Introduction: Uremic retention solutes have been alleged to induce the apoptotic program of different cell types, including peripheral blood mononuclear leukocytes (PBL), which may contribute to ...uremic leukopenia and immune dysfunction. Methods: The molecular effects of these solutes were investigated in uremic PBL (u-PBL) and mononuclear cell lines (THP-1 and K562) exposed to the high molecular weight fraction of uremic plasma (u-HMW) prepared by in vitro ultrafiltration with 50 kDa cut-off microconcentrators. Results: u-PBL show reduced cell viability and increased apoptotic death compared to healthy control PBL (c-PBL). u-HMW induce apoptosis both in u-PBL and c-PBL, as well as in mononuclear cell lines, also stimulating cellular H 2 O 2 formation and secretion, IRE1-α-mediated endoplasmic reticulum stress signaling, and JNK/cJun pathway activation. Also, u-HMW induce autophagy in THP-1 monocytes. u-PBL were characterized by the presence in their cellular proteome of the main proteins and carbonylation targets of u-HMW, namely albumin, transferrin, and fibrinogen, and by the increased expression of receptor for advanced glycation end-products, a scavenger receptor with promiscuous ligand binding properties involved in leukocyte activation and endocytosis. Conclusions: Large uremic solutes induce abnormal endocytosis and terminal alteration of cellular proteostasis mechanisms in PBL, including UPR/ER stress response and autophagy, ultimately activating the JNK-mediated apoptotic signaling of these cells. These findings describe the suicidal role of immune cells in facing systemic proteostasis alterations of kidney disease patients, a process that we define as the immuno-proteostasis response of uremia.
On the Internet, information circulates fast and widely, and the form of content adapts to comply with users' cognitive abilities. Memes are an emerging aspect of the internet system of ...signification, and their visual schemes evolve by adapting to a heterogeneous context. A fundamental question is whether they present culturally and temporally transcendent characteristics in their organizing principles. In this work, we study the evolution of 2 million visual memes published on Reddit over ten years, from 2011 to 2020, in terms of their statistical complexity and entropy. A combination of a deep neural network and a clustering algorithm is used to group memes according to the underlying templates. The grouping of memes is the cornerstone to trace the growth curve of these objects. We observe an exponential growth of the number of new created templates with a doubling time of approximately 6 months, and find that long-lasting templates are associated with strong early adoption. Notably, the creation of new memes is accompanied with an increased visual complexity of memes content, in a continuous effort to represent social trends and attitudes, that parallels a trend observed also in painting art.
► Profiling of circulating miRs revealed age-related differences. ► MiR-21 was decreased in centenarians and increased in CVD patients. ► A significant correlation between miR-21 and C-reactive ...protein and fibrinogen was observed. ► MiR-21 appears as circulating biomarker of inflammation in aging process and CVD.
Circulating microRNAs (miRs) have been investigated as diagnostic/prognostic biomarkers in human diseases. However, little is known about their expression throughout the aging process.
Eleven healthy individuals aged 20, 80 and 100years underwent miR plasma profiling. The validation cohort consisted of 111 healthy adults (CTR) aged 20–105years and included 30 centenarians. In addition, 34 patients with cardiovascular disease (CVD) and 15 healthy centenarian offspring (CO) were enrolled.
An exploratory factorial analysis grouped the miRs into three main factors: factor 1 primarily higher in 20-year-old subjects, but these differences did not reach statistical significance, factor 2 primarily higher in octogenarians and factor 3 primarily higher in centenarians. MiR-21, the most highly expressed miR of factors 2 and 3, was further validated, confirming the differences in the age groups. MiR-21 expression was higher in the CVD patients and lower in the CO compared to the age-matched CTR. MiR-21 was correlated with C-reactive protein and fibrinogen levels. TGF-β signaling was the predicted common pathway targeted by miRs of factors 2 and 3. TGF-βR2 mRNA, a validated miR-21 target, showed the highest expression in the leukocytes from a subset of the octogenarians.
Our findings suggest that miR-21 may be a new biomarker of inflammation.
The COVID-19 pandemic has been characterized by a social media "infodemic": an overabundance of information whose authenticity may not always be guaranteed. With the potential to lead individuals to ...harmful decisions for the society, this infodemic represents a severe threat to information security, public health and democracy. In this paper, we assess the interplay between the infodemic and specific aspects of the pandemic, such as the number of cases, the strictness of containment measures, and the news media coverage. We perform a comparative study on three countries that employed different managements of the COVID-19 pandemic in 2020-namely Italy, the United Kingdom, and New Zealand. We first analyze the three countries from an epidemiological perspective to characterize the impact of the pandemic and the strictness of the restrictions adopted. Then, we collect a total of 6 million posts from Facebook to describe user news consumption behaviors with respect to the reliability of such posts. Finally, we quantify the relationship between the number of posts published in each of the three countries and the number of confirmed cases, the strictness of the restrictions adopted, and the online news media coverage about the pandemic. Our results show that posts referring to reliable sources are consistently predominant in the news circulation, and that users engage more with reliable posts rather than with posts referring to questionable sources. Furthermore, our modelling results suggest that factors related to the epidemiological and informational ecosystems can serve as proxies to assess the evolution of the infodemic.
