The ideal tricuspid valve annuloplasty (TVA) prosthesis is controversial. This study aimed to compare the effect of rigid versus flexible TVA prostheses on long-term outcomes after repair of ...functional tricuspid regurgitation (FTR).
We included 713 patients who had repair of FTR from 2009 to 2017. Patients were divided into 2 groups according to the type of TVA prosthesis. Group 1 (n = 104) included patients who had repair using rigid rings; group 2 (n = 609) included patients with flexible bands. Median age was 53.5 years (25th through 75th percentiles; range, 42.5-62 years) in group 1 versus 56 years (range, 45-65 years) in group 2 (P = .11). Propensity score matching identified 91 matched pairs for comparison.
In the matched pairs, operative mortality was identical (4 in both groups 4.4%; P ˃ .99). Median follow-up was 55 months (range, 28-83 months). The cumulative incidence of moderate or higher tricuspid regurgitation (TR) in the presence of death as a competing risk was higher in group 2 (subdistribution hazard ratio = 1.63, P = .019; and subdistribution hazard ratio = 1.6, P = .099 before and after matching, respectively). There was a trend of higher pacemaker insertion in group 1 (7 7.69% versus 3 3.3%; P = .34), which did not reach statistical significance after matching. There was no significant change in the degree of TR over time between groups (odds ratio = 1.21, P = .53; and odds ratio = 1.75, P = .21 before and after matching, respectively).
Both types of TVA prostheses had comparable efficacy in managing FTR; however, freedom from moderate or more TR was higher in the rigid ring group.
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Happiness and other emotions spread between people in direct contact, but it is unclear whether massive online social networks also contribute to this spread. Here, we elaborate a novel method for ...measuring the contagion of emotional expression. With data from millions of Facebook users, we show that rainfall directly influences the emotional content of their status messages, and it also affects the status messages of friends in other cities who are not experiencing rainfall. For every one person affected directly, rainfall alters the emotional expression of about one to two other people, suggesting that online social networks may magnify the intensity of global emotional synchrony.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human behaviour is thought to spread through face-to-face social networks, but it is difficult to identify social influence effects in observational studies, and it is unknown whether online social ...networks operate in the same way. Here we report results from a randomized controlled trial of political mobilization messages delivered to 61 million Facebook users during the 2010 US congressional elections. The results show that the messages directly influenced political self-expression, information seeking and real-world voting behaviour of millions of people. Furthermore, the messages not only influenced the users who received them but also the users' friends, and friends of friends. The effect of social transmission on real-world voting was greater than the direct effect of the messages themselves, and nearly all the transmission occurred between 'close friends' who were more likely to have a face-to-face relationship. These results suggest that strong ties are instrumental for spreading both online and real-world behaviour in human social networks.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Emotional states can be transferred to others via emotional contagion, leading people to experience the same emotions without their awareness. Emotional contagion is well established in laboratory ...experiments, with people transferring positive and negative emotions to others. Data from a large real-world social network, collected over a 20-y period suggests that longer-lasting moods (e.g., depression, happiness) can be transferred through networks Fowler JH, Christakis NA (2008) BMJ 337:a2338, although the results are controversial. In an experiment with people who use Facebook, we test whether emotional contagion occurs outside of in-person interaction between individuals by reducing the amount of emotional content in the News Feed. When positive expressions were reduced, people produced fewer positive posts and more negative posts; when negative expressions were reduced, the opposite pattern occurred. These results indicate that emotions expressed by others on Facebook influence our own emotions, constituting experimental evidence for massive-scale contagion via social networks. This work also suggests that, in contrast to prevailing assumptions, in-person interaction and nonverbal cues are not strictly necessary for emotional contagion, and that the observation of others’ positive experiences constitutes a positive experience for people.