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Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association. Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL. Results: Higher HL scores B = 0.13 (95% CI = 0.06–0.21, p = 0.001) and HDK scores B = 0.58 (95% CI = 0.31–0.85, p = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = −6.12 (95% CI = −7.66 to – 4.58, p = 0.001) and FCoV-19 B = −0.91 (95% CI = −1.03 to – 0.80, p = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary. Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient's KDQOL during the pandemic. [ABSTRACT FROM AUTHOR]

The histone deacetylases (HDACs) are a superfamily of chromatin-modifying enzymes that silence transcription through the modification of histones. Among them, HDAC3 is unique in that interaction with nuclear receptor corepressors 1 and 2 (NCoR1/2) is required to engage its catalytic activity.sup.1-3. However, global loss of HDAC3 also results in the repression of transcription, the mechanism of which is currently unclear.sup.4-8. Here we report that, during the activation of macrophages by lipopolysaccharides, HDAC3 is recruited to activating transcription factor 2 (ATF2)-bound sites without NCoR1/2 and activates the expression of inflammatory genes through a non-canonical mechanism. By contrast, the deacetylase activity of HDAC3 is selectively engaged at ATF3-bound sites that suppress Toll-like receptor signalling. Loss of HDAC3 in macrophages safeguards mice from lethal exposure to lipopolysaccharides, but this protection is not conferred upon genetic or pharmacological abolition of the catalytic activity of HDAC3. Our findings show that HDAC3 is a dichotomous transcriptional activator and repressor, with a non-canonical deacetylase-independent function that is vital for the innate immune system. During the activation of mouse macrophages by lipopolysaccharides, histone deacetylase 3 controls inflammatory responses by both repressing and activating gene transcription depending on its differential association with transcription factors., Author(s): Hoang C. B. Nguyen [sup.1] [sup.2] , Marine Adlanmerini [sup.1] [sup.2] , Amy K. Hauck [sup.1] [sup.2] , Mitchell A. Lazar [sup.1] [sup.2] Author Affiliations: (1) Institute for Diabetes, [...]

BackgroundThe COVID-19 pandemic has imposed a heavy burden on health care systems and governments. Health literacy (HL) and eHealth literacy (as measured by the eHealth Literacy Scale [eHEALS]) are recognized as strategic public health elements but they have been underestimated during the pandemic. HL, eHEALS score, practices, lifestyles, and the health status of health care workers (HCWs) play crucial roles in containing the COVID-19 pandemic. ObjectiveThe aim of this study is to evaluate the psychometric properties of the eHEALS and examine associations of HL and eHEALS scores with adherence to infection prevention and control (IPC) procedures, lifestyle changes, and suspected COVID-19 symptoms among HCWs during lockdown. MethodsWe conducted an online survey of 5209 HCWs from 15 hospitals and health centers across Vietnam from April 6 to April 19, 2020. Participants answered questions related to sociodemographics, HL, eHEALS, adherence to IPC procedures, behavior changes in eating, smoking, drinking, and physical activity, and suspected COVID-19 symptoms. Principal component analysis, correlation analysis, and bivariate and multivariate linear and logistic regression models were used to validate the eHEALS and examine associations. ResultsThe eHEALS had a satisfactory construct validity with 8 items highly loaded on one component, with factor loadings ranked from 0.78 to 0.92 explaining 76.34% of variance; satisfactory criterion validity as correlated with HL (ρ=0.42); satisfactory convergent validity with high item-scale correlations (ρ=0.80-0.84); and high internal consistency (Cronbach α=.95). HL and eHEALS scores were significantly higher in men (unstandardized coefficient [B]=1.01, 95% CI 0.57-1.45, P

The grain-scale nature of evolution of the coefficient of lateral earth pressure at rest (K0) with interparticle friction (µp) is poorly understood. This study aims to use discrete element method simulations of vertical one-dimensional compression on both face centred cubic (FCC) samples and random monodisperse (RM) samples to link K0 and µp, and the results show that K0 increases with reductions in interparticle friction. Although K0 is dependent upon the sample density, patterns of evolutions with strain levels are likely to be unchanged with initial confining pressures. The stress-induced fabric becomes more anisotropic for samples with high values of the interparticle friction. The percentage of particles with a high value of the normal contact force increases with increasing strain levels as the interparticle friction increases in the simulations.

