Dose-response association between transportation noise exposure and type 2 diabetes: A systematic review and meta-analysis of prospective cohort studies.

AIMS: To examine the longitudinal association between transportation noise exposure (road traffic, aircraft, and railway noise) and T2D in a meta-analysis. MATERIALS AND METHODS: We systematically searched PubMed, Embase, Scopus, Cochrane, and Web of Science published up to February 2022. The GRADE approach was used to evaluate the study quality, and the pooled effect estimate was calculated by the fixed-effects model or the random-effects model. RESULTS: We included 10 prospective studies with a total of 4,994,171 participants and 417,332 T2D cases in the meta-analysis. According to the Navigation guide, 8 studies out of 10 were rated as having a probably high or high risk of bias. For road noise, the pooled relative risk (RR) per 10 dB higher Lden for developing T2D was 1.06 (95% CI:1.03, 1.09) with high heterogeneity (I2  = 90.1%, p < 0.001). Similar associations were also observed in aircraft and railway noise: the pooled RR were separately were: 1.01 (1.00, 1.01) and 1.02 (1.01, 1.03) separately. A 'dose-response' analysis found a similar linear association between road noise exposure and the risk of T2D. CONCLUSIONS: An overall 6% increase in the risk of T2D per 10 dB increase in road exposure was observed. Further studies are needed to confirm our findings, especially for aircraft and railway noise, and to identify the mechanisms involved.

Association between serum calcium level and type 2 diabetes: An NHANES analysis and Mendelian randomization study.

AIMS: This study investigated the association between serum calcium levels and the prevalence of T2D using a cross-sectional study and Mendelian randomization analysis. METHODS: Cross-sectional data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Serum calcium levels were divided into three groups (low, medium and high groups) according to the tertiles. Logistic regression was used to estimate the association between serum calcium levels and T2D prevalence. Instrumental variables for serum calcium levels were obtained from the UK Biobank and a two-sample MR analysis was performed to examine the causal relationship between genetically predicted serum calcium levels and the risk of T2D. RESULTS: A total of 39,645 participants were available for cross-sectional analysis. After adjusting for covariates, participants in the high serum calcium group had significantly higher odds of T2D (OR = 1.18, 95% CI = 1.07, 1.30, p = 0.001) than those in the moderate group. Restricted cubic spline plots showed a J-shaped curve relationship between serum calcium level and prevalence of T2D. Consistently, Mendelian randomization analysis showed that higher genetically predicted serum calcium levels were causally associated with a higher risk of T2D (OR = 1.16, 95% CI: 1.01, 1.33, p = 0.031). CONCLUSIONS: The results of this study suggest that higher serum calcium levels are causally associated with a higher risk of T2D. Further studies are needed to clarify whether intervening in high serum calcium could reduce the risk of T2D.

Living alone and the risk of depressive symptoms: a cross-sectional and cohort analysis based on the China Health and Retirement Longitudinal Study.

BACKGROUND: There were a few studies that examined the longitudinal association between living alone and depressive symptoms, and the vast majority of them were conducted in patients with certain diseases, such as heart failure, cancer, and glaucoma. This study aimed to examine the association between living alone and depressive symptoms in a large representative older Chinese population. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) data from 2015 to 2018 were used. Living alone was defined as participants who did not live with others ever or more than 11 months in the past year at baseline. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies-Depression Scale (CES-D10). The multivariate logistic regression was used to estimate the relationship between living alone and depressive symptoms. RESULTS: There were 5,311 and 2,696 participants ≥ 60 years old included in the cross-sectional and cohort analysis, respectively. The risk of depressive symptoms in participants who lived alone was significantly higher than those who lived with others in both cross-sectional (OR:1.33; 95%CI:1.14,1.54) and cohort analysis (OR:1.23; 95%CI:0.97,1.55). There was a significant interaction between financial support and living alone (Pinteraction = 0.008) on the risk of depressive symptoms. Stratified analyses showed that, compared to those who lived with others, the risk of depressive symptoms in participants who lived alone increased by 83% (OR:1.83; 95%CI:1.26,2.65) in participants receiving lower financial support. However, we did not find statistically significant associations in participants with medium (OR:1.10; 95%CI: 0.74,1.63) and higher financial support (OR: 0.87; 95%CI: 0.53,1.41). CONCLUSION: Living alone was associated with a higher risk of depressive symptoms in the Chinese older population, and this association was moderated by the receipt of financial support. Living alone may be an effective and easy predictor for early identification of high-risk populations of depression in the older population.

