions represent a robust index of effective interactions within the brain, and can be quantified by network redundancy. Thus, structural network differences between 18 normal controls and 18 major depression patients before as well as during the processing of moderately painful intracutaneous electrical stimuli were investigated on the basis of network redundancy differences. In our sample, both patients and control subjects exhibit comparable network redundancies before stimulus application. Caused by the stimulus, there is a global increase of network redundancy in both groups. This increase is diminished in the group of major depression patients. We found clear differences between patients and controls during the stimulus processing, where the network redundancy in normal controls is larger in comparison to patients. The differences might be explained by the fact that major depression patients are more restricted to the affective component of the processing. The well-established biasing to affective processing might suppress the somatosensory processing resulting in a lower number of connections within the considered network. This might then lead to a reduction in network redundancy during stimulus processing.

The Pycnogonida or sea spiders are cryptic, eight-legged arthropods with four median ocelli in a 'periscope' or eye tubercle. In older attempts at reconstructing phylogeny they were Arthropoda incertae sedis, but recent molecular trees placed them as the sister group either to all other euchelicerates or even to all euarthropods. Thus, pycnogonids are among the oldest extant arthropods and hold a key position for the understanding of arthropod evolution. This has stimulated studies of new sets of characters conductive to cladistic analyses, e.g. of the chelifores and of the hox gene expression pattern. In contrast knowledge of the architecture of the visual system is cursory. A few studies have analysed the ocelli and the uncommon "pseudoinverted" retinula cells. Moreover, analyses of visual neuropils are still at the stage of Hanström's early comprehensive works. We have therefore used various techniques to analyse the visual fibre pathways and the structure of their interrelated neuropils in several species. We found that pycnogonid ocelli are innervated to first and second visual neuropils in close vicinity to an unpaired midline neuropil, i.e. possibly the arcuate body, in a way very similar to ancestral euarthropods like Euperipatoides rowelli (Onychophora) and Limulus polyphemus (Xiphosura). This supports the ancestrality of pycnogonids and sheds light on what eyes in the pycnogonid ground plan might have 'looked' like. Recently it was suggested that arthropod eyes originated from simple ocelli similar to larval eyes. Hence, pycnogonid eyes would be one of the early offshoots among the wealth of more sophisticated arthropod eyes.

Background: Vector susceptibility to Plasmodium infection is treated primarily as a vector trait, although it is a composite trait expressing the joint occurrence of the parasite and the vector with genetic contributions of both. A comprehensive approach to assess the specific contribution of genetic and environmental variation on "vector susceptibility" is lacking. Here we developed and implemented a simple scheme to assess the specific contributions of the vector, the parasite, and the environment to "vector susceptibility." To the best of our knowledge this is the first study that employs such an approach., Methodology/principal Findings: We conducted selection experiments on the vector (while holding the parasite "constant") and on the parasite (while holding the vector "constant") to estimate the genetic contributions of the mosquito and the parasite to the susceptibility of Anopheles stephensi to Plasmodium gallinaceum. We separately estimated the realized heritability of (i) susceptibility to parasite infection by the mosquito vector and (ii) parasite compatibility (transmissibility) with the vector while controlling the other. The heritabilities of vector and the parasite were higher for the prevalence, i.e., fraction of infected mosquitoes, than the corresponding heritabilities of parasite load, i.e., the number of oocysts per mosquito., Conclusions: The vector's genetics (heritability) comprised 67% of "vector susceptibility" measured by the prevalence of mosquitoes infected with P. gallinaceum oocysts, whereas the specific contribution of parasite genetics (heritability) to this trait was only 5%. Our parasite source might possess minimal genetic diversity, which could explain its low heritability (and the high value of the vector). Notably, the environment contributed 28%. These estimates are relevant only to the particular system under study, but this experimental design could be useful for other parasite-host systems. The prospects and limitations of the genetic manipulation of vector populations to render the vector resistant to the parasite are better considered on the basis of this framework.

Background: As pathogens that circumvent the host immune response are favoured by selection, so are host alleles that reduce parasite load. Such evolutionary processes leave their signature on the genes involved. Deciphering modes of selection operating on immune genes might reveal the nature of host-pathogen interactions and factors that govern susceptibility in host populations. Such understanding would have important public health implications., Methodology/findings: We analyzed polymorphisms in four mosquito immune genes (SP14D1, GNBP, defensin, and gambicin) to decipher selection effects, presumably mediated by pathogens. Using samples of Anopheles arabiensis, An. quadriannulatus and four An. gambiae populations, as well as published sequences from other Culicidae, we contrasted patterns of polymorphisms between different functional units of the same gene within and between populations. Our results revealed selection signatures operating on different time scales. At the most recent time scale, within-population diversity revealed purifying selection. Between populations and between species variation revealed reduced differentiation (GNBP and gambicin) at coding vs. noncoding- regions, consistent with balancing selection. McDonald-Kreitman tests between An. quadriannulatus and both sibling species revealed higher fixation rate of synonymous than nonsynonymous substitutions (GNBP) in accordance with frequency dependent balancing selection. At the longest time scale (>100 my), PAML analysis using distant Culicid taxa revealed positive selection at one codon in gambicin. Patterns of genetic variation were independent of exposure to human pathogens., Significance and Conclusions: Purifying selection is the most common form of selection operating on immune genes as it was detected on a contemporary time scale on all genes. Selection for "hypervariability" was not detected, but negative balancing selection, detected at a recent evolutionary time scale between sibling species may be rather common. Detection of positive selection at the deepest evolutionary time scale suggests that it occurs infrequently, possibly in association with speciation events. Our results provided no evidence to support the hypothesis that selection was mediated by pathogens that are transmitted to humans.