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Protein aggregates and damaged organelles are tagged with ubiquitin chains to trigger selective autophagy. To initiate mitophagy, the ubiquitin kinase PINK1 phosphorylates ubiquitin to activate the ...ubiquitin ligase parkin, which builds ubiquitin chains on mitochondrial outer membrane proteins, where they act to recruit autophagy receptors. Using genome editing to knockout five autophagy receptors in HeLa cells, here we show that two receptors previously linked to xenophagy, NDP52 and optineurin, are the primary receptors for PINK1- and parkin-mediated mitophagy. PINK1 recruits NDP52 and optineurin, but not p62, to mitochondria to activate mitophagy directly, independently of parkin. Once recruited to mitochondria, NDP52 and optineurin recruit the autophagy factors ULK1, DFCP1 and WIPI1 to focal spots proximal to mitochondria, revealing a function for these autophagy receptors upstream of LC3. This supports a new model in which PINK1-generated phospho-ubiquitin serves as the autophagy signal on mitochondria, and parkin then acts to amplify this signal. This work also suggests direct and broader roles for ubiquitin phosphorylation in other autophagy pathways.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PINK1 kinase activates the E3 ubiquitin ligase Parkin to induce selective autophagy of damaged mitochondria. However, it has been unclear how PINK1 activates and recruits Parkin to mitochondria. ...Although PINK1 phosphorylates Parkin, other PINK1 substrates appear to activate Parkin, as the mutation of all serine and threonine residues conserved between Drosophila and human, including Parkin S65, did not wholly impair Parkin translocation to mitochondria. Using mass spectrometry, we discovered that endogenous PINK1 phosphorylated ubiquitin at serine 65, homologous to the site phosphorylated by PINK1 in Parkin's ubiquitin-like domain. Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. In cells, the phosphomimetic ubiquitin mutant S65D bound and activated Parkin. Furthermore, expression of ubiquitin S65A, a mutant that cannot be phosphorylated by PINK1, inhibited Parkin translocation to damaged mitochondria. These results explain a feed-forward mechanism of PINK1-mediated initiation of Parkin E3 ligase activity.
The kinase PINK1 and ubiquitin ligase Parkin can regulate the selective elimination of damaged mitochondria through autophagy (mitophagy). Because of the demand on lysosomal function by mitophagy, we ...investigated a role for the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, in this process. We show that during mitophagy TFEB translocates to the nucleus and displays transcriptional activity in a PINK1- and Parkin-dependent manner. MITF and TFE3, homologues of TFEB belonging to the same microphthalmia/transcription factor E (MiT/TFE) family, are similarly regulated during mitophagy. Unlike TFEB translocation after starvation-induced mammalian target of rapamycin complex 1 inhibition, Parkin-mediated TFEB relocalization required Atg9A and Atg5 activity. However, constitutively active Rag guanosine triphosphatases prevented TFEB translocation during mitophagy, suggesting cross talk between these two MiT/TFE activation pathways. Analysis of clustered regularly interspaced short palindromic repeats-generated TFEB/MITF/TFE3/TFEC single, double, and triple knockout cell lines revealed that these proteins partly facilitate Parkin-mediated mitochondrial clearance. These results illuminate a pathway leading to MiT/TFE transcription factor activation, distinct from starvation-induced autophagy, which occurs during mitophagy.
This paper is the first to use the method of instrumental variables to estimate the impact of obesity and severe obesity in youth. on U.S. medical care costs. We examine data from the Medical ...Expenditure Panel Survey for 2001–2015 and instrument for child BMI using the BMI of the child's biological mother. Instrumental variables estimates indicate that obesity in youth raises annual medical care costs by $907 (in 2015 dollars) or 92%, which is considerably higher than previous estimates of the association of youth obesity with medical costs. We find that obesity in youth significantly raises costs in all major categories of medical care: outpatient doctor visits, inpatient hospital stays, and prescription drugs. The costs of youth obesity are borne almost entirely by third‐party payers, which is consistent with substantial externalities of youth obesity, which in turn represents an economic rationale for government intervention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Gardner’s theory of multiple intelligences (MI) has been at the center of a long-running debate in educational psychology in terms of its generalizable validity. In this article, MI theory is ...discussed for a review of why and how MI theory may be contextually discussed for preservice teachers to learn about in their teacher education program. The semantic conceptual basis of intelligence in MI theory is discussed in comparison to learning styles theory with implications for the importance of the teaching of Universal Design for Learning and related frameworks in teacher education curriculum.
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