Anti-scarring effects of conbercept on human Tenon's fibroblasts: comparisons with bevacizumab.

BACKGROUND: Safely inhibiting the formation of scar in the glaucoma filtration surgery (GFS) has always been an issue for clinical glaucoma doctors. Anti-vascular endothelial growth factor (VEGF) agents can reduce angiogenesis, and anti-placental growth factor (PIGF) agents can affect reactive gliosis. However, the effect of conbercept, which can bind to both VEGF and PIGF, on human Tenon's fibroblasts (HTFs) is unknown. METHODS: HTFs were cultured in vitro and treated with conbercept or bevacizumab (BVZ). No drug was added to the control group. The effects of drugs on cell proliferation were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the collagen type I alpha1(Col1A1) mRNA expression level was measured using quantitative polymerase chain reaction (qPCR). HTF cell migration after drug interventions was evaluated using the scratch wound assay along with the measurement of the expression levels of VEGF and PIGF in human umbilical vein endothelial cells (HUVECs) using enzyme-linked immunosorbent assay, as well as the detection of the VEGF(R) mRNA expression level in HTFs using qPCR. RESULTS: After the addition of conbercept (0.01, 0.1, and 1 mg/mL) to the cultured HTFs or HUVECs, no significant cytotoxicity was observed compared with the control group, while the cytotoxicity of 2.5 mg/mL BVZ on HTFs was obvious. Conbercept significantly inhibited HTF cell migration and Col1A1 mRNA expression level in HTFs. It was superior to BVZ in inhibiting HTF migration. After the intervention with conbercept, the expression level of PIGF and VEGF in HUVECs significantly decreased; and the inhibitory effect of conbercept on the expression level of VEGF in HUVECs was weaker than that of BVZ. Conbercept was more advantageous than BVZ in inhibiting the expression level of VEGFR-1 mRNA in HTFs. However, its effect in terms of inhibiting the expression level of VEGFR-2 mRNA in HTFs was weaker than that of BVZ. CONCLUSION: The results suggested the low cytotoxicity and significant anti-scarring effect of conbercept in HTF with significant anti-PIGF and inferior anti-VEGF effects compared with BVZ, thus providing a better understanding of the role of conbercept in the GFS wound healing process.

Environmental noise exposure and health outcomes: an umbrella review of systematic reviews and meta-analysis.

BACKGROUND: Environmental noise is becoming increasingly recognized as an urgent public health problem, but the quality of current studies needs to be assessed. To evaluate the significance, validity and potential biases of the associations between environmental noise exposure and health outcomes. METHODS: We conducted an umbrella review of the evidence across meta-analyses of environmental noise exposure and any health outcomes. A systematic search was done until November 2021. PubMed, Cochrane, Scopus, Web of Science, Embase and references of eligible studies were searched. Quality was assessed by AMSTAR and Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Of the 31 unique health outcomes identified in 23 systematic reviews and meta-analyses, environmental noise exposure was more likely to result in a series of adverse outcomes. Five percent were moderate in methodology quality, the rest were low to very low and the majority of GRADE evidence was graded as low or even lower. The group with occupational noise exposure had the largest risk increment of speech frequency [relative risk (RR): 6.68; 95% confidence interval (CI): 3.41-13.07] and high-frequency (RR: 4.46; 95% CI: 2.80-7.11) noise-induced hearing loss. High noise exposure from different sources was associated with an increased risk of cardiovascular disease (34%) and its mortality (12%), elevated blood pressure (58-72%), diabetes (23%) and adverse reproductive outcomes (22-43%). In addition, the dose-response relationship revealed that the risk of diabetes, ischemic heart disease (IHD), cardiovascular (CV) mortality, stroke, anxiety and depression increases with increasing noise exposure. CONCLUSIONS: Adverse associations were found for CV disease and mortality, diabetes, hearing impairment, neurological disorders and adverse reproductive outcomes with environmental noise exposure in humans, especially occupational noise. The studies mostly showed low quality and more high-quality longitudinal study designs are needed for further validation in the future.

