Dynamic statistical model for predicting the risk of death among older Chinese people, using longitudinal repeated measures of the frailty index: a prospective cohort study.

BACKGROUND: Frailty is a common characteristic of older people with the ageing process. We aimed to develop and validate a dynamic statistical prediction model to calculate the risk of death in people aged ≥65 years, using a longitudinal frailty index (FI). METHODS: One training dataset and three validation datasets from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were used in our study. The training dataset and validation datasets 1 to 3 included data from 9,748, 7,459, 9,093 and 6,368 individuals, respectively. We used 35 health deficits to construct the FI and a longitudinal FI based on repeated measurement of FI at every wave of the CLHLS. A joint model was used to build a dynamic prediction model considering both baseline covariates and the longitudinal FI. Areas under time-dependent receiver operating characteristic curves (AUCs) and calibration curves were employed to assess the predictive performance of the model. RESULTS: A linear mixed-effects model used time, sex, residence (city, town, or rural), living alone, smoking and alcohol consumption to calculate a subject-specific longitudinal FI. The dynamic prediction model was built using the longitudinal FI, age, residence, sex and an FI-age interaction term. The AUCs ranged from 0.64 to 0.84, and both the AUCs and the calibration curves showed good predictive ability. CONCLUSIONS: We developed a dynamic prediction model that was able to update predictions of the risk of death as updated measurements of FI became available. This model could be used to estimate the risk of death in individuals aged >65 years.

Hippocampal atrophy and functional connectivity disruption in cirrhotic patients with minimal hepatic encephalopathy.

The hippocampus is a crucial pathological node for minimal hepatic encephalopathy (MHE) and it is associated with various cognitive impairments. Investigations on alterations involving hippocampal morphology and functional connectivity (FC) in MHE are limited. This study aimed to simultaneously evaluate hippocampal volume and FC alterations and their association with cognitive decline in MHE. Twenty-two cirrhotic patients with MHE, 31 cirrhotic patients without MHE (NHE), and 43 healthy controls underwent high-resolution T1-weighted imaging, resting-state functional magnetic resonance imaging, and cognition assessment based on Psychometric Hepatic Encephalopathy Score (PHES). The structural images were preprocessed using a voxel-based morphometry method, during which hippocampal volume was measured. The hippocampal connectivity network was identified using seed-based correlation analysis. Hippocampal volume and FC strength were compared across the three groups and correlated against the PHES results of the cirrhotic patients. Compared to the controls, MHE patients exhibited a significantly lower bilateral hippocampal volume. A slight decrease in hippocampal volume was obtained from NHE to MHE, but it did not reach statistically significance. In addition, the average FC strength of the bilateral hippocampal connectivity network was significantly lower in the MHE patients. In particular, the MHE patients showed a decrease in FC involving the left hippocampus to bilateral posterior cingulate gyrus and left angular gyrus. The MHE patients also showed FC reduction between the right hippocampus and bilateral medial frontal cortex. A progressive reduction in hippocampal FC from NHE to MHE was also observed. The bilateral hippocampal FC strength (but not hippocampal volume) was positively correlated with the PHES results of the cirrhotic patients. Our assessment of MHE patients revealed decreased hippocampal volume, which suggests regional atrophy, and reduced hippocampal connectivity with regions that are primarily involved in the default-mode network, thereby suggesting a functional disconnection syndrome. These alterations reveal the mechanisms underlying cognitive deterioration with disease progression.

Sleep duration and sleep disturbances in association with falls among the middle-aged and older adults in China: a population-based nationwide study.

