Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,539 adults in the Chronic Renal Insufficiency Cohort Study. EXPOSURE: Frailty status assessed using 5 criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. OUTCOME: Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death. ANALYTICAL APPROACH: Cause-specific hazards models. RESULTS: At study entry, the participants' mean age was 62 years, 46% were female, the mean estimated glomerular filtration rate was 45.4mL/min/1.73m2, and the median urine protein was 0.2mg/day. Frailty status was as follows: 12% frail, 51% prefrail, and 37% nonfrail. Over a median follow-up of 11.4 years, there were 393 atherosclerotic events, 413 heart failure events, 497 deaths, and 132 cardiovascular deaths. In multivariable regression analyses, compared with nonfrailty, both frailty and prefrailty status were each associated with higher risk of an atherosclerotic event (HR, 2.03 [95% CI, 1.41-2.91] and 1.77 [95% CI, 1.35-2.31], respectively) and incident heart failure (HR, 2.22 [95% CI, 1.59-3.10] and 1.39 [95% CI, 1.07-1.82], respectively), as well as higher risk of all-cause death (HR, 2.52 [95% CI, 1.84-3.45] and 1.76 [95% CI, 1.37-2.24], respectively) and cardiovascular death (HR, 3.01 [95% CI, 1.62-5.62] and 1.78 [95% 1.06-2.99], respectively). LIMITATIONS: Self-report of aspects of the frailty assessment and comorbidities, which may have led to bias in some estimates. CONCLUSIONS: In adults with CKD, frailty status was associated with higher risk of cardiovascular events and mortality. Future studies are needed to evaluate the impact of interventions to reduce frailty on cardiovascular outcomes in this population. PLAIN-LANGUAGE SUMMARY: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes. We sought to evaluate the association of frailty status with cardiovascular events and death in adults with CKD. Frailty was assessed according to the 5 phenotypic criteria detailed by Fried and colleagues. Among 2,539 participants in the CRIC Study, we found that 12% were frail, 51% were prefrail, and 37% were nonfrail. Frailty status was associated with an increased risk of atherosclerotic events, incident heart failure, and death.

Significance of Arterial Spin Labeling for Reducing Biopsies in Patients With Kidney Allograft Dysfunction.

BACKGROUND: Although biopsy is often entailed for managing patients with kidney allograft dysfunction, it is associated with potential complications of severe hemorrhage. Arterial spin labeling (ASL) is a non-invasive technique that assesses tissue perfusion. PURPOSE: To assess the utility of ASL for the discrimination of patients with post-transplant allograft dysfunction who do not need biopsy from those who need. STUDY TYPE: Prospective. SUBJECTS: Forty-six patients (34 males/12 females, aged 38.8 ± 9.5 years) with kidney allograft dysfunction, including 31 in which biopsy directly lead to changes in management (NECESSARY group) and 15 in which clinical management did not alter after biopsy (UNNECESSARY group). FIELD STRENGTH/SEQUENCE: 3.0 T and 3D fast-spin echo sequence. ASSESSMENT: All patients underwent both ASL scan and biopsies. The serum creatinine, proteinuria, pathologic results, and cortical ASL readings were obtained and compared between the two groups. STATISTICAL ANALYSES: Chi-square test, independent student t-test, Mann-Whitney U test, receiver-operating characteristic curve. A two-tailed P < 0.05 denoted statistical significance. RESULTS: The NECESSARY group presented with significantly elevated serum creatinine as compared with the UNNECESSARY group (1.87 ± 0.56 mg/dL vs. 1.31 ± 0.37 mg/dL). The acute composite score was significantly higher in the NECESSARY group than that in the UNNECESSARY group (7 [4-8] vs. 1 [0-2]). Cortical ASL in the NECESSARY group was significantly decreased as compared with the UNNECESSARY group (108.06 [69.96-134.92] mL/min/100 g vs. 153.48 [113.19-160.37] mL/min/100 g). Serum creatinine differentiated UNNCESSARY group from the NECESSARY group with an area under the curve (AUC) and specificity of 0.79 and 54.84%, respectively. By comparison, the cortical ASL yielded an AUC of 0.75 and a specificity of 70.97%. Notably, the specificity was increased to 90.30% by combined use of serum creatinine and cortical ASL. DATA CONCLUSION: The combined use of ASL and serum creatinine yielded a high specificity for selecting patients who may not need allograft biopsy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Joint Active and Passive Beamforming in RIS-Assisted Secure ISAC Systems.