A Review of Piezoelectric Footwear Energy Harvesters: Principles, Methods, and Applications.

Over the last couple of decades, numerous piezoelectric footwear energy harvesters (PFEHs) have been reported in the literature. This paper reviews the principles, methods, and applications of PFEH technologies. First, the popular piezoelectric materials used and their properties for PEEHs are summarized. Then, the force interaction with the ground and dynamic energy distribution on the footprint as well as accelerations are analyzed and summarized to provide the baseline, constraints, potential, and limitations for PFEH design. Furthermore, the energy flow from human walking to the usable energy by the PFEHs and the methods to improve the energy conversion efficiency are presented. The energy flow is divided into four processing steps: (i) how to capture mechanical energy into a deformed footwear, (ii) how to transfer the elastic energy from a deformed shoes into piezoelectric material, (iii) how to convert elastic deformation energy of piezoelectric materials to electrical energy in the piezoelectric structure, and (iv) how to deliver the generated electric energy in piezoelectric structure to external resistive loads or electrical circuits. Moreover, the major PFEH structures and working mechanisms on how the PFEHs capture mechanical energy and convert to electrical energy from human walking are summarized. Those piezoelectric structures for capturing mechanical energy from human walking are also reviewed and classified into four categories: flat plate, curved, cantilever, and flextensional structures. The fundamentals of piezoelectric energy harvesters, the configurations and mechanisms of the PFEHs, as well as the generated power, etc., are discussed and compared. The advantages and disadvantages of typical PFEHs are addressed. The power outputs of PFEHs vary in ranging from nanowatts to tens of milliwatts. Finally, applications and future perspectives are summarized and discussed.

Associations of PM2.5 and road traffic noise with mental health: Evidence from UK Biobank.

BACKGROUND: The associations of atmospheric particulate matter with diameters of 2.5 µm or less (PM2.5) and road traffic noise with mental disorders in men and women are not well studied. OBJECTIVES: We aim to examine the cross-sectional associations of PM2.5 and road traffic noise with mental disorders in men and women. METHODS: The baseline data of the UK Biobank study (2006-2010) were used. Mental disorders including symptoms of nerves, anxiety, tension or depression (NATD), major depression, and bipolar disorder were assessed by validated questions. Verified models were used to estimate PM2.5 and road traffic noise. RESULTS: A total of 334,986 participants with measurements of NATD and 90,706 participants with measurements of major depression and bipolar disorder were included in the analysis. After adjusting for covariates, the odds for the risk of NATD symptoms increased by 2.31 (95% CI: 2.15-2.50) times per 10 µg/m3 increase in PM2.5. The odds for the risk of major depression and bipolar disorder increased by 2.26 and 4.99 times per 10 µg/m3 increase in PM2.5. On the other hand, higher road traffic noise exposure was significantly associated with a higher risk of NATD symptoms (Decile 6-8 (54.9-57.8 dB), OR: 1.03, 95% CI: 1.01-1.06; Decile 9-10 (≥57.8 dB), OR: 1.04, 95% CI: 1.01-1.07) and bipolar disorder (Decile 2-5 (52.1-54.9 dB), OR: 1.26, 95% CI: 1.00-1.59; Decile 6-8 (54.9-57.8 dB), OR: 1.30, 95% CI: 1.02-1.65; Decile 9-10 (≥57.8 dB), OR: 1.54, 95% CI: 1.21-1.97). Interestingly, a negative association was observed between moderate road traffic noise and major depression (Decile 2-5 (52.1-54.9 dB), OR: 0.95, 95% CI: 0.90-1.00). Interactions between PM2.5 exposure with age, gender, and sleeplessness for NATD symptoms were observed (P < 0.05), while interactions between road traffic noise exposure with age and gender were observed (P < 0.05). CONCLUSIONS: We found a positive association between PM2.5 and mental disorders. Meanwhile, we found a positive association of road traffic noise with NATD symptoms and bipolar disorder and a negative association of moderate road traffic noise with major depression. Also, the effect modifications of these associations by age, gender, or sleeplessness may exist.

