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[Effectiveness of Biofeedback for Primary Headache - A Randomized Controlled Study].

Biofeedback-treatment for primary headache is highly recommended. Its expenses are mostly not or not completely covered by health funds, hindering the implementation in the care system. This randomized controlled study aimed at evaluating the efficacy of a biofeedback-treatment for primary headache in the outpatient care system all over Germany.

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Self-Reported Changes in Cognition, Communication and Swallowing in Multiple Sclerosis: Data from the Swedish Multiple Sclerosis Registry and from a National Survey.

The aim of this study was to investigate self-reported cognition, speech, communication and swallowing changes in a large sample of individuals with multiple sclerosis (MS) in Sweden. A second aim was to update information about speech and language pathology (SLP) services received by people with MS (pwMS).

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Impact of Clustering Oral Symptoms in the Pathogenesis of Radiation Caries: A Systematic Review.

Radiation-related caries (RRC) is a disease with a high potential for destruction of the dentition, which impairs quality of life in head-and-neck (HN) cancer (HNC) patients who undergo radiotherapy. In light of the recently described "clustering of oral symptoms theory," the present systematic review (PROSPERO CRD42019132709) aims to assess HN and gastrointestinal (GI) symptom clusters among HNC patients and discusses how these indirect effects of cancer therapy play a pivotal role in the pathophysiology of RRC. The search was performed at PubMed, Scopus, and Embase and resulted in 11 studies that met the inclusion criteria. Data extraction was performed with respect to the presence of HN/GI symptom clusters among HNC patients. The methodological data of the studies included were assessed using the MAStARI and GRADE instruments. The most prevalent reported HN symptoms were dysphagia, xerostomia, and pain. Taste alterations and fatigue were also commonly reported by the patients. Loss of appetite and weight loss were regularly reported in the studies, as well as nausea and vomiting. The results of the present study suggest that HNC treatment generates clusters of oral symptoms, leading to dietary changes, impaired oral hygiene, enamel fragility, and a highly cariogenic oral environment, which may impact the risk for RRC. A better understanding of oral symptom clustering could be of considerable clinical significance for the oral health and quality of life of HNC patients. Therefore, contemporary protocols of RRC prevention must take this broader treatment scenario of symptom clusters such as oral side effects into account.

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Study of the intestinal uptake and permeability of gold nanoparticles using both in vitro and in vivo approaches.

Gold nanoparticles (AuNPs) are highly attractive to biomedical applications. Here, we investigated the effects of (i) ca. 15 nm spherical AuNPs capped with citrate or 11-mercaptoundecanoic acid (MUA), and (ii) ca. 60 nm spherical citrate-capped AuNPs, and ca. 60 nm MUA-capped star-shaped AuNPs on the cytotoxicity, cellular uptake and permeability, using media supplemented or not with 1% fetal bovine serum (FBS) on caucasian colon adenocarcinoma Caco-2 cells. In addition, the colloidal stability of the nanoparticles in media (supplemented or not) was assessed after 24 h-incubations at 60 µM. The 60 nm gold nanospheres and stars were administrated orally to Wistar rats in order to evaluate their systemic absorption and biodistribution after 24h. At non-supplemented media settings, citrate-capped gold nanoparticles seem to be more toxic than their MUA-capped counterparts. Also, smaller nanoparticles show higher toxicity than larger ones. The use of cell culture media with 1% FBS not only increased the stability of all AuNPs, as also significantly reduced their cytotoxicity. In the uptake studies, higher AuNPs incorporation was noticed in serum supplemented media, this effect being particularly significant for the 60 nm nanoparticles. Cellular incorporation depended also on the capping agent and size. None of the tested samples crossed the in vitro intestinal barrier. Confirming the in vitro results, the in vivo biodistribution study of the 60 nm AuNPs orally given to rats showed that their systemic absorption is low and that they are mainly eliminated through the faeces. Altogether, these preliminary results suggest that our novel AuNPs have high potential to be considered promising candidates for application in diagnostics or drug delivery at the intestinal level, showing high biocompatibility. However, unless it is desired that these nanomaterials avoid systemic absorption upon oral administration, additional functionalization should be sought to increase their low bioavailability.

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Associations between air pollution and pediatric eczema, rhinoconjunctivitis and asthma: A meta-analysis of European birth cohorts.

Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades.

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EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas.

Loss of CD58 is a common mechanism for tumor immune evasion in lymphoid malignancies. CD58 loss is known to occur due to both genetic and non-genetic causes; therefore, we hypothesized that restoring CD58 expression in lymphoma cells may be an effective treatment approach. To explore the potential for restoring CD58 expression, we first screened 11 B-cell lymphoma lines and found that 3 had decreased CD58 expression. Among these, CD58 was genetically damaged in two lines but not in the third line. Using the cell line with downregulated CD58 without a genetic abnormality, we performed epigenetic library screening and found that two EZH2 inhibitors, EPZ6438 and GSK126, specifically enhanced CD58 expression. By examining the effect of three EZH2 inhibitors with different selectivity profiles in different B-cell lines, EZH2 inhibition was shown to have a common activity in upregulating CD58 expression. Restoring the expression of CD58 in lymphoma cells using an EZH2 inhibitor was shown to enhance interferon-γ production of T and NK cells against lymphoma cells. H3K27 was shown to be highly trimethylated in the CD58 promoter region, and EZH2 inhibition induced its demethylation and activated transcription of the CD58 gene. These results indicated that EZH2 is involved in the epigenetic silencing of CD58 in lymphoma cells as a mechanism for tumor immune escape, and EZH2 inhibitors are able to restore epigenetically suppressed CD58 expression. Our findings provide a molecular basis for the combination of an EZH2 inhibitor and immunotherapy for lymphoma treatment.