This paper investigates joint beamforming in a secure integrated sensing and communications (ISAC) system assisted by reconfigurable intelligent surfaces (RIS). The system communicates with legitimate downlink users, detecting a potential target, which is a potential eavesdropper attempting to intercept the downlink communication information from the base station (BS) to legitimate users. To enhance the physical-layer secrecy of the system, we design and introduce interference signals at the BS to disrupt eavesdroppers' attempts to intercept legitimate communication information. The BS simultaneously transmits communication and interference signals, both utilized for communication and sensing to guarantee the sensing and communication quality. By jointly optimizing the BS active beamformer and the RIS passive beamforming matrix, we aim to maximize the achievable secrecy rate and radiation power of the system. We develop an effective scheme to find the active beamforming matrix through fractional programming (FP) and semi-definite programming (SDP) techniques and obtain the RIS phase shift matrix via a local search technique. Simulation results validate the effectiveness of the proposed methods in enhancing communication and sensing performance. Additionally, the results demonstrate the effectiveness of introducing the interference signals and RIS in enhancing the physical-layer secrecy of the ISAC system.

Structural Optimization and Performance of a Low-Frequency Double-Shell Type-IV Flexural Hydroacoustic Transducer.

To amplify the displacement of the radiation shell, a double-shell type-IV curved hydroacoustic transducer was proposed. Through Ansys finite element simulation, the vibration modes of the transducer in different stages and the harmonic response characteristics in air and water were studied, and the bandwidth emission of the hydroacoustic transducer was achieved. By optimizing the size of each component, the resonant frequency of the transducer is 740 Hz, the maximum conductivity was 0.66 mS, and the maximum transmitting voltage response was 130 dB. According to the optimized parameters, a longitudinal acoustic transducer prototype was manufactured, and a physical test was conducted in an anechoic pool. The obtained resonant frequency was 750 Hz, the maximum conductivity was 0.44 mS, the maximum transmitting voltage response was 129.25 dB, and the maximum linear dimension was 250 mm, which match the simulated value of the virtual prototype and meet the expected requirements.

AdNAC20 Regulates Lignin and Coumarin Biosynthesis in the Roots of Angelica dahurica var. Formosana.

Angelica dahurica var. formosana (ADF), which belongs to the Umbelliferae family, is one of the original plants of herbal raw material Angelicae Dahuricae Radix. ADF roots represent an enormous biomass resource convertible for disease treatment and bioproducts. But, early bolting of ADF resulted in lignification and a decrease in the coumarin content in the root, and roots lignification restricts its coumarin for commercial utility. Although there have been attempts to regulate the synthesis ratio of lignin and coumarin through biotechnology to increase the coumarin content in ADF and further enhance its commercial value, optimizing the biosynthesis of lignin and coumarin remains challenging. Based on gene expression analysis and phylogenetic tree profiling, AdNAC20 as the target for genetic engineering of lignin and coumarin biosynthesis in ADF was selected in this study. Early-bolting ADF had significantly greater degrees of root lignification and lower coumarin contents than that of the normal plants. In this study, overexpression of AdNAC20 gene plants were created using transgenic technology, while independent homozygous transgenic lines with precise site mutation of AdNAC20 were created using CRISPR/Cas9 technology. The overexpressing transgenic ADF plants showed a 9.28% decrease in total coumarin content and a significant 12.28% increase in lignin content, while knockout mutant plants showed a 16.3% increase in total coumarin content and a 33.48% decrease in lignin content. Furthermore, 29,671 differentially expressed genes (DEGs) were obtained by comparative transcriptomics of OE-NAC20, KO-NAC20, and WT of ADF. A schematic diagram of the gene network interacting with AdNAC20 during the early-bolting process of ADF was constructed by DEG analysis. AdNAC20 was predicted to directly regulate the transcription of several genes with SNBE-like motifs in their promoter, such as MYB46, C3H, and CCoAOMT. In this study, AdNAC20 was shown to play a dual pathway function that positively enhanced lignin formation but negatively controlled coumarin formation. And the heterologous expression of the AdNAC20 gene at Arabidopsis thaliana proved that the AdNAC20 gene also plays an important role in the process of bolting and flowering.

