Career and dealing outcomes during the Coronavirus Widespread

To determine efficacy of peficitinib in reducing joint damage, and predictive factors affecting treatment response in Japanese patients with rheumatoid arthritis (RA).
This post hoc analysis used data from a placebo-controlled, phase 3 trial (RAJ4) of peficitinib in patients with RA and inadequate response to methotrexate. Erosion and joint space narrowing (JSN) was assessed at baseline and at Week 28/early termination (ET) of treatment using the van der Heijde-modified Sharp method. Univariate logistic regression analysis of change from baseline in modified total Sharp score identified predictive factors with significant treatment interaction; the effects of these factors on treatment response were further evaluated using a multivariate model.
The analyses included 481 patients. For most joint groups, peficitinib demonstrated reduced change from baseline at Week 28/ET in erosion and JSN scores versus placebo; a numerically greater effect was observed with peficitinib 150mg versus 100mg. Baseline C-reactive protein (CRP) and prednisolone dose were identified as clinically significant negative predictive factors treatment effect decreased as CRP or prednisolone dose increased, for both peficitinib doses.
Peficitinib 100mg and 150mg reduced joint damage versus placebo, across almost all joint groups. Higher baseline CRP and/or prednisolone dose were associated with reduced peficitinib efficacy.
NCT02305849.
NCT02305849.Mesenchymal stem cells (MSCs) exhibit self-renewal, multi-lineage differentiation potential and immunomodulatory properties, and are promising candidates for cellular therapy of various tissues. Despite the effective function of MSCs, the gradual loss of stem cell characteristics that occurs with repeated passages may significantly limit their therapeutic potential. A novel 3D shaking method was previously established to generate MSC spheroids in growth medium (GM-spheroids) and successfully maintain the multipotency of expanded MSCs, yet the expression of MSC-related genes was still low. In this study, we used a neurosphere culture technique to optimize the shaking culture method using human bone marrow-derived MSCs (BM-MSCs). MSC spheroids generated in neurosphere medium (NM-spheroids) maintained high expression of MSC-related genes during 3 weeks of prolonged shaking culture. Moreover, NM-spheroids generated from expanded MSCs showed high viability, upregulation of MSC-related and immune-related genes, and recovery of differentiation potential in vitro. Expanded adherent MSCs, GM-spheroids, and NM-spheroids were transplanted into a rat femur bone defect model to investigate their therapeutic potential in bone repair. Adherent MSCs and GM-spheroids showed delayed bone healing. In contrast, NM-spheroids showed high transplantation efficiency and enhanced bone regeneration. These data suggest that NM-spheroids generated using modified neurosphere culture conditions under continuous shaking recovered their stem cell characteristics in vitro and enhanced bone regeneration in vivo. Therefore, NM-spheroids should have great clinical potential for bone and tissue regenerative therapies as a stem cell-based biomaterial therapy.Michajlovia turdi (Yamaguti, 1939) (Digenea Brachylaimoidea) has been found from the Japanese thrush, Turdus cardis Temminck, 1831, in Hokkaido, the northernmost island of Japan. This is a rediscovery of M. turdi in Japan after approximately 80 years from the original description of the species as Leucochloridium turdiYamaguti, 1939. Here we redescribe the morphology of M. turdi and generate DNA barcodes for the species by sequencing nuclear ribosomal RNA (18S and 28S) and mitochondrial cytochrome c oxidase subunit I (COI) genes. Our molecular phylogenetic analysis was not effective at determining the taxonomic rank of Michajlovia in Brachylaimoidea, and consequently the genus remains as incertae sedis.
Excessive complement activation has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19), but the mechanisms leading to this response remain unclear.
We measured plasma levels of key complement markers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies against SARS-CoV-2 and seasonal human common cold coronaviruses (CCCs) in hospitalized patients with COVID-19 of moderate (n = 18) and critical severity (n = 37) and in healthy controls (n = 10).
We confirmed that complement activation is systemically increased in patients with COVID-19 and is associated with a worse disease outcome. We showed that plasma levels of C1q and circulating immune complexes were markedly increased in patients with severe COVID-19 and correlated with higher immunoglobulin (Ig) G titers, greater complement activation, and higher disease severity score. Additional analyses showed that the classical pathway was the main arm responsible for augmented complement activation in severe patients. In addition, we demonstrated that a rapid IgG response to SARS-CoV-2 and an anamnestic IgG response to the nucleoprotein of the CCCs were strongly correlated with circulating immune complex levels, complement activation, and disease severity.
These findings indicate that early, nonneutralizing IgG responses may play a key role in complement overactivation in severe COVID-19. Our work underscores the urgent need to develop therapeutic strategies to modify complement overactivation in patients with COVID-19.
