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Novel direct oral anticoagulants (DOACs) are prescribed worldwide in the treatment of non-valvular atrial fibrillation. Adverse reactions have been reported following the use of DOACs. One notable trend in the literature is the growing number of reported cases of esophagitis dissecans superficialis (EDS) generated by DOAC use. We hereby report the case of a 73-year-old woman who presented to the hospital with asthenia, dysphagia, and melena two days prior to admission. The patient had taken apixaban due to non-valvular paroxysmal atrial fibrillation for a few weeks. The biological panel showed moderate anemia with a hemoglobin level of 7.7 g/dL Apixaban-induced EDS was diagnosed by the characteristic endoscopic findings. The patient received treatment with a proton pump inhibitor (pantoprazole) in a double dose. Also, an iron treatment was recommended for a period of six months. The follow-up endoscopy at one month confirmed the healing of the esophageal lesions. The case was discussed with the cardiologist. The first anticoagulant treatment proposed after discharge was a vitamin K antagonist (acenocumarol) but the patient refused this medication and thus it was decided to initiate rivaroxaban. Although DOACs have demonstrated their efficacy in the prevention and treatment of stroke and thromboembolism among the aging demographic, cases of DOAC-induced EDS will continue to pose numerous challenges for physicians worldwide.

This study aimed to investigate the effects of antiepileptic drugs on salience network regions in patients with epilepsy with generalized tonic-clonic seizures alone (EGTCSa). A retrospective observational case-control study was performed on 40 patients diagnosed with epilepsy with EGTCSa and 40 healthy age-matched controls. In LORETA, a voxel-by-voxel analysis between regions from the salience network was performed for both hemispheres, specifically between the anterior cingulate (BA 32 and BA 24) and the sublobar insula (BA 13). Subsequently, a Wilcoxon rank-sum test (the Mann-Whitney U test) was conducted for the equality of medians in the transformation matrix. A comparison was then made between each region of interest as defined by the salience network and the controls. Marked differences were found in the brain regions assessed in patients with EGTCSa treated with valproic acid and carbamazepine compared to the control group; few differences in patients treated with levetiracetam; and no difference was found in the group without treatment compared with those in the control group. These results suggest that ASMs can influence cognitive processes, which provide novel insights toward understanding the neural mechanisms underlying the effects of ASMs administration.

In this study, bismuth- and iron-embedded carbon xerogels (XG) were obtained using a modified resorcinol formaldehyde sol–gel synthesis method followed by additional enrichment with iron content. Pyrolysis treatment was performed at elevated temperatures under Ar or N2 atmosphere to obtain nanocomposites with different reduction yields (XGAr or XGN). The interest was focused on investigating the extent to which changes in the pyrolysis atmosphere of these nanocomposites impact the structure, morphology, and electrical properties of the material and consequently affect the electroanalytical performance. The structural and morphological particularities derived from X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) measurements revealed the formation of the nanocomposite phases, mostly metal/oxide components. The achieved performances for the two modified electrodes based on XG treated under Ar or N2 atmosphere clearly differ, as evidenced by the electroanalytical parameters determined from the detection of heavy metal cations (Pb2+) or the use of the square wave voltammetry (SWV) technique, biomarkers (H2O2), or amperometry. By correlating the differences obtained from electroanalytical measurements with those derived from morphological, structural, and surface data, a few utmost important aspects were identified. Pyrolysis under Ar atmosphere favors a significant increase in the α-Fe2O3 amount and H2O2 detection performance (sensitivity of 0.9 A/M and limit of detection of 0.17 μM) in comparison with pyrolysis under N2 (sensitivity of 0.5 A/M and limit of detection of 0.36 μM), while pyrolysis under N2 atmosphere leads to an increase in the metallic Bi amount and Pb2+ detection performance (sensitivity of 8.44 × 103 A/M and limit of detection of 33.05 pM) in comparison with pyrolysis under Ar (sensitivity of 6.47·103 A/M and limit of detection of 46.37 pM).