Associations of road traffic noise with cardiovascular diseases and mortality: Longitudinal results from UK Biobank and meta-analysis.

BACKGROUND: Epidemiological evidence suggests potential associations of road traffic noise exposure with cardiovascular disease (CVD) and mortality, but uncertainty remains. OBJECTIVES: We examined the association of road traffic noise with the risk of CVD and mortality in a large longitudinal cohort study and meta-analysis. METHODS: We analyzed 342, 566 participants from the UK Biobank who were free of CVD at baseline and had complete covariate data. We also performed a meta-analysis of road traffic noise effects on CVD and mortality by including qualified cohort studies published before April 2021. RESULTS: After adjustment for potential confounders, the odds for the risk of stroke, CVD, and all-cause mortality increased by 1.07 (95%CI: 1.01-1.13, P = 0.019), 1.13 (95%CI: 1.04-1.22, P = 0.003) and 1.08 (95%CI: 1.04-1.12, P < 0.001) times per 10 dB increases in road traffic noise, respectively. Among men, high road traffic noise exposure was significantly associated with an increased risk in stroke (HR = 1.08 per 10 dB increase, 95%CI: 1.00-1.16, P = 0.043), CVD (HR = 1.12 per 10 dB increase, 95%CI: 1.02-1.23, P = 0.020) and all-cause mortality (HR = 1.12 per 10 dB increase, 95%CI: 1.07-1.17 P < 0.001), whereas we did not find a significant association in women. The meta-analysis showed that road traffic noise exposure was significantly associated with a high risk of stroke (risk ratio [RR]: 1.06, 95% CI: 1.02-1.11), CVD mortality (RR: 1.03, 95% CI: 1.00-1.05), all-cause mortality (RR: 1.05, 95% CI: 1.02-1.07). CONCLUSIONS: This study provides more evidence of increased risk of stroke, CVD, and all-cause mortality in association with exposure to road traffic noise pollution, especially in men.

[Analysis of phenotype and MYH7 gene variant in a family of patients with hypertrophic cardiomyopathy].

OBJECTIVE: To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM). METHODS: The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software. RESULTS: 6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5). CONCLUSION: The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.

Extracellular Vesicle-Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models.

BACKGROUND: Stroke is a leading cause of adult disability that can severely compromise the quality of life of patients, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA (circRNA) molecules are known to function in ischemic brain injury. Lentivirus-based expression systems have been widely used in basic studies of circRNAs, but safety issues with such delivery systems have limited exploration of the potential therapeutic roles for circRNAs. METHODS: Circular RNA SCMH1 (circSCMH1) was screened from the plasma of patients with acute ischemic stroke by using circRNA microarrays. Engineered rabies virus glycoprotein-circSCMH1-extracellular vesicles were generated to selectively deliver circSCMH1 to the brain. Nissl staining was used to examine infarct size. Behavioral tasks were performed to evaluate motor functions in both rodent and nonhuman primate ischemic stroke models. Golgi staining and immunostaining were used to examine neuroplasticity and glial activation. Proteomic assays and RNA-sequencing data combined with transcriptional profiling were used to identify downstream targets of circSCMH1. RESULTS: CircSCMH1 levels were significantly decreased in the plasma of patients with acute ischemic stroke, offering significant power in predicting stroke outcomes. The decreased levels of circSCMH1 were further confirmed in the plasma and peri-infarct cortex of photothrombotic stroke mice. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that circSCMH1 treatment improved functional recovery after stroke in both mice and monkeys, and we discovered that circSCMH1 enhanced the neuronal plasticity and inhibited glial activation and peripheral immune cell infiltration. CircSCMH1 binds mechanistically to the transcription factor MeCP2 (methyl-CpG binding protein 2), thereby releasing repression of MeCP2 target gene transcription. CONCLUSIONS: Rabies virus glycoprotein-circSCMH1-extracellular vesicles afford protection by promoting functional recovery in the rodent and the nonhuman primate ischemic stroke models. Our study presents a potentially widely applicable nucleotide drug delivery technology and demonstrates the basic mechanism of how circRNAs can be therapeutically exploited to improve poststroke outcomes.

