Ustekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ...ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers.
We recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-β1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC.
In this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.
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•Fe78Al22 and Fe71Al22Ti7 alloys are prepared by arc melting.•Structural, macroscopic and microscopic magnetic properties are studied.•Coarse-grained structure is obtained in the ...Fe-Al sample.•Fine Fe2TiAl cuboids in Fe-Al(Ti) matrix are seen in the Fe-Al-Ti sample.
The influence of Ti substituting partially Fe in Fe – 22 at.% Al alloy on the structure and magnetic properties is investigated experimentally by electron microscopy, X-ray diffraction, Mössbauer spectrometry, and by magnetic measurements at room and low temperatures. The samples in a form of discs prepared by cutting the arc-melted button-type ingots have yielded a coarse-grained structure in the Fe – 22 at.% Al sample and fine Fe-Al-Ti cuboids embedded in Fe-Al(Ti) matrix in the Fe – 22 at.% Al – 7at.% Ti alloy. The mean cuboids’ size was 45 nm and the mean composition was determined to be close to Fe2TiAl. The as-prepared Fe-Al-Ti samples exhibited substantially reduced saturation magnetization and markedly higher remanent magnetization and coercivity as compared to the as-prepared Fe-Al sample. The thermal treatment of the Fe-Al sample at 1073 K/168 h has changed its magnetic behaviour only slightly, whereas the treatment of the Fe-Al-Ti sample at 1273 K/168 h resulted in remarkable softening of its magnetic properties.
Objective
The burnout syndrome represents a defence mechanism against stress and includes stages with decreased ability to experience feelings and emotional states. This finding suggests that burnout ...might be closely linked to emotional ‘blindness’ as a defence mechanism against negative and overwhelming emotions known as alexithymia. The aim of this study is to examine the relationships between burnout syndrome, alexithymia, depression and traumatic stress symptoms in healthcare professionals.
Methods
This empirical study assessed female healthcare professionals who work with a population of patients with diabetes, utilizing the Maslach Burnout Inventory (MBI-HSSMP), Burnout Measure (BM), Toronto Alexithymia Scale (TAS-20), Beck Depression Inventory (BDI-II) and Traumatic Stress Checklist (TSC-40). Data were analysed using Spearman’s correlation coefficient.
Results
A total of 114 female participants were included (age range, 31–60 years; mean age, 46.62 ± 8.71 years). Statistically significant associations were found between burnout syndrome (BM scores) and alexithymia (TAS-20) (r = 0.41), and between BM scores and traumatic stress (TSC-40; r = 0.63). The MBI-HSSMP emotional exhaustion subscale also correlated with alexithymia (TAS-20) (r = 0.37).
Conclusion
Findings of this study suggest that alexithymia and traumatic stress are related to burnout symptoms. This dynamic may be potentially useful for detecting and preventing burnout syndrome.
Psoriatic patients have altered microbiota, both in the intestine and on the skin. It is not clear, however, whether this is a cause or consequence of the disease. In this study, using an ...experimental mouse model of psoriasis induced by imiquimod (IMQ), we show that oral treatment with a broad spectrum of antibiotics (MIX) or metronidazole (MET) alone mitigates the severity of skin inflammation through downregulation of Th17 immune response in conventional mice. Since some antibiotics, including MET, can influence immune system reactivity, we also evaluated the effect of MIX in the same model under germ-free (GF) conditions. GF mice treated with MET did not show milder signs of imiquimod-induced skin inflammation (IISI) which supports the conclusion that the therapeutic effect is mediated by changes in microbiota composition. Moreover, compared to controls, mice treated with MIX had a significantly higher abundance of the genus
in the intestine and on the skin. Mice treated with MET had a significantly higher abundance of the genera
and
both on the skin and in the intestine and of
in the intestine. Additionally, GF mice and mice monocolonized with either
or segmented filamentous bacteria (SFB) were more resistant to IISI than conventional mice. Interestingly, compared to GF mice, IMQ induced a higher degree of systemic Th17 activation in mice monocolonized with SFB but not with
. The present findings provide evidence that intestinal and skin microbiota directly regulates IISI and emphasizes the importance of microbiota in the pathogenesis of psoriasis.
