Background: Kidney transplant (KT) recipients are at risk of severe disease and high mortality from COVID-19, and vaccination offers some degree of protection. In this study, KT recipients' and controls' attitudes towards COVID-19 vaccination were examined.
Materials And Methods: In this cross-sectional survey-based study, the willingness and hesitancy towards COVID-19 vaccines in KT recipients and a control group from the general population were assessed via questionnaire.
Background: Peritoneal dialysis-associated peritonitis is a common and severe complication of peritoneal dialysis, associated with high morbidity and mortality. However, there's a lack of research on refractory peritonitis, which is difficult to manage and has a poor prognosis. Our study aimed to investigate factors affecting clinical outcomes in peritoneal dialysis patients with refractory peritonitis over a 12-year period at a medical faculty hospital in Turkey.
View Article and Find Full Text PDFPurpose Of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis.
Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases.
The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable.
View Article and Find Full Text PDFThe coronavirus disease 2019 (COVID-19) pandemic revealed that our understanding of infectious complications and strategies to mitigate severe infections in patients with glomerular diseases is limited. Beyond COVID-19, there are several infections that specifically impact care of patients receiving immunosuppressive measures. This review will provide an overview of six different infectious complications frequently encountered in patients with glomerular diseases, and will focus on recent achievements in terms of vaccine developments and understanding of the use of specific antimicrobial prophylaxis.
View Article and Find Full Text PDFGenetically encoded calcium indicators have proven useful for characterizing dorsal root ganglion neuron excitability in vivo. Challenges persist in achieving high spatial-temporal resolutions in vivo, however, due to deep tissue imaging and motion artifacts that may be limiting technical factors in obtaining measurements. Here we report an ex vivo imaging method, using a peripheral neuron-specific Advillin-GCaMP mouse line and electric field stimulation of dorsal root ganglion tissues, to assess the sensitivity of neurons en bloc.
View Article and Find Full Text PDFObjective: This study aimed to examine the temporal activation of NF-κB and its relationship to the development of pain-related sensitivity and behavioral changes in a non-invasive murine knee loading model of PTOA.
Method: Following knee injury NF-κB activity was assessed longitudinally via in vivo imaging in FVB. Cg-Tg (HIV-EGFP,luc)8Tsb/J mice.
Elastic fiber assembly is coordinated in part by fibulin-5, a matricellular protein. When fibulin-5 is not available to guide elastogenesis, elastin forms into disconnected globules instead of the dense elastic fiber core found in healthy tissues. Despite the growing evidence for a significant role of elastic fibers in tendon mechanics and the clinical relevance to cutis laxa, a human disease which can be caused by a mutation in the gene encoding fibulin-5, it is unknown how malformed elastic fibers affect tendon function.
View Article and Find Full Text PDFObjective: Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model.
Design: Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections.
In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues.
View Article and Find Full Text PDFViral RNA is recognized by innate immune receptors from two different families. In endolysosomal compartments, Toll-like receptors (TLRs) 3, 7 and 8 recognize either double-stranded RNA (dsRNA) or single-stranded RNA. In the cytoplasm, viral genomic RNA or transcriptional intermediates are recognized by DExD/H-box helicases RIG-I and MDA5.
View Article and Find Full Text PDFMelanoma differentiation-associated protein 5 (MDA5) detects viral dsRNA in the cytoplasm. On binding of RNA, MDA5 forms polymers, which trigger assembly of the signaling adaptor mitochondrial antiviral-signaling protein (MAVS) into its active fibril form. The molecular mechanism of MDA5 signaling is not well understood, however.
View Article and Find Full Text PDFMelanoma differentiation-associated gene-5 (MDA5) detects viral double-stranded RNA in the cytoplasm. RNA binding induces MDA5 to activate the signalling adaptor MAVS through interactions between the caspase recruitment domains (CARDs) of the two proteins. The molecular mechanism of MDA5 signalling is not well understood.
View Article and Find Full Text PDFToll-like receptor 9 (TLR9) recognizes microbial DNA in endolysosomal compartments. The ectodomain of TLR9 must be proteolytically cleaved by endosomal proteases to produce the active receptor capable of inducing an innate immune signal. We show that the cleaved TLR9 ectodomain is a monomer in solution and that DNA ligands with phosphodiester backbones induce TLR9 dimerization in a sequence-independent manner.
View Article and Find Full Text PDFNuclear pore complexes (NPCs) are 40-60 MDa protein assemblies embedded in the nuclear envelope of eukaryotic cells. NPCs exclusively mediate all transport between cytoplasm and nucleus. The nucleoporins that build the NPC are arranged in a stable core of module-like subcomplexes with eight-fold rotational symmetry.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2007
The nuclear pore complex (NPC) mediates macromolecular transport between the nucleus and the cytoplasm. Many NPC proteins (nucleoporins, Nups) are modified by phosphorylation. It is believed that phosphorylation regulates the breakdown of the nuclear envelope at mitosis and the disassembly of the NPC into different subcomplexes.
View Article and Find Full Text PDFIn MthK, a Ca2+-gated K+ channel from Methanobacterium thermoautotrophicum, eight cytoplasmic RCK domains form an octameric gating ring that controls the intracellular gate of the ion conduction pore. The binding of Ca2+ ions to the RCK domains alters the conformation of the gating ring, thereby opening the gate. In the present study, we examined the Ca2+- and pH-regulated gating and the rectifying conduction properties of MthK at the single-channel level.
View Article and Find Full Text PDFMthK is a Ca2+-gated K+ channel from Methanobacterium autotrophicum. The crystal structure of the MthK channel in a Ca2+-bound open state was previously determined at 3.3 A and revealed an octameric gating ring composed of eight intracellular ligand-binding RCK (regulate the conductance of K+) domains.
View Article and Find Full Text PDFNucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) whose complex architecture is generated from a set of only approximately 30 proteins, termed nucleoporins. Here, we explore the domain structure of Nup133, a nucleoporin in a conserved NPC subcomplex that is crucial for NPC biogenesis and is believed to form part of the NPC scaffold. We show that human Nup133 contains two domains: a COOH-terminal domain responsible for its interaction with its subcomplex through Nup107; and an NH2-terminal domain whose crystal structure reveals a seven-bladed beta-propeller.
View Article and Find Full Text PDFAntimicrobial susceptibility testing expense may be a significant portion of a clinical microbiology laboratory's budget. This study compares the BIOMIC VIDEO system (Giles Scientific, Inc., New York, N.
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