Down-regulation of circular RNA CDC14A peripherally ameliorates brain injury in acute phase of ischemic stroke.

BACKGROUND: Inflammation is integral to the pathophysiology of ischemic stroke and a prime target for the development of new stroke therapies. The aim of the present study is to seek out the regulatory mechanism of circCDC14A in neuroinflammatory injury in tMCAO mice. METHODS: The expression level of circCDC14A in peri-infarct cortex and plasma of mice were detected by qPCR. The localization of circCDC14A in peripheral blood cells and peri-infarct cortex of tMCAO mice were explored by in situ hybridization and immunofluorescence colocalization staining. Lentivirus were microinjected into lateral ventricular of brain or injected into tail vein to interfere with the expression of circCDC14A, thus their effects on behavior, morphology, and molecular biology of tMCAO mice were analyzed. RESULTS: The expression of circCDC14A in plasma and peri-infarct cortex of tMCAO mice significantly increased, and circCDC14A was mainly localized in neutrophils peripherally while in astrocytes in peri-infarct cortex centrally. Tail vein injection of lentivirus to interfere with the expression of circCDC14A significantly reduced the infarct volume (P < 0.01) at 72 h after reperfusion and density of activated astrocytes in peri-infarct cortex at 3 days, 5 days and 7 days after tMCAO modeling (all P < 0.0001). Moreover, mNSS (P < 0.0001) and survival rate (P < 0.001) were significantly improved within 7 days in si-circCDC14A group compared to circCon group. Additionally, morphology analysis showed the volume and surface area of each activated astrocytes significantly decreased (P < 0.0001). Quantification analysis measured the percentage of N2 phenotype among infiltrated neutrophils in brain sections and found N2 ratio was significantly higher in si-circCDC14A group compared to circCon group (P < 0.001). CONCLUSION: Knocking down the expression of circCDC14A in peripheral blood cells relieved astrocytes activation in peri-infarct cortex, thereby relieved brain damage in the acute phase of ischemic stroke.

Florfenicol Enhances Colonization of a Salmonella enterica Serovar Enteritidis floR Mutant with Major Alterations to the Intestinal Microbiota and Metabolome in Neonatal Chickens.

Florfenicol is an important antibiotic commonly used in poultry production to prevent and treat Salmonella infection. However, oral administration of florfenicol may alter the animals' natural microbiota and metabolome, thereby reducing intestinal colonization resistance and increasing susceptibility to Salmonella infection. In this study, we determined the effect of florfenicol (30 mg/kg of body weight) on gut colonization of neonatal chickens challenged with Salmonella enterica subsp. enterica serovar Enteritidis. We then analyzed the microbial community structure and metabolic profiles of cecal contents using microbial 16S amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics, respectively. We also screened the marker metabolites using a multi-omics technique and assessed the effect of these markers on intestinal colonization by S. Enteritidis. Florfenicol administration significantly increased the loads of S. Enteritidis in cecal contents, spleen, and liver and prolonged the residence of S. Enteritidis. Moreover, florfenicol significantly affected cecal colony structures, with reduced abundances of Lactobacillus and Bacteroidetes and increased levels of Clostridia, Clostridium, and Dorea. The metabolome was greatly influenced by florfenicol administration, and perturbation in metabolic pathways related to linoleic acid metabolism (linoleic acid, conjugated linoleic acid [CLA], 12,13-EpOME, and 12,13-diHOME) was most prominently detected. We screened CLA and 12,13-diHOME as marker metabolites, which were highly associated with Lactobacillus, Clostridium, and Dorea. Supplementation with CLA maintained intestinal integrity, reduced intestinal inflammation, and accelerated Salmonella clearance from the gut and remission of enteropathy, whereas treatment with 12,13-diHOME promoted intestinal inflammation and disrupted intestinal barrier function to sustain Salmonella infection. Thus, these results highlight that florfenicol alters the intestinal microbiota and metabolism of neonatal chickens and promotes Salmonella infection mainly by affecting linoleic acid metabolism. IMPORTANCE Florfenicol is a broad-spectrum fluorine derivative of chloramphenicol frequently used in poultry to prevent/treat Salmonella. However, oral administration of florfenicol may lead to alterations in the microbiota and metabolome in the chicken intestine, thereby reducing colonization resistance to Salmonella infection, and the possible mechanisms linking antibiotics and Salmonella colonization in poultry have not yet been fully elucidated. In the current study, we show that increased colonization by S. Enteritidis in chickens administered florfenicol is associated with large shifts in the gut microbiota and metabolic profiles. The most influential linoleic acid metabolism is highly associated with the abundances of Lactobacillus, Clostridium, and Dorea in the intestine. The screened target metabolites in linoleic acid metabolism affect S. Enteritidis colonization, intestinal inflammation, and intestinal barrier function. Our findings provide a better understanding of the susceptibility of animal species to Salmonella after antibiotic intervention, which may help to elucidate infection mechanisms that are important for both animal and human health.