BACKGROUND: Falls pose major health problems to the middle-aged and older adults and may potentially lead to various levels of injuries. Sleep duration and disturbances have been shown to be associated with falls in literature; however, studies of the joint and distinct effects of those sleep problems are still sparse. To fill this gap, we aimed to determine the association between sleep duration, sleep disturbances and falls among middle-aged and older adults in China controlling for psychosocial, lifestyle, socio-demographical factors and comorbidity. METHODS: Data were derived from the China Health and Retirement Longitudinal Study (CHARLS) based on multi-stage sampling designs, with respondents aged 50 and older. Associations were evaluated by using multiple logistic regression adjusting for confounders and complex survey design. To further determine if the association of sleep duration/disturbance and falls depends on age groups, the study data were divided into two samples (age 50-64 vs. age 65+) and comparison was made between the two age groups. RESULTS: Of the 12,759 respondents, 2172 (17%) had falls within the last 2 years. Our findings indicated that the participants who had nighttime sleep duration ≤5 were more likely to report falls than those who had nighttime sleep duration ≥6 h; whereas no association between nighttime sleep duration > 8 h and falls. Participants having sleep disturbances 1-2 days, or 3-4 days, and 5-7 days per week were also more likely to report falls than those who had no sleep disturbance. The nap sleep duration was not significantly associated with falls. Although the combined sample found both sleep duration and sleep disturbance to be strongly associated with falls after adjusting for various confounders, sleep disturbance was not significantly related to falls among participants aged 65 + . CONCLUSIONS: Our study suggested that there is an independent association between falls and short sleep duration and disturbed sleep among middle-aged and older adults in China. Findings underscore the need for evidence-based prevention and interventions targeting sleep duration and disturbance among this study population.

Cystatin C is Associated With Plaque Phenotype and Plaque Burden.

BACKGROUND/AIMS: The relationship between carotid artery plaque burden, phenotype and serum cystatin C at normal and impaired renal function is still unclear. METHODS: Demographic characteristics, carotid ultrasonography and other relevant information of 1,477 patients were collected. The association of carotid artery plaque burden, plaque phenotype with serum cystatin C was evaluated by strategy analysis based on renal function. RESULTS: Serum cystatin C (OR=2.05, 95% CI: 1.83-2.29, P<.01) was a risk factor of stable plaque among patients with normal glomerular filtration rate. However, in the patients with mild impaired renal function, serum cystatin C was not only a risk factor for stable plaque (OR=1.60, 95% CI: 1.43-1.78, P<.001) but also was a risk factor for unstable plaque (OR=1.21, 95% CI: 1.10-1.32, P<.001). The smoothing function curve and a three-piecewise linear regression revealed that a nonlinear relationship was observed between serum cystatin C and plaque burden. When serum cystatin C was in the range of 0.75-1.30 (mg/L), the plaque burden tended to increase. CONCLUSION: In normal renal function, serum cystatin C may confer stability of plaques. In mildly impaired renal function, serum cystatin C is a risk predictor of plaques. In normal renal function circumstances, serum cystatin C may benefit to the stability of plaques. In mild impaired renal function circumstances, serum cystatin C are a risk predictors of plaques.

MicroRNAs as potential diagnostic biomarkers in renal cell carcinoma.

Emerging evidence has suggested that microRNAs (miRNAs) may be promising novel biomarkers for the diagnosis of renal cell carcinoma (RCC). However, the results of current studies are still conflicting. Hence, we undertake the current meta-analysis to comprehensively assess the diagnostic potential of miRNAs in RCC. The bivariate meta-analysis model was employed to summarize the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curve and area under the curve (AUC) were used to evaluate the diagnostic accuracy. Subgroup analyses and meta-regression were used to explore the between-study heterogeneity. Deeks' funnel plot asymmetry test was used to test the potential of publication bias. All analyses were performed using STATA software (version 12.0). The pooled sensitivity and specificity of miRNAs for the diagnosis of RCC were 0.85 (95% confidence interval (CI), 0.77-0.90) and 0.84 (95% CI, 0.70-0.92). The value of AUC was 0.91 (95% CI, 0.88-0.93), suggesting that the diagnostic accuracy of miRNAs achieved a relatively high level. Furthermore, subgroup analyses showed that tissue-based miRNA assay is recommended to improve the diagnostic accuracy. In conclusion, the high degree of diagnostic accuracy suggests that miRNA in RCC patients may serve as next-generation biomarkers for detection of the disease. However, large-scale investigations and additional improvements are urgently needed to confirm our results and verify the feasibility of routine clinical utilization.

Phenacetin promoted the rapid start-up and stable maintenance of partial nitrification: Responses of nitrifiers and antibiotic resistance genes.

Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its potential microbial mechanism was still unclear. In this study, PN could be initiated within six days by PNCT anaerobic soaking treatment (8 mg/L). In order to improve the stable performance of PN, 21 times of PNCT aerobic soaking treatment every three days was conducted and PN was stabilized for 191 days. After PN was damaged, ten times of PNCT aerobic soaking treatment every three days was conducted and PN was recovered after once soaking, maintained over 88 days. Ammonia oxidizing bacteria might change the dominant oligotype to gradually adjust to PNCT, and the increase of abundance and activity of Nitrosomonas promoted the initiation of PN. For nitrite-oxidizing bacteria (NOB), the increase of Candidatus Nitrotoga and Nitrospira destroyed PN, but PN could be recovered after once aerobic soaking illustrating NOB was not resistant to PNCT. KEGG and COG analysis suggested PNCT might disrupt rTCA cycle of Nitrospira, resulting in the decrease of relative abundance of Nitrospira. Moreover, PNCT did not lead to the sharp increase of absolute abundances of antibiotic resistance genes (ARGs), and the risk of ARGs transmission was negligible.

Solvent-free enzymatic synthesis of 1, 3-diacylglycerols by direct esterification of glycerol with saturated fatty acids.

BACKGROUND: Pure 1, 3-diacylglycerols (1, 3-DAG) have been considered to be significant surfactants in food, cosmetics and pharmaceutical industries, as well as the effect on obesity prevention. METHODS: In this study, a vacuum-driven air bubbling operation mode was developed and evaluated for the enzymatic synthesis of 1, 3-DAG of saturated fatty acids, by direct esterification of glycerol with fatty acids in a solvent-free system. The employed vacuum-driven air bubbling operation mode was comparable to vacuum-driven N2 bubbling protocol, in terms of lauric acid conversion and 1, 3-dilaurin content. RESULTS: Some operation parameters were optimized, and 95.3% of lauric acid conversion and 80.3% of 1, 3-dilaurin content was obtained after 3-h reaction at 50°C, with 5 wt% of Lipozyme RM IM (based on reactants) amount. Of the lipases studied, both Lipozyme RM IM and Novozym 435 exhibited good performance in terms of lauric acid conversion. Lipozyme TL IM, however, showed low activity. Lipozyme RM IM showed good operational stability in this operation protocol, 80.2% of the original catalytic activity remained after 10 consecutive batch applications. Some other 1, 3-DAG were prepared and high content was obtained after purification: 98.5% for 1, 3-dicaprylin, 99.2% for 1, 3-dicaprin, 99.1% for 1, 3-dilaurin, 99.5 for 1, 3-dipalmitin and 99.4% for 1, 3-disterin. CONCLUSION: The established vacuum-driven air bubbling operation protocol had been demonstrated to be a simple-operating, cost-effective, application practical and efficient methodology for 1, 3-DAG preparation.

The knock-on effects of different wastewater feeding modes: Change in microbial communities versus resistance genes in pilot-scale aerobic sludge granulation reactors.

To explore the effects of wastewater feeding modes on the formation of aerobic granular sludge (AGS) and the complex relationships between resistance genes and bacteria, two pilot-scale sequencing batch reactors (SBRs) were established. The SBR with influent wastewater introduced uniformly through pipes at bottom was designated as BSBR, and the SBR with inlet wastewater flowing directly from top was TSBR. BSBR formed dense AGS due to uniform wastewater feeding at bottom, while TSBR failed to cultivate AGS. Metagenomic sequencing illustrated that rapid growth of AGS in BSBR was accompanied with increase of antibiotic resistance genes (ARGs) abundance, but ARGs diminished when the size of AGS was stable. The ARGs continued to elevate in TSBR, and abundance of metal resistance genes (MRGs) was always higher than that in BSBR. Two reactors had markedly different bacterial community, microbes in BSBR owned stronger activity, conferred greater potential to proliferate. AdeF in two systems had the most complex gene-bacteria relationships which would undergo HGT within bacterial genus. The different feeding modes of wastewater directly led to the changing size of sludge, which caused knock-on effects of variations in the abundance of microbial communities and resistance genes. This study provided promising suggestions for the rapid cultivation of AGS and control of resistance genes at pilot-scale.

Molecular diagnosis of putative Stargardt Disease probands by exome sequencing.