Obesity occurs when energy expenditure is outweighed by energy intake. Tuberal hypothalamic nuclei, including the arcuate nucleus (ARC), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH), control food intake and energy expenditure. Here we report that, in contrast with females, male mice lacking circadian nuclear receptors REV-ERBα and -β in the tuberal hypothalamus (HDKO mice) gained excessive weight on an obesogenic high-fat diet due to both decreased energy expenditure and increased food intake during the light phase. Moreover, rebound food intake after fasting was markedly increased in HDKO mice. Integrative transcriptomic and cistromic analyses revealed that such disruption in feeding behavior was due to perturbed REV-ERB-dependent leptin signaling in the ARC. Indeed, in vivo leptin sensitivity was impaired in HDKO mice on an obesogenic diet in a diurnal manner. Thus, REV-ERBs play a crucial role in hypothalamic control of food intake and diurnal leptin sensitivity in diet-induced obesity. [ABSTRACT FROM AUTHOR]

The first fully integrated 2D CMOS imaging sensor with on-chip signal processing for applications in laser Doppler blood flow (LDBF) imaging has been designed and tested. To obtain a space efficient design over 64 x 64 pixels means that standard processing electronics used off-chip cannot be implemented. Therefore the analog signal processing at each pixel is a tailored design for LDBF signals with balanced optimization for signal-to-noise ratio and silicon area. This custom made sensor offers key advantages over conventional sensors, viz. the analog signal processing at the pixel level carries out signal normalization; the AC amplification in combination with an anti-aliasing filter allows analog-to-digital conversion with a low number of bits; low resource implementation of the digital processor enables on-chip processing and the data bottleneck that exists between the detector and processing electronics has been overcome. The sensor demonstrates good agreement with simulation at each design stage. The measured optical performance of the sensor is demonstrated using modulated light signals and in vivo blood flow experiments. Images showing blood flow changes with arterial occlusion and an inflammatory response to a histamine skin-prick demonstrate that the sensor array is capable of detecting blood flow signals from tissue. [ABSTRACT FROM AUTHOR]

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB). Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18-85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety. Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with "unchanged/more" physical activity (p < 0.001), or "unchanged/more" drinking (p < 0.001 for only anxiety), or "unchanged/healthier" eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, "never/stopped/less" physical activity, drinking, "less healthy" eating, and low PB score, respectively. Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors. [ABSTRACT FROM AUTHOR]

Increasing resistance in Plasmodium falciparum to artemisinins and their artemisinin combination therapy (ACT) partner drugs jeopardizes effective antimalarial treatment. Resistance is worst in the Greater Mekong subregion. Monitoring genetic markers of resistance can help to guide antimalarial therapy. Markers of resistance to artemisinins ( PfKelch mutations), mefloquine (amplification of P. falciparum multidrug resistance-1 [ PfMDR1 ]), and piperaquine ( PfPlasmepsin2/3 amplification and specific P. falciparum chloroquine resistance transporter [ PfCRT ] mutations) were assessed in 6,722 P. falciparum samples from Vietnam, Lao People's Democratic Republic (PDR), Cambodia, Thailand, and Myanmar between 2007 and 2019. Against a high background prevalence of PfKelch mutations, PfMDR1 and PfPlasmepsin2/3 amplification closely followed regional drug pressures over time. PfPlasmepsin2/3 amplification preceded piperaquine resistance-associated PfCRT mutations in Cambodia and reached a peak prevalence of 23/28 (82%) in 2015. This declined to 57/156 (38%) after first-line treatment was changed from dihydroartemisinin-piperaquine to artesunate-mefloquine (ASMQ) between 2014 and 2017. The frequency of PfMDR1 amplification increased from 0/293 (0%) between 2012 and 2017 to 12/156 (8%) in 2019. Amplification of PfMDR1 and PfPlasmepsin2/3 in the same parasites was extremely rare (4/6,722 [0.06%]) and was dispersed over time. The mechanisms conferring mefloquine and piperaquine resistance may be counterbalancing. This supports the development of ASMQ plus piperaquine as a triple artemisinin combination therapy.