Contribution of mitochondria to postmortem muscle tenderization: a review.

Postmortem meat tenderization is a process mediated by a series of biochemical reactions related to muscle cell death. Cell death is considered a sign that muscle has started to transform into meat. Mitochondria play a significant role in regulating and executing cell death, as they are an aggregation point for many cell death signals and are also the primary target organelle damaged by tissue anoxia. Mitochondrial damage is likely to have an expanded role in postmortem meat tenderization. This review presents current findings on mitochondrial damage induced by the accumulation of reactive oxygen species during postmortem anaerobic metabolism and on the impact of mitochondrial damage on proteolysis and discusses how this leads to improved tenderness during aging. The underlying mechanisms of mitochondrial regulation of postmortem muscle tenderization likely focus on the mitochondria's role in postmortem cell death and energy metabolism. The death process of postmortem skeletal muscle cells may exhibit multiple types, possibly involving transformation from autophagy to apoptosis and, ultimately, necroptosis or necrosis. Mitochondrial characteristics, especially membrane integrity and ATP-related compound levels, are closely related to the transformation of multiple types of dead postmortem muscle cells. Finally, a possible biochemical regulatory network in postmortem muscle tenderization is proposed.

COVID-19 and tinnitus: an initiative to improve tinnitus care.

OBJECTIVE: To investigate the effects of COVID-19 on individuals with tinnitus and their views to guide future tinnitus care. DESIGN: A mixed-methods cross-sectional research design. STUDY SAMPLE: An online survey was completed by 365 individuals with tinnitus from Australia and other countries. RESULTS: Tinnitus was reported to be more bothersome during the pandemic by 36% of respondents, whereas 59% reported no change and 5% reported less bothersome tinnitus. Nearly half of the respondents had received COVID-19 vaccination(s) and 12% of them reported more bothersome tinnitus while 2% developed tinnitus post-vaccination. Australian respondents spent less time in self-isolation or quarantine and saw fewer change in in-person social contact than respondents from other countries. More than 70% of respondents thought that tinnitus care services were insufficient both before and during the pandemic. Regarding their opinions on how to improve tinnitus care in the future, five themes including alleviation of condition, government policies, reduced barriers, self- and public-awareness, and hearing devices were identified. CONCLUSIONS: A majority of respondents did not perceive any change in tinnitus perception and one-third of respondents had worsened tinnitus during the pandemic. To improve tinnitus care, better awareness and more accessible resources and management are crucial.

Fully and partially exploratory factor analysis with bi-level Bayesian regularization.

This research introduces the fully and partially exploratory factor analysis (EFA) with bi-level Bayesian regularization. The proposed models enable factor selection with a sparse model by conceptualizing the factor and loading as the group and individual levels, respectively. They offer a series of benefits such as factor extraction and parameter estimation in one step, simultaneous estimation of the model and tuning parameters, and the availability of interval estimates. Moreover, partial knowledge can be incorporated together with unknown number of factors in the partially EFA. Simulation studies and real-data analyses demonstrated that both models performed satisfactorily under reasonable conditions and were robust to interference of local dependence, while the partially EFA with appropriate information can outperform the fully version and work well under more extreme conditions. The proposed models have been implemented in the R package LAWBL.

Self-reported Physical Activity and Cardiovascular Events in Adults With CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study.