Trans-Septal Myocardial Biopsy in Hypertrophic Cardiomyopathy Using the Liwen Procedure: An Introduction of a Novel Technique.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety of myocardial biopsy using a new approach, the Liwen procedure. BACKGROUND: Myocardial biopsy is essential when other methods could not differentiate other etiologies from hypertrophic obstructive cardiomyopathy (HOCM). Our previous work using intramyocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy (Liwen procedure) may provide another approach to obtain the myocardial samples. METHOD: Seventeen patients with HOCM were enrolled for biopsies through percutaneously accessed intramyocardial septum and evaluated possible complications. RESULTS: We obtained 31 specimens from 17 patients with a success rate of sample acquisition 100.0%. The number of myocardial samples taken per patient was 1.8 ± 0.8, and the average length of all samples was 16.7 ± 5.6 mm which could be used for pathological diagnosis. The complications included pericardial effusion with and without tamponade in one patient (5.9%), and no incidence of nonsustained and sustained ventricular tachycardia, conduction abnormity, perforation, stroke, and pneumothorax. The inhospital and 30-day mortality was 0%. CONCLUSION: This study has shown that myocardial biopsy of the Liwen procedure is relatively safe and technically feasible with adequate tissue sampling, which may help pathological diagnosis and further research of HOCM of diverse etiologies. This trial is registered with NCT04355260.

Predictors of cardiac involvement and survival in patients with primary systemic light-chain amyloidosis: roles of the clinical, chemical, and 3-D speckle tracking echocardiography parameters.

BACKGROUND: Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis with poor prognosis. Currently, the predictors of cardiac involvement and prognostic staging systems are primarily based on conventional echocardiography and serological biomarkers. We used three-dimensional speckle tracking echocardiography (STE-3D) measurements of strain, hypothesizing that it could detect cardiac involvement and aid in prediction of mortality. METHODS: We retrospectively analysed 74 consecutive patients with biopsy-proven AL amyloidosis. Among them, 42 showed possible cardiac involvement and 32 without cardiac involvement. LV global longitudinal strain (GLS), global radial strain, global circumferential strain and global area strain (GAS) measurements were obtained. RESULTS: The GLS and GAS were considered significant predictors of cardiac involvement. The cut-off values discriminating cardiac involvement were 16.10% for GLS, 32.95% for GAS. During the median follow-up of 12.5 months (interquartile range 4-25 months), 20 (27%) patients died. For the Cox proportional model survival analysis, heart rate, cardiac troponin T, NT-proBNP levels, E/e', GLS, and GAS were univariate predictors of death. Multivariate Cox model showed that GLS ≤ 14.78% and cardiac troponin T ≥ 0.049 mg/l levels were independent predictors of survival. CONCLUSIONS: STE-3D measurements of LV myocardial mechanics could detect cardiac involvement in patients with AL amyloidosis; GLS and cardiac biomarkers can provided prognostic information for mortality prediction.

Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K.

The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.

Circulating Circular RNAs as Biomarkers for the Diagnosis and Prediction of Outcomes in Acute Ischemic Stroke.

