Ibsenogden0921

Heterogeneity was substantial (I²≥65%).

The success rate of GC discontinuation after bridging as part of initial treatment of RA has been described in a limited number of studies. Reports on observational cohorts did not answer the research question. In clinical trials, protocolised discontinuation was mostly successful, although 22% of the patients who started GC bridging therapy still or again used GC at 12 months, and 10% at 24 months.

The success rate of GC discontinuation after bridging as part of initial treatment of RA has been described in a limited number of studies. Reports on observational cohorts did not answer the research question. In clinical trials, protocolised discontinuation was mostly successful, although 22% of the patients who started GC bridging therapy still or again used GC at 12 months, and 10% at 24 months.

Neonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%-16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function.

A genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. selleckchem Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography.

We identified

as a novel fetal susceptibility gene, with decreased cardiac expression of

associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded by

, have abnormal connectivity and Ca

homoeostasis in culture, as well as decreased cell surface expression of the Ca

1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals.

Our study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.

Our study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.

Remote care and telehealth have the potential to expand healthcare access, and the COVID-19 pandemic has called for alternative solutions to conventional face-to-face follow-up and monitoring. However, guidance is needed on the integration of telehealth into clinical care of people with rheumatic and musculoskeletal diseases (RMD).

To develop EULAR points to consider (PtC) for the development, prioritisation and implementation of telehealth for people with RMD.

A multidisciplinary EULAR task force (TF) of 30 members from 14 European countries was established, and the EULAR standardised operating procedures for development of PtC were followed. A systematic literature review was conducted to support the TF in formulating the PtC. The level of agreement among the TF was established by anonymous online voting.

Four overarching principles and nine PtC were formulated. The use of telehealth should be tailored to patient's needs and preferences. The healthcare team should have adequate equipment and training and have telecommunication skills. Telehealth can be used in screening for RMD as preassessment in the referral process, for disease monitoring and regulation of medication dosages and in some non-pharmacological interventions. People with RMD should be offered training in using telehealth, and barriers should be resolved whenever possible.The level of agreement to each statement ranged from 8.5 to 9.8/10.

The PtC have identified areas where telehealth could improve quality of care and increase healthcare access. Knowing about drivers and barriers of telehealth is a prerequisite to successfully establish remote care approaches in rheumatologic clinical practice.

The PtC have identified areas where telehealth could improve quality of care and increase healthcare access. Knowing about drivers and barriers of telehealth is a prerequisite to successfully establish remote care approaches in rheumatologic clinical practice.

To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets.

We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and ~1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen).

We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in

(rs140675301-A) that is independent of reported non-coding

-variants, increases the risk of seropositive RA 2.27-fold (p=2.1×10

), more than the rs2476601-A missense variant in

(OR=1.59, p=1.3×10

).

rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in

increases seropositive RA risk (OR=1.35, p=6.6×10

). Independent missense variants in

(rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10

-10

) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4.

Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.

Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.During the COVID-19 pandemic, restrictions for visitors and caregivers in healthcare settings and long-term care (LTC) facilities were enacted in the larger context of public health policies that included physical distancing and shelter-in-place orders. Older persons residing in LTC facilities constituted over half of the mortality statistics across Canada during the first wave of the COVID-19 pandemic. Using the poststructuralist work of Agamben, Foucault and Mbembe we conducted a thematic analysis on news reports. The extracts of media stories presented in our paper suggest that the scholarship on (bio)power and necropolitics is central for understanding the ways the COVID-19 crisis reveals the pragmatic priorities-and the 'health' and political values-that undergird the moral imagination of the public, including the educated classes of advanced Western democracies. Our critical analysis shows that by isolating individuals who were sick, fragile, and biologically and socially vulnerable, undifferentiated population management policies like social distancing, when piled on the structural weakness of health systems, reproduced inequities and risk for those in need of medical care, advocacy, and social companionship in acute moments of illness, death and grief. Considering the unprecedented deployment of governmental power via public health interventions based on social regulation to protect the population during the crisis-how can we understand so much death and suffering among the most vulnerable?This paper examines two Indian texts, Anand Gandhi's film The Ship of Theseus (2012) and Manjula Padmanabhan's play Harvest (1998), which deal with complex biopolitical and geopolitical questions around organ transplantation, for their treatment of corporeal, geopolitical and ethical borders.By dramatising the lives of carriers who are both receivers and donors, the texts enact boundaries, visible and invisible, from both sides. I focus on the carrier of the diseased organ-already a stranger, as Jean-Luc Nancy describes his own failing heart in L'Intrus (2000)-and the carrier of the alien organ and show how these raise moral and ethical questions around organ transplantation. I first argue that these texts foreground biopolitical quandaries even as they narrate the moral economies of transplantation. I then delineate the ways in which the texts employ a posthuman imaginary. The texts raise questions around organ transplantation that while emanating from the invasion of corporeal borders also reflect the permeability of social borders, and while doing so, posit the human in today's medicalised terrain as a fragmented, multiple self that is embedded in the environment and co-evolves with it.By addressing the altered sense of self of the 'body-in-transplant' through a posthumanist lens that accounts for relationality and the acknowledgement of a plural self, the paper hopes to make a contribution to a better understanding of the vulnerable post-transplant patient.Is biology and knowing biological ancestral information essential to the construction of identity? Bioethicist James David Velleman believes this is the case and argues that donor gamete conception is immoral because a portion of genetic heritage will be unknown. Velleman is critical of sperm donation and the absence of a biological father in donor-assisted families. His bioethical work, specifically the 2005 article 'Family History', is oft-cited in articles debating the ethics surrounding gamete donations and diverse family formations. However, I wonder to what extent Velleman's ethical stance is exhibited in contemporary culture? Velleman suggests that innate knowledge of bio-superiority helps readers and audiences appreciate the importance of biological family structures in literature and film; he says, 'When people deny the importance of biological ties, I wonder how they can read world literature with any comprehension' (2005, 369). Velleman understands the stories of Oedipus, Moses, Telemachus and Luke Skywalker as demonstrating a universal cultural comprehension that genetics are essential to identity construction. I adopt Velleman's list of stories and ask if they really can support an antidonation sentiment and suggest that most of the stories actually support diverse family structures. By exploring the significance of story-telling in cultural understandings of family and identity, it is possible to identify the ways in which story-telling can impact how society negotiates complex issues such as assisted reproduction, donor conception and donor industry regulation.