RATIONALE & OBJECTIVE: In the general population, there is an association between higher levels of physical activity and lower risk for cardiovascular events and mortality, but this relationship has not been well evaluated in chronic kidney disease (CKD). We investigated the association between self-reported physical activity and outcomes in a CKD cohort. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,926 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Time-updated self-reported physical activity assessed by (1) quartile of moderate-to-vigorous physical activity (MVPA) and (2) meeting guideline-recommended level of physical activity (categorized as active, meeting guidelines; active, not meeting guidelines; or inactive). OUTCOME: Atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, and all-cause and cardiovascular death. ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: At baseline, compared with the lowest MVPA quartile, those in the highest quartile were more likely to be younger, male, not have prevalent cardiovascular disease, and have higher estimated glomerular filtration rate. Overall, 51% met the physical activity guidelines; of those who did not, 30% were inactive. During the median follow-up period of 13.4 years, there were 772 atherosclerotic events, 848 heart failure events, and 1,553 deaths, and 420 cardiovascular deaths. Compared with the participants in the lowest MVPA quartile, the highest quartile had a lower risk of atherosclerotic events (HR, 0.64 [95% CI, 0.51-0.79]), incident heart failure (HR, 0.71 [95% CI, 0.58-0.87]), and all-cause and cardiovascular death (HRs of 0.54 [95% CI, 0.46-0.63] and 0.47 [95% CI, 0.35-0.64], respectively). The findings were similar for analyses evaluating recommended level of physical activity. LIMITATIONS: Self-reported physical activity may result in some degree of misclassification. CONCLUSIONS: Higher self-reported physical activity was associated with lower risk of cardiovascular events and mortality in CKD patients, which may have important implications for clinical practice and the design of interventional studies. PLAIN-LANGUAGE SUMMARY: In this long-term study of 3,926 adults with chronic kidney disease, we found that individuals with higher levels of physical activity were less likely to experience an atherosclerotic event (for example, a heart attack, stroke, or peripheral arterial disease), new-onset heart failure, and death as compared with those with lower levels of physical activity. The findings were similar for the analyses evaluating adherence to guideline-recommended level of physical activity (that is, for more than 150 minutes per week), and they strengthen the evidence supporting the current guideline recommendations.

Perfusion and oxygenation in allografts with transplant renal artery stenosis: Evaluation with functional magnetic resonance imaging.

BACKGROUND: Transplant renal artery stenosis (TRAS) has been shown to reduce kidney perfusion leading to post-operative hypertension. We aimed to measure the perfusion and oxygenation changes in TRAS with arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging, respectively. METHODS: In this single-center prospective study, a total of seven patients with TRAS and seven age- and sex-matched normal kidney transplant recipients underwent both ASL and BOLD imaging. Moreover, measurements of ASL and BOLD were also performed in five patients after successful angioplasty for TRAS. RESULTS: Allograft cortical perfusion as measured by ASL in the TRAS group was significantly decreased as compared with normal control group (129.9 ± 46.6 ml/100 g vs. 202.4 ± 47.7 ml/100 g, P = .01). Interestingly, allograft oxygenation as indicated by R2* derived from BOLD in both the cortex (16.42 ± 1.90 Hz vs. 18.25 ± 4.34 Hz, P = .33) and the medulla (30.34 ± 2.35 Hz vs. 30.43 ± 6.85 Hz, P = .97) showed no statistical difference between the TRAS and normal control group. In addition, both cortical and medullary oxygenation remained unchanged despite significantly improved cortical perfusion in those undergone successful angioplasty. CONCLUSION: Cortical and medullary oxygenation were preserved in the presence of reduced allograft perfusion in clinically significant TRAS. Prospective larger studies are needed to conclusively establish perfusion and oxygenation changes in TRAS.

Developmental disparities in sedentary time by period of the day among US youth: a cross-sectional study.

BACKGROUND: Definitive evidence shows sedentary time (ST) is an independent risk factor for chronic disease, irrespective of physical activity. Despite calls to limit youth ST, studies demonstrate a spike in ST at the transition from childhood to adolescence. Identifying periods of the day (e.g., before school, during school, afterschool, and evenings) during which ST is higher in adolescents vs. children-that is, specifying when within daily routines ST disparities emerge-may be important to inform intervention strategies, as periods of the day correspond with variations in setting and supervision. The purpose of this study was to examine device-assessed ST engagement by period of day and developmental stage in a nationally representative sample of United States youth. METHODS: Youth (N = 2,972 between 6-18 years) from the 2003-2004 and 2005-2006 waves of NHANES reported demographic variables and wore an accelerometer for seven consecutive days to determine ST. Linear regression analyses were applied to study associations between ST and developmental stage (childhood or adolescence) by period of the week and weekend days, while controlling for sex, race/ethnicity, annual family income, and body mass index. RESULTS: Adjusted linear regressions (p-values < 0.0001) showed that adolescents were more sedentary than children during school, afterschool, and weekday evening periods as well as all the weekend periods. However, during school (36.3 ± 7.3 vs. 28.2 ± 7.2 min/hour; b = -7.4 [-8.1, -6.6]) and afterschool periods (31.1 ± 7.7 vs. 22.7 ± 7.0 min/hour; b = -7.8 [-8.6, -7.0]) showed the largest weekly ST disparities by developmental stage. Overall, the during school and after school hours constitute most (during school = 35% and afterschool = 16%) of the weekly ST disparity between children and adolescents. CONCLUSIONS: Our data provide interventionists with estimates of the potential for ST reduction in each setting and period of the day among US adolescents. Future research should gather information about the barriers and facilitators of ST in adolescents by period of the day to help understand factors driving disparities.

