The incidence of acute kidney injury (AKI) is increasing every year and many patients with AKI admitted to the intensive care unit (ICU) require continuous renal replacement therapy (CRRT). This ...study compared and analyzed severity scoring systems to assess their suitability in predicting mortality in critically ill patients receiving CRRT. Data from 612 patients receiving CRRT in four ICUs of the Korea University Medical Center between January 2016 and November 2018 were retrospectively collected. The mean age of all patients was 67.6 ± 14.8 years, and the proportion of males was 59.6%. The endpoints were in-hospital mortality and 7-day mortality from the day of CRRT initiation to the date of death. The Program to Improve Care in Acute Renal Disease (PICARD), Demirjian's, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment (SOFA), Multiple Organ Dysfunction Score (MODS), and Liano's scores were used to predict mortality. The in-hospital and 7-day mortality rates in the study population were 72.7% and 45.1%, respectively. The area under the receiver operator characteristic curve (AUROC) revealed the highest discrimination ability for Demirjian's score (0.770), followed by Liano's score (0.728) and APACHE II (0.710). The AUROC curves for the SAPS 3, MODS, and PICARD were 0.671, 0.665, and 0.658, respectively. The AUROC of Demirjian's score was significantly higher than that of the other scores, except for Liano's score. The Hosmer-Lemeshow test on Demirjian's score showed a poor fit in our analysis; however, it was more acceptable than general severity scores. Kidney-specific severity scoring systems showed better performance in predicting mortality in critically ill patients receiving CRRT than general severity scoring systems.
Deformation-rate distributed acoustic sensing (DAS), made available by the unique designs of certain interrogator units, acquires seismic data that are theoretically equivalent to the along-fiber ...particle velocity motion recorded by geophones for scenarios involving elastic ground-fiber coupling. While near-elastic coupling can be achieved in cemented downhole installations, it is less obvious how to do so in lower-cost horizontal deployments. This investigation addresses this challenge by installing and freezing fiber in shallow backfilled trenches (to 0.1 m depth) to achieve improved coupling. This acquisition allows for a reinterpretation of processed deformation-rate DAS waveforms as a "filtered particle velocity" rather than the conventional strain-rate quantity. We present 1D and 2D filtering experiments that suggest 2D velocity-dip filtering can recover improved DAS data panels that exhibit clear surface and refracted arrivals. Data acquired on DAS fibers deployed in backfilled, frozen trenches were more repeatable over a day of acquisition compared to those acquired on a surface-deployed DAS fiber, which exhibited more significant amplitude variations and lower signal-to-noise ratios. These observations suggest that deploying fiber in backfilled, frozen trenches can help limit the impact of environmental factors that would adversely affect interpretations of time-lapse DAS observations.
Intestinal microbiota and kidney diseases Kim, Myung-Gyu; Yang, Jihyun; Jo, Sang-Kyung
Kidney research and clinical practice,
09/2021, Volume:
40, Issue:
3
Journal Article
Peer reviewed
Open access
Large microbial communities reside in the gut as an endogenous organ and interact with the host physiology through symbiotic relationships, affecting health. Recent advances in high-throughput ...sequencing techniques have made it possible to better understand these complex microbial communities and their effects on hosts. Animal and clinical studies have provided considerable evidence to show that the microbiota plays an important role in chronic kidney disease, acute kidney injury, nephrolithiasis, and kidney transplantation by altering the functions of the intestinal barrier, regulating local and systemic inflammation, controlling production of metabolic components, and affecting immune responses. Although the exact mechanism underlying the microbial shift and its impact on disease progression remains uncertain, the kidney-gut interaction clearly plays a significant role in onset and progression of kidney disease and, therefore, holds promise as a therapeutic target. Here, we review recent literature pertaining to the bidirectional relationship between microbes and humans in various kidney diseases and discuss the future direction of microbial research in nephrology.
SUMMARY
Ambient wavefield data acquired on existing (so-called ‘dark fibre’) optical fibre networks using distributed acoustic sensing (DAS) interrogators allow users to conduct a wide range of ...subsurface imaging and inversion experiments. In particular, recorded low-frequency (<2 Hz) surface-wave information holds the promise of providing constraints on the shear-wave velocity (VS) to depths exceeding 0.5 km. However, surface-wave analysis can be made challenging by a number of acquisition factors that affect the amplitudes of measured DAS waveforms. To illustrate these sensitivity challenges, we present a low-frequency ambient wavefield investigation using a DAS data set acquired on a crooked-line optical fibre array deployed in suburban Perth, Western Australia. We record storm-induced microseism energy generated at the nearby Indian Ocean shelf break and/or coastline in a low-frequency band (0.04−1.80 Hz) and generate high-quality virtual shot gathers (VSGs) through cross-correlation and cross-coherence interferometric analyses. The resulting VSG volumes clearly exhibit surface wave energy, though with significant along-line amplitude variations that are due to the combined effects of ambient source directivity, crooked-line acquisition geometry and the applied gauge length, fibre coupling, among other factors. We transform the observed VSGs into dispersion images using two different methods: phase shift and high-resolution linear Radon transform. These dispersion images are then used to estimate 1-D near-surface VS models using multichannel analysis of surface waves (MASW), which involves picking and inverting the estimated Rayleigh-wave dispersion curves using the particle-swarm optimization global optimization algorithm. The MASW inversion results, combined with nearby deep borehole information and 2-D elastic finite-difference modeling, show that low-frequency ambient DAS data constrain the VS model, including a low-velocity channel, to at least 0.5 km depth. Thus, this case study illustrates the potential of using DAS technology as a tool for undertaking large-scale surface wave analysis in urban geophysical and geotechnical investigations to depths exceeding 0.5 km.