These findings indicate that early, nonneutralizing IgG responses may play a key role in complement overactivation in severe COVID-19. Our work underscores the urgent need to develop therapeutic strategies to modify complement overactivation in patients with COVID-19.Mesenchymal stem cells (MSCs) are a promising cellular vehicle for transferring anti-cancer factors to malignant tumors. Currently, a variety of anti-cancer agents, including the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), have been loaded into MSCs derived from a range of sources through different engineering methods. These engineered MSCs exhibit enormous therapeutic potential for various cancers. To avoid the intrinsic defects of MSCs derived from tissues and the potential risk of viral vectors, TRAIL was site-specifically integrated into the ribosomal DNA (rDNA) locus of human-induced pluripotent stem cells (iPSCs) using a non-viral rDNA-targeting vector and transcription activator-like effector nickases (TALENickases). These genetically modified human iPSCs were differentiated into an unlimited number of homogeneous induced MSCs (TRAIL-iMSCs) that overexpressed TRAIL in both culture supernatants and cell lysates while maintaining MSC-like characteristics over continuous passages. We found that TRAIL-iMSCs significantly induced apoptosis in A375, A549, HepG2, and MCF-7 cells in vitro. After intravenous infusion, TRAIL-iMSCs had a prominent tissue tropism for A549 or MCF-7 xenografts and significantly inhibited tumor growth through the activation of apoptotic signaling pathways without obvious side effects in tumor-bearing mice models. Altogether, our results showed that TRAIL-iMSCs have strong anti-tumor effects in vitro and in vivo on a range of cancers. This study allows for the development of an unlimited number of therapeutic gene-targeted MSCs with stable quality and high homogeneity for cancer therapy, thus highlighting a universal and safe strategy for stem cell-based gene therapy with high potential for clinical applications.Healthcare is undergoing a profound technological and digital transformation and has become increasingly complex. It is important for burns professionals and researchers to adapt to these developments which may require new ways of thinking and subsequent new strategies. As Einstein has put it 'We must learn to see the world anew'. The relatively new scientific discipline "Complexity science" can give more direction to this and is the metaphorical open door that should not go unnoticed in view of the burn care of the future. Complexity sciences studies 'why the whole is more than the sum of the parts'. It studies how multiple separate components interact with each other and their environment and how these interactions lead to 'behavior of the system'. Biological systems are always part of smaller and larger systems and exhibit the behavior of adaptivity, hence the name complex adaptive systems. From the perspective of complexity science, a severe burn injury is an extreme disruption of the 'human body system'. But this disruption also applies to the systems at the organ and cellular level. All these systems follow principles of complex systems. Awareness of the scaling process at multilevel helps to understand and manage the complex situation when dealing with severe burn cases. GANT61 The aim of this paper is to create awareness of the concept of complexity and to demonstrate the value and possibilities of complexity science methods and tools for the future of burn care through examples from preclinical, clinical, and organizational perspective in burn care.At organelle-organelle contact sites, proteins have long been known to facilitate the rapid movement of lipids. Classically, this lipid transport involves the extraction of single lipids into a hydrophobic pocket on a lipid transport protein. Recently, a new class of lipid transporter has been described with physical characteristics that suggest these proteins are likely to function differently. They possess long hydrophobic tracts that can bind many lipids at once and physically span the entire gulf between membranes at contact sites, suggesting that they may act as bridges to facilitate bulk lipid flow. Here, we review what has been learned regarding the structure and function of this class of lipid transporters, whose best characterized members are VPS13 and ATG2 proteins, and their apparent coordination with other lipid-mobilizing proteins on organelle membranes. We also discuss the prevailing hypothesis in the field, that this type of lipid transport may facilitate membrane expansion through the bulk delivery of lipids, as well as other emerging hypotheses and questions surrounding these novel lipid transport proteins.
Study recruitment and retention of older adults in research studies is a major challenge. Enhancing understanding of individual differences in motivations to participate, and predictors of motivators, can serve the dual aims of facilitating the recruitment and retention of older adults, benefiting study validity, economy, and power.
Older adults (N = 472) past and potential participants were surveyed about motivations to participate in research, demographic, and individual difference measures (e.g., health status, cognitive difficulties). Latent class and clustering analyses explored motivation typologies, followed by regression models predicting individual motivators and typologies.
Older adults endorsed a diversity of research motivations, some of which could be predicted by individual difference measures (e.g., older participants were more motivated by the desire to learn new technology, participants without a college education were more motivated by financial compensation, and participants with greater self-reported cognitive problems were more likely to participate to gain cognitive benefit).