Background: Recent studies have described unique aspects of default mode network connectivity in patients with idiopathic generalized epilepsy (IGE). A complete background in this field could be gained by combining this research with spectral analysis. Objectives: An important objective of this study was to compare linear connectivity and power spectral densities across different activity bands of patients with juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic–clonic seizures alone (EGTCSA), and drug-resistant IGE (DR-IGE) with healthy, age-matched controls. Methods: This was an observational case–control study. We performed EEG spectral analysis in MATLAB and connectivity analysis with LORETA for 39 patients with IGE and 12 drug-resistant IGE (DR-IGE) and healthy, age-matched subjects. We defined regions of interest (ROIs) from the default mode network (DMN) and performed connectivity statistics using time-varying spectra for paired samples. Using the same EEG data, we compared mean power spectral density (PSD) with epilepsy subgroups and controls across different activity bands. Results: We obtained a modified value for the mean power spectral density in the beta band for the JME group as follows. The connectivity analysis showed that, in general, there was increased linear connectivity in the DMN for the JAE, JME, and EGCTSA groups compared to the healthy controls. Reduced linear connectivity between regions of the DMN was found for DR-IGE. Conclusions: Spectral analysis of electroencephalography (EEG) for generalized epilepsy syndromes seems to be less informative than connectivity analysis for DMN. DMN connectivity analysis, especially for DR-IGE, opens up the possibility of finding biomarkers related to drug response in IGE. [ABSTRACT FROM AUTHOR]

Novel knowledge about the interrelationships and reciprocal effects of migraine and epilepsy, migraine and mood disorders, or migraine and irritable bowel syndrome has emerged in recent decades. Over time, comorbid pathologies associated with migraine that share common physiopathological mechanisms were studied. Among these studied pathologies is epilepsy, a disorder with common ion channel dysfunctions as well as dysfunctions in glutamatergic transmission. A high degree of neuronal excitement and ion channel abnormalities are associated with epilepsy and migraine and antiepileptic drugs are useful in treating both disorders. The coexistence of epilepsy and migraine may occur independently in the same individual or the two may be causally connected. The relationship between cortical spreading depression (CSD) and epileptic foci has been suggested by basic and clinical neuroscience research. The most relevant psychiatric comorbidities associated with migraine are anxiety and mood disorders, which influence its clinical course, treatment response, and clinical outcome. The association between migraine and major depressive disorder can be explained by a robust molecular genetic background. In addition to its role as a potent vasodilator, CGRP is also involved in the transmission of nociception, a phenomenon inevitably linked with the stress and anxiety caused by frequent migraine attacks. Another aspect is the role of gut microbiome in migraine’s pathology and the gut–brain axis involvement. Irritable bowel syndrome patients are more likely to suffer migraines, according to other studies. There is no precise explanation for how the gut microbiota contributes to neurological disorders in general and migraines in particular. This study aims to show that migraines and comorbid conditions, such as epilepsy, microbiota, or mood disorders, can be connected from the bench to the bedside. It is likely that these comorbid migraine conditions with common pathophysiological mechanisms will have a significant impact on best treatment choices and may provide clues for future treatment options.

Inflammatory bowel disease (IBD) comprises two types of chronic intestinal disorders: Crohn’s disease and ulcerative colitis. In long-standing ulcerative colitis disease activity, histological persistent inflammation has been linked to an increased risk of relapse, and long-term corticosteroid use, even when endoscopic remission is reached. In Crohn’s disease, the discontinuous nature of lesions and transmural inflammation have limited the standardized histological assessment. The current evidence from research proposes that besides clinical and endoscopic healing, the achievement of histological healing constitutes an endpoint to assess disease activity and remission in IBD patients concerning better long-term disease outcomes. Histological alterations may persist even in the absence of endoscopic lesions. For these reasons, new advanced techniques promise to revolutionize the field of IBD by improving the endoscopic and histologic assessment, disease characterization, and ultimately patient care, with an established role in daily practice for objective assessment of lesions. This review outlines the importance of including microscopic evaluation in IBD, highlighting the clinical benefits of a deep state of disease remission using validated diagnostic methods and scoring systems for daily clinical practice.