Highly contagious respiratory diseases caused by viral infections are a constantly emerging threat, particularly the elderly with the higher risk of developing serious complications. Vaccines are the ...best strategy for protection against influenza-related diseases. However, the elderly has lower vaccine efficacy than young population and the age-driven decline of the influenza vaccine efficacy remains unresolved.
This study investigates the effect of an adjuvant, poly-γ-glutamic acid and alum (PGA/Alum) on vaccine efficacy in aged mice (18-months) and its mechanism is investigated using ovalbumin as a model antigen and a commercial pandemic H1N1 (pH1N1) flu vaccine. Antigen trafficking, dendritic cell (DC) activation, and the DC-mediated T cell activation were analyzed via in vivo imaging and flow cytometry. Antigen-specific humoral and cellular immune responses were evaluated in sera and splenocytes from the vaccinated mice. Also, we analyzed gene expression profiles of splenocytes from the vaccinated mice via single-cell transcriptome sequencing and evaluated the protective efficacy against pH1N1 virus challenge.
Aged mice had lower antigen trafficking and DC activation than younger mice (6-weeks), which was ameliorated by PGA/Alum with increased antigen uptake and DC activation leading to improved antigen-specific IFN-γ
CD8
T lymphocyte frequencies higher in the vaccinated aged mice, to a similar extent as PGA/Alum adjuvanted vaccine-immunized young mice. The results of single-cell transcriptome sequencing display that PGA/Alum also reduced the proportion of age-associated CD8
T cell subsets and gene levels of inhibitory regulators in CD8
T cells, which may play a role in the recovery of CD8
T cell activation. Finally, PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice were completely protected (100% survival) compared to aged mice immunized with vaccine only (0% survival) after pH1N1 virus challenge, akin to the efficacy of the vaccinated young mice (100% survival).
PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice showed a significant increase in vaccine efficacy compared to aged mice administered with vaccine only. The enhanced vaccine efficacy by PGA/Alum is associated with significant increases of activation of DCs and effector CD8
T cells and a decrease in age-associated CD8
T cell proportion of splenocytes. Collectively, PGA/Alum adjuvanted flu vaccine may be a promising vaccine candidate for the elderly.
Acute kidney injury (AKI) increases the risk of end stage renal disease among the elderly, but the precise underlying mechanism is unknown. We investigated the effects of aging on AKI-to-chronic ...kidney disease (CKD) transition, focusing on renal inflammation. Aged and young C57BL/6 mice were subjected to bilateral ischemia-reperfusion injury (IRI). Baseline proinflammatory cytokine levels of kidneys were elevated in aged mice. After IRI, aged mice also showed persistent M1 dominant inflammation, with increased proinflammatory cytokines during the recovery phase. Persistent M1 inflammation was associated with blunted activation of CSF-1/IRF4 signal for M1/M2 polarization, but in vitro macrophage polarization with cytokine stimulation was not different between young and aged mononuclear cells. The tubular expressions of cell cycle arrest markers increased in aged mice during recovery phase, and in vitro transwell experiments showed that mononuclear cells or M1 macrophages co-cultured with arrested proximal tubular cells at G1 phase significantly impaired M2 polarization, suggesting that prolonged G1 arrest might be involved in persistent M1 inflammation in aged mice. Finally, M1 dominant inflammation in aged mice resulted in fibrosis progression. Our data show that impaired M2 polarization partially driven by senescent tubule cells with cell-cycle arrest may lead to an accelerated progression to CKD in the elderly.
The absence of children in tourism research has been identified by past scholars but the rising attention on Asians consumers in tourism has also implied that the voices of Chinese children need to ...be heard. This study triangulates 14 young Malaysian Chinese children's drawings of their favorite family holidays with open-ended interview questions. The drawings were analyzed using the five thematic levels according to a model of analysis of children's drawings. Findings revealed the collectivistic Confucian value of family and education during family vacations, but also highlight what Chinese children conceptualized as fun holiday activities. A number of suggestions are provided for future research and for tourism practitioners to provide memorable holiday experiences for their young travelers.