To identify a set of variables that could discriminate patients with adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome from subjects with fever of ...unknown origin (FUO).
We enrolled 74 adults diagnosed with PFAPA syndrome according to the currently used pediatric diagnostic criteria and 62 additional patients with FUO. After having collected clinical and laboratory data from both groups, univariate and multivariate analyses were performed to identify the variables associated with PFAPA diagnosis. Odds ratio (OR) values, their statistical significance, and corresponding 95% confidence interval (CI) were evaluated for each diagnostic factor both at the univariate and multivariate analyses. Diagnostic accuracy was evaluated by the area under receiver operating characteristic (ROC) curve, while the leave-one-out cross-validation procedure was used to ensure that the model maintains the same diagnostic power when applied to new data.
According to the multivariate analysis, the clinical variables that discriminated PFAPA patients were: fever episodes associated with cervical lymphadenitis (OR = 92;
< 0.0001), fever attacks associated with erythematous pharyngitis (OR = 231;
< 0.0001), increased inflammatory markers during fever attacks (OR = 588;
= 0.001), and the lack of clinical and laboratory signs of inflammation between flares (OR = 1202;
< 0.0001). These variables were considered for a diagnostic model which accounted for their OR values. The diagnostic accuracy of the proposed set of criteria corresponded to an area under ROC curve of 0.978 (95% CI 0.958-0.998), with a model sensitivity and specificity equal to 93.4% (95% CI 87.5-96.5%) and 91.7% (95% CI 82.8-96.7%), respectively.
we have provided herein a set of clinical diagnostic criteria for adult-onset PFAPA syndrome. Our criteria represent an easy-to-use diagnostic tool aimed at identifying PFAPA patients among subjects with FUO with a high-predictive potential, as shown by its very high sensitivity and specificity.
Abstract Background Geriatric patients with acute non-ST elevation myocardial infarction (NSTEMI) can frequently present atypical symptoms and non-diagnostic electrocardiogram. The detection of ...modest cardiac troponin T (cTnT) elevation is challenging for physicians needing to routinely triage these patients. Unfortunately, non-coronary diseases, such as acute heart failure (CHF), may cause cTnT elevation. Circulating microRNAs (miRs) have emerged as biomarkers of MI. However, their diagnostic potential needs to be determined in elderly NSTEMI patients. Methods 92 NSTEMI patients (82.6 ± 6.9 years old; complicated by CHF in 74% of cases) and 81 patients with acute CHF without AMI (81.3 ± 6.8 years old) were enrolled at presentation. A third group comprised 99 age-matched healthy control subjects (CTR). Plasma levels of miR-1, -21, -133a, -208a, -423-5p and -499-5p were analyzed. Results MiR-1, -21 -133a and -423-5p showed a 3- to 10-fold increase and miR-499-5p exhibited > 80-fold increase in acute NSTEMI patient vs. CTR. MiR-499-5p and -21 showed a significantly increased expression in NSTEMI vs. CHF. Interestingly, mir-499-5p was comparable to cTnT in discriminating NSTEMI vs. CTR and CHF patients. Its diagnostic accuracy was higher than conventional and hs-cTnT in differentiating NSTEMI (n = 31) vs. acute CHF (n = 32) patients with modest cTnT elevation at presentation (miR-499-5p AUC = 0.86 vs. cTnT AUC = 0.68 and vs. hs-cTnT AUC = 0.70). Conclusions Circulating miR-499-5p is a sensitive biomarker of acute NSTEMI in the elderly, exhibiting a diagnostic accuracy superior to that of cTnT in patients with modest elevation at presentation.
Conspiracy theories proliferate online. We provide an overview of information consumption patterns related to conspiracy content on four mainstream social media platforms (Facebook, Twitter, YouTube, ...and Reddit), with a focus on niche ones. Opinion polarisation and echo chambers appear as pivotal elements of communication around conspiracy theories. A relevant role may also be played by the content moderation policies enforced by each social media platform. Banning contents or users from a social media could lead to a level of user segregation that goes beyond echo chambers and reaches the entire social media space, up to the formation of ‘echo platforms’. The insurgence of echo platforms is a new online phenomenon that needs to be investigated as it could foster many dangerous phenomena that we observe online, including the spreading of conspiracy theories.
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