•Mn2FeSi ribbons prepared by rapid solidification and annealed for 100 h at 773 K.•Two phases with main Heusler phase detected for as-prepared and annealed ribbons.•Single vacancies are the main ...defects in both as-prepared and annealed ribbons.•Antiferromagnetic behavior observed below 45 K in both samples.•Marked magnetic transition at 70 K observed for annealed ribbons.
The structure and magnetic properties of Mn2FeSi alloy as a prospective Heusler material are studied from the viewpoint of the rapid solidification technology used for its preparation. The planar flow casting leads due to fast cooling of the melted material to formation of ribbons with different structural and physical properties. In present study, the crystalline ribbon-type samples are produced and subjected to detail analysis using electron microscopy, positron annihilation spectroscopy, X-ray diffraction, as well as magnetic and Mössbauer measurements. It is shown that the as-prepared Mn2FeSi ribbon is paramagnetic at room temperature and adopts a cubic structure with lattice parameter of 0.567 nm and Néel temperature of antiferromagnetic/paramagnetic transition around 45 K. The presence of other phase(s) observed at low temperatures is reflected also in changes of the structural and physical properties after sample annealing at 773 K for 100 h. The results of microstructure, magnetic, and phase composition observations are completed by the positron life time measurements suggesting single vacancies as the main defects in which the positrons are trapped.
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Ribavirin is a broad-spectrum nucleoside-derived antiviral drug used in combination pharmacotherapy treatment of hepatitis C virus infection. Current evidence indicates that ...ribavirin-associated teratogenicity is not significant in humans, but more information about the developmental toxicity and mechanisms involved in ribavirin placental kinetics is required to assure its safe use in pregnancy. Thus, we have investigated potential roles of equilibrative nucleoside transporters (ENTs, SLC29A), Na+-dependent influx-mediating concentrative nucleoside transporters (CNTs, SLC28A), and ATP-binding cassette (ABC) efflux pumps, in ribavirin placental pharmacokinetics. Our data indicate that ENT1 participates in uptake of ribavirin by BeWo cells, fresh human placental villous fragments and microvillous plasma membrane (MVM) vesicles while activity of CNTs (probably CNT2) was only observed in BeWo cells. In situ dual perfusion experiments with rat term placenta in an open circuit setup showed that ENT inhibition significantly decreases total ribavirin maternal-to-foetal and foetal-to-maternal clearances. In contrast, no contribution of ABC transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), or multidrug resistance-associated protein (ABCC2) was detected in assays with MDCKII cells overexpressing them, or in closed circuit dual perfusion experiments with rat term placenta. In summary, our data show that ribavirin placental pharmacokinetics are largely controlled by ENT1 activity and independent of ABCB1, ABCG2, and ABCC2 efflux pumps.
Transient receptor potential melastatin (TRPM) channels, a subfamily of the TRP superfamily, constitute a diverse group of ion channels involved in mediating crucial cellular processes like calcium ...homeostasis. These channels exhibit complex regulation, and one of the key regulatory mechanisms involves their interaction with calmodulin (CaM), a cytosol ubiquitous calcium-binding protein. The association between TRPM channels and CaM relies on the presence of specific CaM-binding domains in the channel structure. Upon CaM binding, the channel undergoes direct and/or allosteric structural changes and triggers down- or up-stream signaling pathways. According to current knowledge, ion channel members TRPM2, TRPM3, TRPM4, and TRPM6 are directly modulated by CaM, resulting in their activation or inhibition. This review specifically focuses on the interplay between TRPM channels and CaM and summarizes the current known effects of CaM interactions and modulations on TRPM channels in cellular physiology.
The composition of microbiota and the gut-brain axis is increasingly considered a factor in the development of various pathological conditions. The etiology of multiple sclerosis (MS), a chronic ...autoimmune disease affecting the CNS, is complex and interactions within the gut-brain axis may be relevant in the development and the course of MS. In this article, we focus on the relationship between gut microbiota and the pathophysiology of MS. We review the contribution of germ-free mouse studies to our understanding of MS pathology and its implications for treatment strategies to modulate the microbiome in MS. This summary highlights the need for a better understanding of the role of the microbiota in patients' responses to disease-modifying drugs in MS and disease activity overall.
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