Emerging evidence suggests that intestinal dysbiosis contributes to systemic inflammation and cardiovascular diseases in dialysis patients. The purpose of this study was to evaluate the effects of ...probiotic supplementation on various inflammatory parameters in hemodialysis (HD) patients.
Twenty-two patients with maintenance HD were enrolled. These patients were treated twice a day with 2.0 ×1010 colony forming units of a combination of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 3 months. The microbiome and fecal short-chain fatty acids (SCFAs) were analyzed. The percentages of CD14+ CD16+ proinflammatory monocytes and CD4+ CD25+ regulatory T-cells (Tregs) before and after probiotic supplementation were determined by flow cytometry. Serum levels of calprotectin and cytokine responses upon lipopolysaccharide (LPS) challenge were compared before and after probiotic supplementation.
Fecal SCFAs increased significantly after probiotic supplementation. Serum levels of calprotectin and interleukin 6 upon LPS stimulation significantly decreased. The anti-inflammatory effects of probiotics were associated with a significant increase in the percentage of CD4+ CD25+ Tregs (3.5% vs. 8.6%, p < 0.05) and also with a decrease of CD14+ CD16+ proinflammatory monocytes (310/ mm2 vs. 194/mm2 , p < 0.05).
Probiotic supplementation reduced systemic inflammatory responses in HD patients and this effect was associated with an increase in Tregs and a decrease in proinflammatory monocytes. Hence, targeting intestinal dysbiosis might be a novel strategy for decreasing inflammation and cardiovascular risks in HD patients.
Osteoporosis and bone disorders related to the metabolic syndrome are often associated with adipokines secreted by adipocytes in bone. Adiponectin, a type of adipokine, is a regulator of immune ...responses and metabolic processes, but its role in bone biology remains uncertain. We investigated the role of adiponectin in bone metabolism using adiponectin-deficient mice
and
. Adiponectin-deficient mice exhibited reduced bone mass and increased adiposity. Adiponectin-deficient calvarial cells were prone to differentiate into adipocytes rather than osteoblasts. Although bone marrow macrophages (BMMs) from adiponectin-deficient mice had low osteoclastogenic potential as osteoclast precursors with increasing interferon regulatory factor 5 expression, under co-culture conditions of calvarial cells and BMMs, the enhanced receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio of adiponectin-deficient mesenchymal progenitor cells facilitated osteoclast differentiation. In addition, increased RANKL/OPG ratio was observed in the bone marrow extracellular fluid of adiponectin-deficient mice compared to that of wild-type mice. Notably, recombinant adiponectin treatment enhanced RANKL-induced osteoclast differentiation from BMMs but up-regulated OPG production in recombinant adiponectin-exposed calvarial cells, which inhibited osteoclast differentiation. Taken together, these results suggest that adiponectin plays an inhibitory role in bone metabolism through cross talk between precursor cells of both osteoclasts and osteoblasts by regulating RANKL/OPG ratio in the bone marrow microenvironment.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), had a major impact on both the global health and economy. Numerous ...virus-neutralizing antibodies were developed against the S1 subunit of SARS-CoV-2 spike (S) protein to block viral binding to host cells and were authorized for control of the COVID-19 pandemic. However, frequent mutations in the S1 subunit of SARS-CoV-2 enabled the emergence of immune evasive variants. To address these challenges, broadly neutralizing antibodies targeting the relatively conserved S2 subunit and its epitopes have been investigated as antibody therapeutics and universal vaccines.
We initiated this study by immunizing BALB/c mice with β-propiolactone-inactivated SARS-CoV-2 (IAV) to generate B-cell hybridomas. These hybridomas were subsequently screened using HEK293T cells expressing the S2-ECD domain. Hybridomas that produced anti-S2 antibodies were selected, and we conducted a comprehensive evaluation of the potential of these anti-S2 antibodies as antiviral agents and versatile tools for research and diagnostics.
In this study, we present a novel S2-specific antibody, 4A5, isolated from BALB/c mice immunized with inactivated SARS-CoV-2. 4A5 exhibited specific affinity to SARS-CoV-2 S2 subunits compared with those of other β-CoVs. 4A5 bound to epitope segment F1109-V1133 between the heptad-repeat1 (HR1) and the stem-helix (SH) region. The 4A5 epitope is highly conserved in SARS-CoV-2 variants, with a significant conformational feature in both pre- and postfusion S proteins. Notably, 4A5 exhibited broad neutralizing activity against variants and triggered Fc-enhanced antibody-dependent cellular phagocytosis.
These findings offer a promising avenue for novel antibody therapeutics and insights for next-generation vaccine design. The identification of 4A5, with its unique binding properties and broad neutralizing capacity, offers a potential solution to the challenge posed by SARS-CoV-2 variants and highlights the importance of targeting the conserved S2 subunit in combating the COVID-19.
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