BACKGROUND: The commonest genetic form of juvenile or early adult onset macular degeneration is Stargardt Disease (STGD) caused by recessive mutations in the gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but non-trivial amount of locus heterogeneity currently impede conclusive molecular diagnosis in a significant proportion of cases. METHODS: We performed whole exome sequencing (WES) of nine putative Stargardt Disease probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Follow-up dideoxy sequencing was performed for confirmation and to screen for mutations in an additional set of affected individuals lacking a definitive molecular diagnosis. RESULTS: Whole exome sequencing revealed seven likely disease-causing variants across four genes, providing a confident genetic diagnosis in six previously uncharacterized participants. We identified four previously missed mutations in ABCA4 across three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1 were also identified. CONCLUSIONS: Our findings highlight the enormous potential of whole exome sequencing in Stargardt Disease molecular diagnosis and research. WES adequately assayed all coding sequences and canonical splice sites of ABCA4 in this study. Additionally, WES enables the identification of disease-related alleles in other genes. This work highlights the importance of collecting parental genetic material for WES testing as the current knowledge of human genome variation limits the determination of causality between identified variants and disease. While larger sample sizes are required to establish the precision and accuracy of this type of testing, this study supports WES for inherited early onset macular degeneration disorders as an alternative to standard mutation screening techniques.

Identification of serum glycobiomarkers for Hepatocellular Carcinoma using lectin microarrays.

Objective: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer and ranks third in mortality among all malignant tumors; as a result, HCC represents a major human health issue. Although aberrant glycosylation is clearly implicated in HCC, changes in serum immunoglobulin (Ig)G and IgM glycosylation have not been comprehensively characterized. In this study, we used lectin microarrays to evaluate differences in serum IgG and IgM glycosylation among patients with HCC, hepatitis B cirrhosis (HBC), or chronic hepatitis B (CHB), and healthy normal controls (NC) and aimed to establish a model to improve the diagnostic accuracy of HCC. Methods: In total, 207 serum samples collected in 2019-2020 were used for lectin microarray analyses, including 97 cases of HCC, 50 cases of HBC, 30 cases of CHB, and 30 cases of NC. Samples were randomly divided into training and validation groups at a 2:1 ratio. Training group data were used to investigate the diagnostic value of the relative signal intensity for the lectin probe combined with alpha-fetoprotein (AFP). The efficacy of models for HCC diagnosis were analyzed by receiver operating characteristic (ROC) curves. Results: In terms of IgG, a model combining three lectins and AFP had good diagnostic accuracy for HCC. The area under the ROC curve was 0.96 (P < 0.05), the sensitivity was 82.54%, and the specificity was 100%. In terms of IgM, a model including one lectin combined with AFP had an area under the curve of 0.90 (P < 0.05), sensitivity of 75.41%, and specificity of 100%. Conclusion: Estimation of serum IgG and IgM glycosylation could act as complementary techniques to improve diagnosis and shed light on the occurrence and development of the HCC.

Safety of SGLT2 Inhibitors: A Pharmacovigilance Study from 2013 to 2021 Based on FAERS.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are widely used in clinical practice for their demonstrated cardiorenal benefits, but multiple adverse events (AEs) have been reported. We aimed to describe the distribution of SGLT2i-related AEs in different systems and identify important medical event (IME) signals for SGLT2i. Methods: Data from the first quarter (Q1) of 2013-2021 Q2 in FAERS were selected to conduct disproportionality analysis. The definition of AEs and IMEs relied on the system organ classes (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA-version 24.0). Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to estimate the association between SGLT2is and IMEs. Results: A total of 57,818 records related to SGLT2i, with 22,537 SGLT2i-IME pairs. Most SGLT2i-related IMEs occurred in monotherapy (N = 21,408, 94.99%). Significant signals emerged at the following SOCs: "metabolism and nutrition disorders" (N = 9,103; IC025 = 4.26), "renal and urinary disorders" (3886; 1.20), "infections and infestations" (3457; 0.85). The common strong signals were observed in diabetic ketoacidosis, ketoacidosis, euglycaemic diabetic ketoacidosis and Fournier's gangrene. Unexpected safety signals such as cellulitis, osteomyelitis, cerebral infarction and nephrolithiasis were detected. Conclusion: Our pharmacovigilance analysis showed that a high frequency was reported for IMEs triggered by SGLT2i monotherapy. Different SGLT2is caused different types and the association strengths of IMEs, while they also shared some specific PTs. Most of the results are generally consistent with previous studies, and more pharmacoepidemiological studies are needed to validate for unexpected AEs. Based on risk-benefit considerations, clinicians should be well informed about important medical events that may be aggravated by SGLT2is.