Post-transcriptional regulation of RNA stability is a key step in gene expression control. We describe a regulatory program, mediated by the RNA binding protein TARBP2, that controls RNA stability in the nucleus. TARBP2 binding to pre-mRNAs results in increased intron retention, subsequently leading to targeted degradation of TARBP2-bound transcripts. This is mediated by TARBP2 recruitment of the m 6 A RNA methylation machinery to its target transcripts, where deposition of m 6 A marks influences the recruitment of splicing regulators, inhibiting efficient splicing. Interactions between TARBP2 and the nucleoprotein TPR then promote degradation of these TARBP2-bound transcripts by the nuclear exosome. Additionally, analysis of clinical gene expression datasets revealed a functional role for TARBP2 in lung cancer. Using xenograft mouse models, we find that TARBP2 affects tumor growth in the lung and that this is dependent on TARBP2-mediated destabilization of ABCA3 and FOXN3. Finally, we establish ZNF143 as an upstream regulator of TARBP2 expression., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARγ ligand, in a PPARγ-dependent manner. Moreover, PPARγ is required for macrophage respiration even in the absence of exogenous ligand. Unexpectedly, the absence of PPARγ dramatically affects the oxidation of glutamine. Both glutamine and PPARγ have been implicated in alternative activation (AA) of macrophages, and PPARγ was required for interleukin 4 (IL4)-dependent gene expression and stimulation of macrophage respiration. Indeed, unstimulated macrophages lacking PPARγ contained elevated levels of the inflammation-associated metabolite itaconate and express a proinflammatory transcriptome that, remarkably, phenocopied that of macrophages depleted of glutamine. Thus, PPARγ functions as a checkpoint, guarding against inflammation, and is permissive for AA by facilitating glutamine metabolism. However, PPARγ expression is itself markedly increased by IL4. This suggests that PPARγ functions at the center of a feed-forward loop that is central to AA of macrophages., (© 2018 Nelson et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Resection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection., Results: MiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively)., Materials and Methods: We employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples., Conclusions: After CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation.

Transfer RNAs (tRNAs) are primarily viewed as static contributors to gene expression. By developing a high-throughput tRNA profiling method, we find that specific tRNAs are upregulated in human breast cancer cells as they gain metastatic activity. Through loss-of-function, gain-of-function, and clinical-association studies, we implicate tRNAGluUUC and tRNAArgCCG as promoters of breast cancer metastasis. Upregulation of these tRNAs enhances stability and ribosome occupancy of transcripts enriched for their cognate codons. Specifically, tRNAGluUUC promotes metastatic progression by directly enhancing EXOSC2 expression and enhancing GRIPAP1-constituting an "inducible" pathway driven by a tRNA. The cellular proteomic shift toward a pro-metastatic state mirrors global tRNA shifts, allowing for cell-state and cell-type transgene expression optimization through codon content quantification. TRNA modulation represents a mechanism by which cells achieve altered expression of specific transcripts and proteins. TRNAs are thus dynamic regulators of gene expression and the tRNA codon landscape can causally and specifically impact disease progression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Upon exposure to stress, tRNAs are enzymatically cleaved, yielding distinct classes of tRNA-derived fragments (tRFs), yielding distinct classes of tRFs. We identify a novel class of tRFs derived from tRNA(Glu), tRNA(Asp), tRNA(Gly), and tRNA(Tyr) that, upon induction, suppress the stability of multiple oncogenic transcripts in breast cancer cells by displacing their 3' untranslated regions (UTRs) from the RNA-binding protein YBX1. This mode of post-transcriptional silencing is sequence specific, as these fragments all share a common motif that matches the YBX1 recognition sequence. Loss-of-function and gain-of-function studies, using anti-sense locked-nucleic acids (LNAs) and synthetic RNA mimetics, respectively, revealed that these fragments suppress growth under serum-starvation, cancer cell invasion, and metastasis by breast cancer cells. Highly metastatic cells evade this tumor-suppressive pathway by attenuating the induction of these tRFs. Our findings reveal a tumor-suppressive role for specific tRNA-derived fragments and describe a molecular mechanism for their action. This transcript displacement-based mechanism may generalize to other tRNA, ribosomal-RNA, and sno-RNA fragments., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The first fully integrated 2D CMOS imaging sensor with on-chip signal processing for applications in laser Doppler blood flow (LDBF) imaging has been designed and tested. To obtain a space efficient design over 64 × 64 pixels means that standard processing electronics used off-chip cannot be implemented. Therefore the analog signal processing at each pixel is a tailored design for LDBF signals with balanced optimization for signal-to-noise ratio and silicon area. This custom made sensor offers key advantages over conventional sensors, viz. the analog signal processing at the pixel level carries out signal normalization; the AC amplification in combination with an anti-aliasing filter allows analog-to-digital conversion with a low number of bits; low resource implementation of the digital processor enables on-chip processing and the data bottleneck that exists between the detector and processing electronics has been overcome. The sensor demonstrates good agreement with simulation at each design stage. The measured optical performance of the sensor is demonstrated using modulated light signals and in vivo blood flow experiments. Images showing blood flow changes with arterial occlusion and an inflammatory response to a histamine skin-prick demonstrate that the sensor array is capable of detecting blood flow signals from tissue.