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Cadmium distribution in mature durum wheat grains using dissection, laser ablation-ICP-MS and synchrotron techniques.

Understanding how essential and toxic elements are distributed in cereal grains is a key to improving the nutritional quality of cereal-based products. The main objective of this work was to characterize the distribution of Cd and of nutrients (notably Cu, Fe, Mn, P, S and Zn) in the durum wheat grain. Laser ablation inductively coupled mass spectrometry and synchrotron micro X-ray fluorescence were used for micro-scale mapping of Cd and nutrients. A dissection approach was used to quantitatively assess the distribution of Cd and nutrients among grain tissues. Micro X-ray absorption near-edge spectroscopy was used to identify the Cd chemical environment in the crease. Cadmium distribution was characterized by strong accumulation in the crease and by non-negligible dissemination in the endosperm. Inside the crease, Cd accumulated most in the pigment strand where it was mainly associated with sulfur ligands. High-resolution maps highlighted very specific accumulation areas of some nutrients in the germ, for instance Mo in the root cortex primordia and Cu in the scutellum. Cadmium loading into the grain appears to be highly restricted. In the grain, Cd co-localized with several nutrients, notably Mn and Zn, which challenges the idea of selectively removing Cd-enriched fractions by dedicated milling process.

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Oxadiazolylthiazoles as novel and selective antifungal agents.

Studying the structure-activity relationships (SAR) of oxadiazolylthiazole antibiotics unexpectedly led us to identify ethylenediamine- and propylenediamine-analogs as potential antimycotic novel lead structures. Replacement of the ethylenediamine moiety for the lead compound 7 with cis-diaminocyclohexyl group (compound 18) significantly enhanced the antifungal activity. In addition to the high safety margin of 18 against mammalian cells, it showed highly selective broad-spectrum activity against fungal cells without inhibiting the human normal microbiota. The antifungal activity of 18 was investigated against 20 drug-resistant clinically important fungi, including Candida species, Cryptococcus, and Aspergillus fumigatus strains. In addition to the low MIC values that mostly ranged between 0.125 and 2.0 μg/mL, compound 18 outperformed fluconazole in disrupting mature Candida biofilm.

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People represent mental states in terms of rationality, social impact, and valence: Validating the 3d Mind Model.

Humans can experience a wide variety of different thoughts and feelings in the course of everyday life. To successfully navigate the social world, people need to perceive, understand, and predict others' mental states. Previous research suggests that people use three dimensions to represent mental states: rationality, social impact, and valence. This 3d Mind Model allows people to efficiently "see" the state of another person's mind by considering whether that state is rational or emotional, more or less socially impactful, and positive or negative. In the current investigation, we validate this model using neural, behavioral, and linguistic evidence. First, we examine the robustness of the 3d Mind Model by conducting a mega-analysis of four fMRI studies in which participants considered others' mental states. We find evidence that rationality, social impact, and valence each contribute to explaining the neural representation of mental states. Second, we test whether the 3d Mind Model offers the optimal combination of dimensions for describing neural representations of mental state. Results reveal that the 3d Mind Model achieve the best performance among a large set of candidate dimensions. Indeed, it offers a highly explanatory account of mental state representation, explaining over 80% of reliable neural variance. Finally, we demonstrate that all three dimensions of the model likewise capture convergent behavioral and linguistic measures of mental state representation. Together, these findings provide strong support for the 3d Mind Model, indicating that is it is a robust and generalizable account of how people think about mental states.

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Functional characterization of NLRX1 in rabbit during enterohemorrhagic Escherichia coli infection.

Nucleotide oligomerization domain (NOD) like receptor X1 (NLRX1) is a member of pattern recognition receptor, which has been linked to viral response, cancer, and inflammatory diseases. In this study, rabbit NLRX1 (rNLRX1) was firstly cloned from RK-13 cells, which protein contained a NACHT domain and seven LRRs. rNLRX1 was widely expressed in tissues of rabbits, and highly increased in liver, spleen, kidney, and colon after infected with enterohemorrhagic Escherichia coli (EHEC). Overexpression of rNLRX1 negatively regulated NF-κB signaling, and impaired the expression of pro-inflammatory cytokines and defensins. Moreover, deficient of rNLRX1 in RK-13 cells was performed to investigate the possible roles of rNLRX1. Upon EHEC stimulation, knockdown of rNLRX1 markedly enhanced NF-κB activation and downstream responsive cytokines (IL1β and TNFα) and β-defensins (DEFB114, DEFB124, and DEFB125). Furthermore, overexpression of rNLRX1 promoted the proliferation of EHEC, whereas knockdown of rNLRX1 inhibited its growth. Our study identified that rNLRX1 acts as a negative regulatory in anti-microbial responses after EHEC infection.

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