Evaluation of a kindergarten-based nutrition education intervention for pre-school children in China.

OBJECTIVE: To evaluate the impact of nutrition education in kindergartens and to promote healthy dietary habits in children. DESIGN: Prospective cohort study. Four kindergartens with 1252 children were randomized to the intervention group and three with 850 children to the control group. The personal nutritional knowledge, attitudes and dietary behaviours of the parents were also investigated. Each month, children and parents in the intervention group participated in nutrition education activities. The main outcome measures were anthropometrics and diet-related behaviours of the children and the nutritional knowledge and attitudes of the parents at baseline, 6 months (mid-term) and 1 year (post-test). Baseline demographic and socio-economic characteristics were also collected. SETTING: Seven kindergartens from Hefei, the capital city of Anhui Province, eastern China. SUBJECTS: Two thousand one hundred and two 4- to 6-year-old pre-schoolers from seven kindergartens participated. RESULTS: The prevalence of children's unhealthy diet-related behaviours decreased significantly and good lifestyle behaviours increased in the group receiving nutrition education compared with controls. Parental eating habits and attitudes to planning their children's diets also changed appreciably in the intervention group compared with the control group (P < 0.05). However, there were no statistically significant differences in children's height, weight, height-for-age Z-score or weight-for-age Z-score between the two groups. CONCLUSIONS: Kindergarten-based nutrition education improves pre-schoolers' lifestyle behaviours and brings about beneficial changes in parents' attitudes to planning their children's diets and their own personal eating habits.

Using excess sludge as carbon source for enhanced nitrogen removal and sludge reduction with hydrolysis technology.

In order to improve the nitrogen removal efficiency and to achieve the sludge reduction in traditional wastewater treatment plants, a combined hydrolysis-anoxic-oxic (H-A-O) pilot-scaled reactor was used in this study to investigate the possibility and validity of using excess activated sludge (EAS) fermentation liquids to enhance the nitrogen removal. The results clearly showed that sludge acidification rate in fermentation reactor can reach to 43.2%. The percentages of acetic acid, propionic acid and butyric acid in the fermentation liquids were 68.4, 25.3 and 6.3%, respectively, while those in domestic wastewater were 73.0, 12.2 and 13.8%, respectively. Bioavailability of soluble chemical oxygen demand (SCOD) from fermentation liquids and domestic wastewater were investigated in batch reactors with nitrate as the electron accepter as well. The corresponding specific denitrification rates were 0.15 g NO3⁻-N/g VSS d⁻¹ and 0.09 g NO3⁻-N/g VSS d⁻¹. When the substances were enough, the denitrification reaction appeared to follow the zero-order kinetics. The results also showed that, when the H-A-O pilot-scaled reactor was operated continuously and sludge fermentation liquids were applied as additional carbon source in the A-O reactor, the removal efficiencies of SCOD, NH4+-N and total nitrogen (TN) were higher than 90, 95 and 79%, respectively. EAS reduction rate in this system was able to reach 40.4%, and the sludge VSS/SS ratio decreased from 0.82 to 0.59 after hydrolysis step.

Successful granulation and microbial differentiation of activated sludge in anaerobic/anoxic/aerobic (A2O) reactor with two-zone sedimentation tank treating municipal sewage.

A continuous pilot-scale A2O reactor with a two-zone sedimentation tank (A2O-TST) was constructed for the formation of aerobic granular sludge (AGS) to treat real municipal sewage. The characteristics of sludge, nutrient removal performance and the corresponding microbial ecology dynamics were studied during granulation process. Experimental results indicated that AGS with a mean particle size of 210 µm and sludge volume index after 30 min of 47.5 mL/g was successfully formed with effluent COD, total nitrogen and total phosphorus concentrations in the reactor reaching 22.8, 3.5 and 0.2 mg/L, respectively. Furthermore, high throughput data indicated that granules in settling tank-1 (ST-1) harbored slow-growing autotrophic organisms like Nitrosomonas and Nitrospira, while the flocs in settling tank-2 (ST-2) were dominated by fast-growing heterotrophic organisms including Ca. Accumulibacter, Dechloromonas, Flavobacterium, Arcobacter and Halomonas. Simulation results using computational fluid dynamics and discrete element method (CFD-DEM) modeling verified that the selection pressure created by the TST separator contributed to the retention of heavy granules (>1.011 kg/m3 density) in ST-1 zone and the withdrawal of light flocs (<1.011 kg/m3 density) from ST-2 zone. Therefore, the segregation of biomass using the TST system provides an opportunity to select for desired microbial populations and to optimize the nitrogen and phosphorus removal performance of the A2O-TST reactor. This study could add a guiding sight into the application of two-sludge system based on AGS technology for upgrading traditional A2O process.