Irritable bowel syndrome (IBS) has a global prevalence of around 4.1% and is associated with a low quality of life and increased healthcare costs. Current guidelines recommend that IBS is diagnosed using the symptom-based Rome IV criteria. Despite this, when patients seek medical attention, they are usually over-investigated. This issue might be resolved by novel technologies in medicine, such as the use of Artificial Intelligence (AI). In this context, this paper aims to review AI applications in IBS. AI in colonoscopy proved to be useful in organic lesion detection and diagnosis and in objectively assessing the quality of the procedure. Only a recently published study talked about the potential of AI-colonoscopy in IBS. AI was also used to study biofilm characteristics in the large bowel and establish a potential relationship with IBS. Moreover, an AI algorithm was developed in order to correlate specific bowel sounds with IBS. In addition to that, AI-based smartphone applications have been developed to facilitate the monitoring of IBS symptoms. From a therapeutic standpoint, an AI system was created to recommend specific diets based on an individual’s microbiota. In conclusion, future IBS diagnosis and treatment may benefit from AI.

Multifunctional materials based on carbon xerogel (CX) with embedded bismuth (Bi) and iron (Fe) nanoparticles are tested for ultrasensitive amperometric detection of lead cation (Pb2+) and hydrogen peroxide (H2O2). The prepared CXBiFe-T nanocomposites were annealed at different pyrolysis temperatures (T, between 600 and 1050 °C) and characterized by X-ray diffraction (XRD), Raman spectroscopy, N2 adsorption, dynamic light scattering (DLS), and electron microscopies (SEM/EDX and TEM). Electrochemical impedance spectroscopy (EIS) and square wave anodic stripping voltammetry (SWV) performed at glassy carbon (GC) electrodes modified with chitosan (Chi)-CXBiFe-T evidenced that GC/Chi-CXBiFe-1050 electrodes exhibit excellent analytical behavior for Pb2+ and H2O2 amperometric detection: high sensitivity for Pb2+ (9.2·105 µA/µM) and outstanding limits of detection (97 fM, signal-to-noise ratio 3) for Pb2+, and remarkable for H2O2 (2.51 µM). The notable improvements were found to be favored by the increase in pyrolysis temperature. Multi-scale parameters such as (i) graphitization, densification of carbon support, and oxide nanoparticle reduction and purification were considered key aspects in the correlation between material properties and electrochemical response, followed by other effects such as (ii) average nanoparticle and Voronoi domain dimensions and (iii) average CXBiFe-T aggregate dimension.

Considering the negative effect of anthropological activities on climate in recent decades, all countries entailed a universal commitment to fight against climate change by boosting innovation and introducing new technologies. In this context, our paper aimed to investigate the impact of innovation input in terms of research and development (R&D) costs and technology expressed as technical equipment and machinery (TEM) on the reported greenhouse gas (GHG) emissions in chemical industry companies in five Central and Eastern European countries. This study employed a panel regression model with fixed effects and covered data from 2015 to 2020. The empirical results emphasize a negative relationship between R&D costs and GHG emissions, indicating the companies’ commitment to developing innovative solutions that contribute to lower destructive emissions. Additionally, the findings related to the influence of TEM on GHG emissions reveal a positive impact, highlighting the need to improve manufacturing technologies. The practical implications of our findings can be meaningful for both policymakers and businesses operating in the chemical industry in developing countries. Policymakers should offer financial incentives to support research and investments in clean technologies, while businesses should prioritise such investments to mitigate GHG emissions.