Resveratrol protects against ox-LDL-induced endothelial dysfunction in atherosclerosis via depending on circ_0091822/miR-106b-5p-mediated upregulation of TLR4.

BACKGROUND: Atherosclerosis (AS) is the most common inducer of cardiovascular diseases, and resveratrol (RSV) has played a protective function in the endothelial injury of AS. This study was to explore the molecular mechanism of RSV in oxidized low-density lipoprotein (ox-LDL)-mediated endothelial dysfunction. METHODS: Circ_0091822, microRNA-106b-5p (miR-106b-5p) or toll-like receptor (TLR4) levels were examined using reverse transcription-quantitative polymerase chain reaction assay. Cell viability was detected via Cell Counting Kit-8 assay and angiogenesis was assessed by tube formation assay. Cell apoptosis was determined through flow cytometry. The protein analysis was conducted via western blot. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The oxidative injury was evaluated using the commercial kits. The binding detection was performed via dual-luciferase reporter assay and RNA pull-down assay. RESULTS: Circ_0091822 was downregulated by RSV in ox-LDL-treated endothelial cells. RSV promoted cell viability and angiogenesis while inhibiting apoptosis, inflammation, and oxidative stress after exposure to ox-LDL. The circ_0091822 knockdown relieved the ox-LDL-induced cell damages. RSV suppressed the ox-LDL-caused endothelial dysfunction via inducing the downregulation of circ_0091822. Circ_0091822 could target miR-106b-5p, and the reversal of circ_0091822 for RSV function was achieved by sponging miR-106b-5p. Circ_0091822 absorbed miR-106b-5p to elevate the level of TLR4. RSV impeded ox-LDL-induced damages by regulating miR-106b-5p/TLR4 axis. CONCLUSION: All these findings suggested that RSV acted as an inhibitory factor in ox-LDL-induced endothelial injury via downregulating circ_0091822 to upregulate miR-106b-5p-related TLR4.

A Generalized Partially Confirmatory Factor Analysis Framework with Mixed Bayesian Lasso Methods.

This research extends the partially confirmatory approach to accommodate mixed types of data and missingness in a unified framework that can address a wide range of the confirmatory-exploratory continuum in factor analysis. A mix of Bayesian adaptive and covariance Lasso procedures was developed to estimate model parameters and regularize the loading structure and local dependence simultaneously. Several model variants were offered with different constraints for identification. The less-constrained variant can achieve sufficient condition for the more-powerful variant, although loading estimates associated with local dependence can be inflated. Parameter recovery was satisfactory, but the information on local dependence was partially lost with categorical data or missingness. A real-life example illustrated how the models can be used to obtain a more discernible loading pattern and to identify items that do not measure what they are supposed to measure. The proposed methodology has been implemented in the R package LAWBL.

High Strength and Low Coercivity of Cobalt with Three-Dimensional Nanoscale Stacking Faults.

Lower coercivity (HC) and magnetic anisotropy (K1) coupled with high mechanical strength are essential properties for Co-based soft magnetic thin films; however, the strength-coercivity trade-off limits their development. Co with face centered cubic structure (fcc) exhibits lower HC and K1 than its grand hexagonal close packed structure (hcp); however, metastable fcc-phase Co is hard to stabilize. Here, by using Cu (100) seed layer, we synthesized micron-thick fcc Co films with self-formed three-dimensional nanoscale stacking faults (3D-nSFs) that could achieve high strengths without sacrificing soft magnetic properties. The 3D-nSFs, induced by the Co/Cu interface, could not only stabilize the metastable fcc Co to yield lower HC but also impede dislocation motion to strengthen Co films. More importantly, we successfully tailored the density of 3D-nSFs and confirmed a large variation in magnetic coercivity (by 100%) and indentation hardness (by 25%). This work provides a new strategy for integrated performance optimization by interface design and strain engineering.