Emergence and spread patterns of antibiotic resistance genes during two different aerobic granular sludge cultivation processes.

The prevalence and accumulation of antibiotic resistance genes (ARGs) were frequently detected in biological wastewater treatment processes, which might cause potential health crisis to human. In present study, the fates of ARGs during two different aerobic granular sludge (AGS) cultivation processes were investigated. The results showed that traditional AGS (T-AGS) cultivation process and enhanced AGS (E-AGS) cultivation process had significant differences (P < 0.005) in ARGs shift patterns. E-AGS process had higher average relative abundance (0.280 ± 0.079) of ARGs than T-AGS process (0.130 ± 0.041), while the intensity of ARGs enrichment during E-AGS (1.52-5.29 fold) was lower than T-AGS (3.79-75.31 fold) process. TnpA and intI1 as two different types of mobile genetic elements (MGEs) carrying ARGs, were observed to contribute significantly to the horizontal gene transfer (HGT) during T-AGS (r = 0.902, P < 0.050) and E-AGS (r = 0.823, P < 0.001) processes, respectively. Higher HGT level took place and more possible potential hosts (25 hosts) harboring ARGs were detected during E-AGS process comparing with T-AGS process (17 hosts). Meanwhile, over large AGS might increase the propagation of several antibiotic deactivation ARGs, so it was not advised. Overall, whether during T-AGS or during E-AGS process which was applied in a pilot-scale sequencing batch reactor treating municipal wastewater, the accumulation and spread of ARGs were inevitable. It should be valued that some suitable pre-treatments of seed sludge should be executed, meanwhile, advanced treatment for removing of ARGs in AGS should be conducted to maintain the relative abundances of ARGs at relatively low level.

Enhanced granulation process, a more effective way of aerobic granular sludge cultivation in pilot-scale application comparing to normal granulation process: From the perspective of microbial insights.

Aerobic granular sludge (AGS) could be cultivated from only flocs (called normal granulation (NG) process) or mixture of flocs and crushed AGS (called enhanced granulation (EG) process), which might lead to different system performances such as granulation speed and pollutants removal efficiencies. However, the differences of mechanisms between NG and EG processes at microbial community level are still unknown. In this study, the NG and EG processes were implemented successively in a pilot-scale sequencing batch reactor (SBR) with certain amounts of additional carbon sources. Illumina MiSeq sequencing and quantitative PCR were applied to investigate the dynamics of bacterial communities during NG and EG processes and explore the possible explanations for faster EG process. The results showed that significant distinctions in bacterial diversities and community structures were observed between NG and EG processes. The major contributor to NG process was bacterial communities with 32.04% contribution. While EG process was more dependent on the interactions (73.16% contribution) between the bacterial communities and environmental variables (operational parameters and self-adaptive variable). EG process had higher relative abundances of functional bacteria than NG process. Glycogen accumulating organisms (GAOs) related bacteria with a total relative abundance of maximum 65.43% might be mainly responsible for the faster EG process. This study provided microbial insights for practical application of AGS technology that inoculating crushed AGS might be an effective way to cultivate AGS.

Functional Network-Based Statistics Reveal Abnormal Resting-State Functional Connectivity in Minimal Hepatic Encephalopathy.