Abstract In this study we aimed to compare the mineralogical, thermal, physicochemical, and biological characteristics of recent organic carbon-rich sediments (‘sapropels’) from three geographically distant Romanian lakes (Tekirghiol and Amara, SE Romania, and Ursu, Central Romania) with distinct hydrogeochemical origins, presently used for pelotherapy. The investigated lakes were classified as inland brackish Na-Cl-sulfated type (Amara), coastal moderately saline and inland hypersaline Na-Cl types (Tekirghiol and Ursu, respectively). The settled organic matter is largely composed of photosynthetic pigments derived from autochthonous phytoplankton. Kerogen was identified in the sapropel of coastal Tekirghiol Lake suggesting its incipient maturation stage. The mineral composition was fairly similar in all sapropels and mainly consisted of quartz, calcite, and aragonite. Smectite, illite, mixed layer smectite/illite appeared as major clay components. Potentially toxic elements were found in low concentrations. The physical properties (i.e., specific heat, thermal conductivity and retentivity) and cation exchange capacity are comparable to other peloids used for therapy. This study is the first comprehensive multi-approached investigation of the geochemical nature of recent sapropels in Romanian saline lakes and thus contributes to expanding our knowledge on the origin and physicochemical qualities of organic matter-rich peloids with therapeutic uses.

Novel direct oral anticoagulants (DOACs) are prescribed worldwide in the treatment of non-valvular atrial fibrillation. Adverse reactions have been reported following the use of DOACs. One notable trend in the literature is the growing number of reported cases of esophagitis dissecans superficialis (EDS) generated by DOAC use. We hereby report the case of a 73-year-old woman who presented to the hospital with asthenia, dysphagia, and melena two days prior to admission. The patient had taken apixaban due to non-valvular paroxysmal atrial fibrillation for a few weeks. The biological panel showed moderate anemia with a hemoglobin level of 7.7 g/dL Apixaban-induced EDS was diagnosed by the characteristic endoscopic findings. The patient received treatment with a proton pump inhibitor (pantoprazole) in a double dose. Also, an iron treatment was recommended for a period of six months. The follow-up endoscopy at one month confirmed the healing of the esophageal lesions. The case was discussed with the cardiologist. The first anticoagulant treatment proposed after discharge was a vitamin K antagonist (acenocumarol) but the patient refused this medication and thus it was decided to initiate rivaroxaban. Although DOACs have demonstrated their efficacy in the prevention and treatment of stroke and thromboembolism among the aging demographic, cases of DOAC-induced EDS will continue to pose numerous challenges for physicians worldwide. [ABSTRACT FROM AUTHOR]

Abstract Background In vitro models are widely used in nanotoxicology. In these assays, a careful documentation of the fraction of nanomaterials that reaches the cells, i.e. the in vitro delivered dose, is a critical element for the interpretation of the data. The in vitro delivered dose can be measured by quantifying the amount of material in contact with the cells, or can be estimated by applying particokinetic models. For carbon nanotubes (CNTs), the determination of the in vitro delivered dose is not evident because their quantification in biological matrices is difficult, and particokinetic models are not adapted to high aspect ratio materials. Here, we applied a rapid and direct approach, based on femtosecond pulsed laser microscopy (FPLM), to assess the in vitro delivered dose of multi-walled CNTs (MWCNTs). Methods and results We incubated mouse lung fibroblasts (MLg) and differentiated human monocytic cells (THP-1) in 96-well plates for 24 h with a set of different MWCNTs. The cytotoxic response to the MWCNTs was evaluated using the WST-1 assay in both cell lines, and the pro-inflammatory response was determined by measuring the release of IL-1β by THP-1 cells. Contrasting cell responses were observed across the MWCNTs. The sedimentation rate of the different MWCNTs was assessed by monitoring turbidity decay with time in cell culture medium. These turbidity measurements revealed some differences among the MWCNT samples which, however, did not parallel the contrasting cell responses. FPLM measurements in cell culture wells revealed that the in vitro delivered MWCNT dose did not parallel sedimentation data, and suggested that cultured cells contributed to set up the delivered dose. The FPLM data allowed, for each MWCNT sample, an adjustment of the measured cytotoxicity and IL-1β responses to the delivered doses. This adjusted in vitro activity led to another toxicity ranking of the MWCNT samples as compared to the unadjusted activities. In macrophages, this adjusted ranking was consistent with existing knowledge on the impact of surface MWCNT functionalization on cytotoxicity, and might better reflect the intrinsic activity of the MWCNT samples. Conclusion The present study further highlights the need to estimate the in vitro delivered dose in cell culture experiments with nanomaterials. The FPLM measurement of the in vitro delivered dose of MWCNTs can enrich experimental results, and may refine our understanding of their interactions with cells.

