A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. METHODS: We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. RESULTS: We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. CONCLUSIONS: Our results suggest that the innate immune system is central to SSc disease processes but that subtle distinctions exist between tissues. Our approach provides a framework for examining molecular signatures of disease in fibrosis and autoimmune diseases and for leveraging publicly available data to understand common and tissue-specific disease processes in complex human diseases

Optimization of the Contrast Mixture Ratio for Simultaneous Direct MR and CT Arthrography: an in Vitro Study

OBJECTIVE: This study was designed to determine the optimal mixture ratio of gadolinium and iodinated contrast agent for simultaneous direct MR arthrography and CT arthrography. MATERIALS AND METHODS: An in vitro study was performed utilizing mixtures of gadolinium at six different concentrations (0.625, 1.25, 2.5, 5.0, 10 and 20 mmol/L) and iodinated contrast agent at seven different concentrations (0, 12.5, 25, 37.5, 50, 75 and 92-99.9%). These mixtures were placed in tissue culture plates, and were then imaged with CT and MR (with T1-weighted sequences, proton-density sequences and T2-weighted sequences). CT numbers and signal intensities were measured. Pearson's correlation coefficients were used to assess the correlations between the gadolinium/iodinated contrast agent mixtures and the CT numbers/MR signal intensities. Scatter diagrams were plotted for all gadolinium/iodinated contrast agent combinations and two radiologists in consensus identified the mixtures that yielded the optimal CT numbers and MR signal intensities. RESULTS: The CT numbers showed significant correlation with iodinated contrast concentrations (r = 0.976, p < 0.001), whereas the signal intensities as measured on MR images showed a significant correlation with both gadolinium and iodinated contrast agent concentrations (r = -484 to -0.719, p < 0.001). A review of the CT and MR images, graphs, and scatter diagram of 42 combinations of the contrast agent showed that a concentration of 1.25 mmol/L gadolinium and 25% iodinated contrast agent was the best combination for simultaneous CT and MR imaging. CONCLUSION: A mixture of 1.25 mmol/L gadolinium and 25% iodinated contrast agent was found to be optimal for simultaneous direct MR arthrography and CT arthrography

The study of vancomycin use and its adverse reactions associated to patients of a brazilian university hospital

<p>Abstract</p> <p>Background</p> <p>Vancomycin is an antibiotic of growing importance in the treatment of hospital infections, with particular emphasis on its value in the fight against methicillin-resistant <it>Staphylococcus aureus</it>. However its usage profile must be evaluated to assure maximum benefit and minimum risk.</p> <p>Findings</p> <p>A cross-sectional retrospective study was carried out among inpatients that received vancomycin in a Brazilian quaternary hospital. The occurrence of adverse reactions reported was evaluated in medical records relating to patients taking vancomycin during a one year period. Males comprised 52% (95% CI: 41.7-60.2%) of the sample population, with a mean age of 50.6 (95% CI: 47.2-54.0) years and mean treatment period of 9.7 (95% CI: 8.0-11.5) Days. It was verified that nephrotoxicity occurred in 18.4% (95% CI: 11.3-27.5) of patients, Red man syndrome occurred in 2% (95% CI 0.2-7.2), while the occurrence of thrombocytopenia was 7.1% (95% CI: 2.9-14.2).</p> <p>Conclusions</p> <p>It may be noted that even after 50 years of use, adverse reactions associated with vancomycin continue with high frequency, presenting a public health problem, especially considering its current use in cases of multidrug resistant infections. In this context, we emphasize the importance of intensive pharmacovigilance in hospital as a surveillance tool after drug approval by the sanitary authority.</p

Mindfulness-Based Cognitive Therapy for Mental Health Professionals—a Pilot Study