Background and Purpose- Circular RNAs (CircRNAs) show promise as stroke biomarkers because of their participation in various pathophysiological processes associated with acute ischemic stroke (AIS) and stability in peripheral blood. Methods- A circRNA microarray was used to identify differentially expressed circulating circRNAs in a discovery cohort (3 versus 3). Validation (36 versus 36) and replication (200 versus 100) were performed in independent cohorts by quantitative polymerase chain reaction. Platelets, lymphocytes, and granulocytes were separated from blood to examine the origins of circRNAs. Results- There were 3 upregulated circRNAs in Chinese population-based AIS patients compared with healthy controls. The combination of 3 circRNAs resulted in an area under the curve of 0.875, corresponding to a specificity of 91% and a sensitivity of 71.5% in AIS diagnosis. Furthermore, the combination of change rate in 3 circRNAs within the first 7 days of treatment showed an area under the curve of 0.960 in predicting stroke outcome. There was significant increase in lymphocytes and granulocytes for circPDS5B (circular RNA PDS5B) and only in granulocytes for circCDC14A (circular RNA CDC14A) in AIS patients compared with healthy controls. Conclusions- Three circRNAs could serve as biomarkers for AIS diagnosis and prediction of stroke outcomes. The elevated levels of circPDS5B and circCDC14A after stroke might be because of increased levels in lymphocytes and granulocytes.

Quantitative Analysis of Left Ventricular Flow Dynamics in Latent Obstructive Hypertrophic Cardiomyopathy Using Vector Flow Mapping.

OBJECTIVES: This study aimed to assess left ventricular (LV) energy loss (EL), circulation and vortex area using vector flow mapping (VFM) in patients with latent obstructive hyper-trophic cardiomyopathy (LOHCM) and nonobstructive hypertrophic cardiomyopathy (NOHCM). METHODS: Fourteen LOHCM patients, 10 NOHCM patients, and 11 healthy individuals were evaluated by transthoracic echocardiography. An offline VFM workstation was used to analyze the LV blood flow patterns and fluid dynamics. The hemodynamic parameters, EL, circulation, and vortex area in 7 cardiac phases were calculated and analyzed. RESULTS: Compared with controls and NOHCM patients, EL was significantly higher in -LOHCM patients during the rapid ejection phase, slow ejection (SE) phase, and isovolumetric relaxation phase (p < 0.05). LOHCM patients also showed increased circulation during SE compared to the other two groups (p < 0.05). The ability to discriminate between NOHCM and LOHCM was assessed by the area under the receiver-operating characteristic curve (AUC), and EL during SE was found to have the largest AUC (0.964); the best cutoff value was 6.34 J/m3/s, with a sensitivity of 100% and specificity of 80%. CONCLUSIONS: The VFM technique can detect abnormal changes of LV EL and vortex characteristics in hypertrophic cardiomyopathy patients. Compared with controls and NOHCM patients, the LOHCM patients have worse systolic and diastolic functions.

Electrocardiographic QRS voltage amplitude improvement by intramyocardial radiofrequency ablation in patients with hypertrophic obstructive cardiomyopathy and one year follow up.

OBJECTIVES: This study aimed to determine whether the serial changes of the electrocardiogram is associated with regression of left ventricular hypertrophy (LVH) after Liwen procedure. BACKGROUND: Clinical application of the echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is an innovative approach to treat hypertrophic obstructive cardiomyopathy (HOCM). METHODS: We enrolled 30 consecutive patients with HOCM who had undergone Liwen procedure in our Hypertrophic Cardiomyopathy Center, from June 2016 to January 2018. Electrocardiography (ECG) and echocardiogram were performed before and after Liwen procedure, and at each follow-up (1-week, 1, 3, 6 months and 1 year). The Sokolow-Lyon index (SLi), Q wave, R wave, S wave amplitude of 12-lead ECG and interventricular septal (IVS) thickness, left ventricular mass index (LVMI) by echocardiograms were measured in each patient. The sum of the ECG QRS amplitude on each lead was calculated. The reduction of SLi and QRS amplitude were used as improvement index. RESULTS: The ECG leads with most improvement rate of the QRS wave amplitude of all cases were V1 and V2, both at 90%. The QRS wave amplitude in V1 leads and SLi were positively correlated with IVS thickness and LVMI at baseline and 1 year after Liwen procedure, respectively. The reduction of IVS thickness, LVMI and QRS wave amplitude in leads V1 and V2 were significant at one month after ablation and the follow-up period. SLi was significantly decreased at 3 months during the observation period. Similarly, the improvement of ECG QRS wave amplitude after the Liwen procedure tracked the gradual thinning of the IVS and the changes of SLi reflected the regression of LVH. CONCLUSION: The QRS wave amplitude reductions in lead V1 and SLi may be good indicators for evaluating the postoperative interventricular septal remodeling of the Liwen procedure.