Focal Segmental Glomerulosclerosis Superimposed on Transplant Glomerulopathy: Implications for Graft Survival.

INTRODUCTION: Transplant glomerulopathy (TG) is a morphological lesion resulting from chronic glomerular endothelium injury, and it is strongly associated with poor graft survival. TG coexisting with focal segmental glomerulosclerosis (FSGS) can be found in renal allograft biopsies, but few related studies are available. METHODS: Consecutive kidney transplant recipients with biopsy-proven TG were studied retrospectively. Patients concomitant with FSGS were identified and compared with those without FSGS. The influence of FSGS on allograft outcomes was assessed using univariate and multivariate Cox regression models. RESULTS: Of the 66 patients with TG, 40 (60.6%) had concomitant FSGS. TG patients with FSGS had higher proteinuria (median, 2.6 vs. 0.8 g/24 h, p < 0.001) and serum creatinine levels (median, 2.5 vs. 2.1 mg/dL, p = 0.04), lower serum albumin levels, higher chronic glomerulopathy (cg) score, larger glomerular tuft area, lower number of podocytes, and higher incidences of podocyte hyperplasia, pseudotubule formation, and diffuse foot process effacement than those without FSGS (all p < 0.05). The kidney allograft loss rate of patients with FSGS was higher than that of patients without FSGS (65.7% vs. 37.5%, p = 0.03). The presence of FSGS was independently associated with allograft loss in TG (hazard ratio (HR) = 3.42, 95% confidence interval (CI): 1.30-8.98, p = 0.01). Other independent predictors were proteinuria (HR = 1.18, 95% CI: 1.02-1.37, p = 0.02), estimated glomerular filtration rate (HR = 0.94, 95% CI: 0.91-0.97, p < 0.001), and panel reactive antibody (HR = 3.99, 95% CI: 1.14-13.99, p = 0.03). Moreover, FSGS (odds ratio (OR) = 4.39, 95% CI: 1.29-14.92, p = 0.02) and cg (OR = 5.36, 95% CI: 1.56-18.40, p = 0.01) were independent risk factors for proteinuria. CONCLUSION: In this cohort of patients with TG, the presence of FSGS was strongly associated with more severe clinicopathological features and worse allograft survival.

Early detection of subclinical pathology in patients with stable kidney graft function by arterial spin labeling.

OBJECTIVES: To evaluate the utility of arterial spin labeling (ASL) for the identification of kidney allografts with underlying pathologies, particularly those with stable graft function. METHODS: A total of 75 patients, including 18 stable grafts with normal histology (normal group), 21 stable grafts with biopsy-proven pathology (subclinical pathology group), and 36 with unstable graft function (unstable graft group), were prospectively examined by ASL magnetic resonance imaging. Receiver operating characteristic curves were generated to calculate the area under the curve (AUC), sensitivity, and specificity. RESULTS: Patient demographics among the 3 groups were comparable. Compared with the normal group, kidney allograft cortical ASL values decreased in the subclinical pathology group and the unstable graft group (204.7 ± 44.9 ml/min/100 g vs 152.5 ± 38.9 ml/min/100 g vs 92.3 ± 37.4 ml/min/100 g, p < 0.001). The AUC, sensitivity, and specificity for discriminating allografts with pathologic changes from normal allografts were 0.92 (95% CI, 0.83-0.97), 71.9%, and 100% respectively by cortical ASL and 0.82 (95% CI, 0.72-0.90), 54.4%, and 100% respectively by serum creatinine. The cortical ASL identified allografts with subclinical pathology among patients with stable graft function with an AUC of 0.80 (95% CI, 0.64-0.91), sensitivity of 57.1%, and specificity of 88.9%. Combined use of proteinuria and cortical ASL could improve the sensitivity and specificity to 76.2% and 100% respectively for distinguishing the subclinical pathology group from the normal group. CONCLUSIONS: Cortical ASL is useful for the identification of allografts with underlying pathologies. More importantly, ASL showed promise as a non-invasive tool for the clinical translation of identifying kidney allografts with subclinical pathology. KEY POINTS: • Cortical ASL values were decreased in kidney allografts with subclinical pathologic changes as compared with normal allografts (152.5 ± 38.9 ml/min/100 g vs 204.7 ± 44.9 ml/min/100 g, p < 0.001). • Cortical ASL differentiated allografts with pathologic changes and subclinical pathology group from normal group with an AUC of 0.92 (95% CI, 0.83-0.97) and 0.80 (95% CI, 0.64-0.91) respectively. • Cortical ASL discriminated allografts with underlying pathologic changes from normal allografts with a specificity of 100%, and combined use of proteinuria and cortical ASL values could also achieve 100% specificity for discriminating allografts with subclinical pathology from normal allografts.