Purpose: Whole-brain functional network analysis is an emerging methodology for exploring the mechanisms underlying hepatic encephalopathy (HE). This study aimed to identify the brain subnetwork that is significantly altered within the functional connectome in minimal HE (MHE), the earliest stage of HE. Materials and Methods: The study enrolled 19 cirrhotic patients with MHE and 19 controls who underwent the resting-state functional magnetic resonance imaging and cognitive assessment based on the Psychometric Hepatic Encephalopathy Score (PHES). A whole-brain functional connectivity (FC) matrix was calculated for each subject. Then, network-based statistical analyses of the functional connectome were used to perform group comparisons, and correlation analyses were conducted to identify the relationships between FC alterations and cognitive performance. Results: MHE patients showed significant reduction of positive FC within a subnetwork that predominantly involved the regions of the default-mode network, such as the bilateral posterior cingulate gyrus, bilateral medial prefrontal cortex, bilateral hippocampus and parahippocampal gyrus, bilateral angular gyrus, and left lateral temporal cortex. Meanwhile, MHE patients showed significant reduction of negative FC between default-mode network regions (such as the bilateral posterior cingulate gyrus, medial prefrontal cortex, and angular gyrus) and the regions involved in the somatosensory network (i.e., bilateral precentral and postcentral gyri) and the language network (i.e., the bilateral Rolandic operculum). The correlations of FC within the default-mode subnetwork and PHES results were noted. Conclusion: Default-mode network dysfunction may be one of the core issues in the pathophysiology of MHE. Our findings support the notion that HE is a neurological disease related to intrinsic brain network disruption.

Prevalence of Atrial Fibrillation in Hospital Encounters With End-Stage COPD on Home Oxygen: National Trends in the United States.

BACKGROUND: This study aimed to evaluate the prevalence of atrial fibrillation (AF) in hospital encounters with end-stage COPD on home oxygen admitted for COPD exacerbation. METHODS: We used the 2003 to 2014 Nationwide Inpatient Sample to conduct a retrospective analysis. This study included all patients ≥ 18 years of age with a primary diagnosis of COPD on home oxygen who were hospitalized for COPD exacerbation. We used multivariate-adjusted models to evaluate the association of AF with clinical factors, cost, length of stay, and hospital outcomes. RESULTS: In total, 1,345,270 patients were included; of these, 244,488 (18.2%) had AF. The AF prevalence increased from 12.9% in 2003 to 21.3% in 2014 (P < .0001) and varied by age, sex, race, income, insurance type, and hospital region. Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF. Presence of AF was a risk predictor for in-hospital death (OR, 1.54; 95% CI, 1.45-1.65), acute respiratory failure (OR, 1.09; 95% CI, 1.06-1.12), invasive mechanical ventilation (OR, 1.37; 95% CI, 1.29-1.47), noninvasive mechanical ventilation (OR, 1.14; 95% CI, 1.09-1.18), acute kidney injury (OR, 1.09; 95% CI, 1.04-1.13), sepsis (OR, 1.23; 95% CI, 1.10-1.37), and stroke (OR, 1.80; 95% CI, 1.40-2.32). AF was also associated with increased cost and length of stay. CONCLUSIONS: AF prevalence in hospital encounters with end-stage COPD increased from 2003 to 2014. Better management strategies for patients with end-stage COPD comorbid with AF are needed, especially in elderly individuals.

Altered Topological Properties of Gray Matter Structural Covariance Networks in Minimal Hepatic Encephalopathy.

Background and Aims: Liver cirrhosis commonly induces brain structural impairments that are associated with neurological complications (e.g., minimal hepatic encephalopathy (MHE)), but the topological characteristics of the brain structural network are still less well understood in cirrhotic patients with MHE. This study aimed to conduct the first investigation on the topological alterations of brain structural covariance networks in MHE. Methods: This study included 22 healthy controls (HCs) and 22 cirrhotic patients with MHE. We calculated the gray matter volume of 90 brain regions using an automated anatomical labeling (AAL) template, followed by construction of gray matter structural covariance networks by thresholding interregional structural correlation matrices as well as graph theoretical analysis. Results: MHE patients showed abnormal small-world properties of the brain structural covariance network, i.e., decreased clustering coefficient and characteristic path length and lower small-worldness parameters, which indicated a tendency toward more random architecture. In addition, MHE patients lost hubs in the prefrontal and parietal regions, although they had new hubs in the temporal and occipital regions. Compared to HC, MHE patients had decreased regional degree/betweenness involving several regions, primarily the prefrontal and parietal lobes, motor region, insula and thalamus. In addition, the MHE group also showed increased degree/betweenness in the occipital lobe and hippocampus. Conclusion: These results suggest that MHE leads to altered coordination patterns of gray matter morphology and provide structural evidence supporting the idea that MHE is a neurological complication related to disrupted neural networks.