A novel cfr-carrying Tn7 transposon derivative characterized in Morganella morganii of swine origin in China.

OBJECTIVES: To characterize the presence and genetic environment of the multiresistance gene cfr in bacterial isolates from a swine farm. METHODS: A total of 97 bacterial isolates, recovered from 32 faecal swabs obtained on one farm, were tested for the presence of the cfr gene by PCR. Species identification of the one cfr-positive strain was conducted using the BD PhoenixTM 100 Automated Microbiology System. Susceptibility testing was carried out by broth microdilution. The genetic environment of the cfr gene was analysed by WGS. RESULTS: The Morganella morganii isolate BCMM24 was the only cfr-positive strain. The cfr gene, as well as 15 other resistance genes, is located on a novel 111238 bp transposon derived from Tn7, designated as Tn6451, which comprises various genetic materials including a novel class 1 integron with five gene cassettes. The cfr-containing region consists of a novel genetic structure IS26-cfr-ΔTn554 tnpB-ΔTn3 family tnpA-IS26, differing from previous reports. Two-step PCR results show that the structure can be looped out and that Tn6451 cannot be excised from the chromosome. CONCLUSIONS: To the best of our knowledge, we report the cfr gene in M. morganii for the first time. The cfr gene and 15 other resistance genes are located on a novel Tn7 transposon derivative, suggesting that the Tn7 transposon may act as a reservoir for various antimicrobial resistance genes and more Tn7 derivatives carrying multiple resistance genes are likely to be discovered in Gram-negative bacteria of both animal and human origin.

Prevalence of subcutaneous implantable cardioverter-defibrillator based on template ECG screening and ineligible surface ECG predicting factors in patients with hypertrophic cardiomyopathy in China.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) may provide comparable protection while avoiding the disadvantage of transvenous lead, but the abnormal features of the hypertrophic cardiomyopathy (HCM) electrocardiogram (ECG) make it a challenge for S-ICD template screening. We aimed to investigate S-ICD eligibility according to the S-ICD manufacturer's surface ECG screening template in China, and further analyze its corresponding ineligible predicting factors in 12-lead suface ECG. A total of 179 HCM patients (114 males; mean age: 45 ± 14 years) underwent S-ICD screening at rest and on exercise, among which 91 patients (50.8%) were eligible for S-ICD. Among the patients who passed screening, 43 (47.3%) had 3 vectors eligibility; 64 (70.3%) screening qualified on both sides; 10 patients (11.0%) passed the screening while the electrodes located only on the left parasternal line versus 17 patients (18.7%) moved to the right line. The secondary sensing vector (Lead III) was mostly appropriate (53.6%), followed by the primary sensing vector (lead II, 53.1%) and the alternate sensing vector (Lead I, 46.9%). Higher R wave was the major cause, accounted for 70.5%, for screening failure. There existed significant difference in T wave in lead II, aVF, V5 and V6, adds R/T ratio in lead V5 and V6, between the screening success group (group A) and screening failure group (group B) at rest and on exercise. A multivariable logistic regression analysis was performed to identify that R/T ≤ 3.5 in lead V5 was the independent factor to predict the screening ineligibility, with odds ratio 3.648. S-ICD screening success is 50.8% in HCM patients, which is much lower than that in other studies. R/T ≤ 3.5 in lead V5 in 12-lead surface ECG was an independent predicting factor for screening failure.