Real-world unassisted quit success and related contextual factors: a population-based study of Chinese male smokers.

OBJECTIVES: To examine the association of exposure to secondhand smoke (SHS) and tobacco advertising with unassisted smoking cessation among Chinese male smokers. METHODS: A questionnaire was administered to 6500 male adult smokers from six cities in China selected in a cross-sectional multistage sampling design. The survey collected self-reported demographic characteristics, smoking and cessation status, SHS exposure and tobacco advertising exposure, with 5782 valid questionnaires included in this study. Multiple logistic regression analysis was used to assess the association of unassisted smoking cessation with exposure to SHS and tobacco advertising. RESULTS: 42.1% of smokers who made unassisted quit attempts achieved abstinence (95% CI 32.5% to 51.7%). SHS (adjusted OR (aOR) 0.36; 95% CI 0.18 to 0.71; p=0.033) and tobacco advertising exposure (aOR 0.63; 95% CI 0.37 to 0.95; p=0.039) were negatively associated with unassisted smoking cessation. CONCLUSION: The vast majority of Chinese male smokers rely on unassisted methods to quit smoking. Success prevalence is high, which is very beneficial to health. This study suggests that exposure to secondhand smoking and tobacco advertising hinders the success of unassisted cessation. These findings speak to the need for environmental tobacco control measures to promote unassisted smoking cessation among Chinese adult male smokers.

Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China.

BACKGROUND: Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis. METHODS: Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared. RESULTS: After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR. CONCLUSIONS: Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding.

Incident Chronic Kidney Disease Risk among Hispanics/Latinos in the United States: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Although Hispanics/Latinos in the United States are often considered a single ethnic group, they represent a heterogenous mixture of ancestries who can self-identify as any race defined by the U.S. Census. They have higher ESKD incidence compared with non-Hispanics, but little is known about the CKD incidence in this population. METHODS: We examined rates and risk factors of new-onset CKD using data from 8774 adults in the Hispanic Community Health Study/Study of Latinos. Incident CKD was defined as eGFR <60 ml/min per 1.73 m2 with eGFR decline ≥1 ml/min per 1.73 m2 per year, or urine albumin/creatinine ratio ≥30 mg/g. Rates and incidence rate ratios were estimated using Poisson regression with robust variance while accounting for the study's complex design. RESULTS: Mean age was 40.3 years at baseline and 51.6% were women. In 5.9 years of follow-up, 648 participants developed CKD (10.6 per 1000 person-years). The age- and sex-adjusted incidence rates ranged from 6.6 (other Hispanic/mixed background) to 15.0 (Puerto Ricans) per 1000 person-years. Compared with Mexican background, Puerto Rican background was associated with 79% increased risk for incident CKD (incidence rate ratios, 1.79; 95% confidence interval, 1.33 to 2.40), which was accounted for by differences in sociodemographics, acculturation, and clinical characteristics. In multivariable regression analysis, predictors of incident CKD included BP >140/90 mm Hg, higher glycated hemoglobin, lower baseline eGFR, and higher baseline urine albumin/creatinine ratio. CONCLUSIONS: CKD incidence varies by Hispanic/Latino heritage and this disparity may be in part attributed to differences in sociodemographic characteristics. Culturally tailored public heath interventions focusing on the prevention and control of risk factors might ameliorate the CKD burden in this population.

[Bioinformatics analysis and expression pattern of NAC transcription factor family of Angelica dahurica var. formosana from Sichuan province].

NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.