We investigated the adherence of mental health professionals to a Mindfulness-Based Cognitive Therapy (MBCT) programme as well as the impact of MBCT on mindful awareness and attention, psychological well-being and distress, state and trait anxiety, worry and satisfaction with life. The design comprised of a prospective uncontrolled intervention study with pre- and post-measurements of meditation adherence and measures of psychological well-being. Twenty-seven mental health professionals participated in an 8-week MBCT programme for relapse prevention of depression, modified for healthy individuals. Their homework, mindful awareness and attention (Mindful Awareness and Attention Scale), general psychological well-being (General Health Questionnaire), state and trait anxiety (State-Trait Anxiety Inventory), satisfaction with life (Satisfaction with Life Scale), general psychopathology (Brief Symptom Inventory) as well as worry (Penn State Worry Questionnaire) were measured at week 1 and 8 during the intervention and at week 20 as follow-up. Twenty four of 27 (88 %) mental health professionals completed the course and were included in the analysis. Of these, 75 % (18 of 24) were female with a mean age of 36 years and a mean experience in cognitive behavioural therapy (CBT) of 6 years. Sixty-three per cent (15 of 24) reported continued practice at 20-week follow-up. A statistically significant improvement of mindful awareness and psychological well-being, with significant reduction in worry, trait anxiety and general psychopathology, was observed in participants who continued some form of meditation practice during the follow-up period. The majority of mental health professionals adhered to the MBCT meditation practice, and the more they practised mindfulness meditation, the more they experienced an increase in mindful awareness and attention, general psychological well-being and a decrease in general psychopathology, trait anxiety and worry

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on Radiation Safety

info:eu-repo/semantics/publishedVersio

Analysis of the unexplored features of rrs (16S rDNA) of the Genus Clostridium

<p>Abstract</p> <p>Background</p> <p>Bacterial taxonomy and phylogeny based on <it>rrs </it>(16S rDNA) sequencing is being vigorously pursued. In fact, it has been stated that novel biological findings are driven by comparison and integration of massive data sets. In spite of a large reservoir of <it>rrs </it>sequencing data of 1,237,963 entries, this analysis invariably needs supplementation with other genes. The need is to divide the genetic variability within a taxa or genus at their <it>rrs </it>phylogenetic boundaries and to discover those fundamental features, which will enable the bacteria to naturally fall within them. Within the large bacterial community, <it>Clostridium </it>represents a large genus of around 110 species of significant biotechnological and medical importance. Certain <it>Clostridium </it>strains produce some of the deadliest toxins, which cause heavy economic losses. We have targeted this genus because of its high genetic diversity, which does not allow accurate typing with the available molecular methods.</p> <p>Results</p> <p>Seven hundred sixty five <it>rrs </it>sequences (> 1200 nucleotides, nts) belonging to 110 <it>Clostridium </it>species were analyzed. On the basis of 404 <it>rrs </it>sequences belonging to 15 <it>Clostridium </it>species, we have developed species specific: (i) phylogenetic framework, (ii) signatures (30 nts) and (iii) <it>in silico </it>restriction enzyme (14 Type II REs) digestion patterns. These tools allowed: (i) species level identification of 95 <it>Clostridium </it>sp. which are presently classified up to genus level, (ii) identification of 84 novel <it>Clostridium </it>spp. and (iii) potential reduction in the number of <it>Clostridium </it>species represented by small populations.</p> <p>Conclusions</p> <p>This integrated approach is quite sensitive and can be easily extended as a molecular tool for diagnostic and taxonomic identification of any microbe of importance to food industries and health services. Since rapid and correct identification allows quicker diagnosis and consequently treatment as well, it is likely to lead to reduction in economic losses and mortality rates.</p

Mindfulness-Based Cognitive Therapy for Mental Health Professionals: a Long-Term Quantitative Follow-up Study

The authors investigated whether the psychological benefits and meditation practice identified 3 months after attending a mindfulness-based cognitive therapy (MBCT) programme were maintained in a group of mental health professionals at 18 months follow-up. Of the 23 participants who attended the original MBCT programme, 18 agreed to participate. A repeated measures design was employed with the following measures taken: mindfulness; psychological well-being; life satisfaction; trait worry; trait and state anxiety; and an index of weekly meditation practice. A measure of life events and perceived stress was also included. Participants (N = 10) who provided data at each of the three time points—baseline, 3 months follow-up and 18 months follow-up—were included in the repeated measures ANOVAs. Compared to baseline, a significant improvement in levels of mindfulness, trait anxiety and trait worry was noted at 18 months follow-up. Three quarters of the current sample maintained some form of meditation practice although weekly amounts of meditation practice were found to be unrelated to psychological well-being. Contrary to prediction, life events and related levels of perceived stress correlated positively with levels of mindfulness. Attending a MBCT group as a mental health professional appears to have a positive impact on psychological well-being and ongoing meditation practice which persists long after the end of the intervention. Reasons for a lack of association between length of weekly practice and psychological well-being, as well as the positive relationship between perceived stress and mindfulness, are discussed