Globally, metabolic diseases such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease pose a major public health threat. Many studies have confirmed the causal relationship between risk factors and the etiopathogenesis of these diseases. Despite this, traditional therapeutic management methods such as physical education and diet have proven insufficient. Recently, researchers have focused on other potential pathways for explaining the pathophysiological variability of metabolic diseases, such as the involvement of the intestinal microbiota. An understanding of the relationship between the microbiome and metabolic diseases is a first step towards developing future therapeutic strategies. Currently, much attention is given to the use of biotics family members such as prebiotics (lactolose, soy oligosaccharides, galactooligosaccharides, xylooligosaccharides or inulin) and probiotics (genera Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus or Enterococcus). They can be used both separately and together as synbiotics. Due to their direct influence on the composition of the intestinal microbiota, they have shown favorable results in the evolution of metabolic diseases. The expansion of the research area in the biotics family has led to the discovery of new members, like postbiotics. In the age of personalized medicine, their use as therapeutic options is of great interest to our study.

Abstract Background Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000). Methods MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs. Results At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy. Conclusions These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

Silica submicronic particles doped with Dy and Gd paramagnetic ions were successfully synthesized by using chemical synthesis based on the modified Stöber method, having potential applications as contrast agents for magnetic resonance imaging (MRI).Structural characterization analyses show an amorphous character of the particles (XRD), good thermal stability (DTA), and spheroid shape (SEM). The integration of paramagnetic ions into the silica network was demonstrated by the TEM, EPR and FTIR spectroscopies.The magnetic resonance (MR) relaxivity examinations of the samples show a high rate of relaxivity for the particles doped with Dy, making them suitable as T2 contrast agent for magnetic resonance imaging. This is in contrast to the results obtained on the particles doped with Gd, which are an effective T1-weighted MRI contrast agent. Notably, if the silica structure incorporates both Gd and Dy the particles are suitable for contrast enhancement in both T1 and T2 weighted images. These characteristics of the samples are also supported by the value of the relaxivity ratio (r2/r1) for the three samples doped with paramagnetic ions. The results confirm the sustainability of MRI contrast agent applications for all three synthesized samples.

This study aimed to investigate the effects of antiepileptic drugs on salience network regions in patients with epilepsy with generalized tonic-clonic seizures alone (EGTCSa). A retrospective observational case-control study was performed on 40 patients diagnosed with epilepsy with EGTCSa and 40 healthy age-matched controls. In LORETA, a voxel-by-voxel analysis between regions from the salience network was performed for both hemispheres, specifically between the anterior cingulate (BA 32 and BA 24) and the sublobar insula (BA 13). Subsequently, a Wilcoxon rank-sum test (the Mann-Whitney U test) was conducted for the equality of medians in the transformation matrix. A comparison was then made between each region of interest as defined by the salience network and the controls. Marked differences were found in the brain regions assessed in patients with EGTCSa treated with valproic acid and carbamazepine compared to the control group; few differences in patients treated with levetiracetam; and no difference was found in the group without treatment compared with those in the control group. These results suggest that ASMs can influence cognitive processes, which provide novel insights toward understanding the neural mechanisms underlying the effects of ASMs administration. [ABSTRACT FROM AUTHOR]