Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: A meta-analysis

Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients

A Heterozygous Missense hERG Mutation Associated with Early Repolarization Syndrome

Background/Aims: Early repolarization syndrome (ERS) has been recently recognized as early repolarization pattern with idiopathic ventricular fibrillation. However, the genetic background of ERS has not been fully understood. Methods: A Chinese family with sudden cardiac death associated with ERS was investigated. Direct sequencing of ERS susceptibility genes was performed on the proband and family members. Whole-cell patch-clamp methods were used to characterize the mutant channel expressed in HEK 293 cells. Results: One missense mutation (p. K801T) was found in the hERG (KCNH2 gene) by the direct sequencing of candidate genes. Whole cell voltage clamp studies of the K801T mutation in HEK 293 cells demonstrated a 1.5-fold increase in maximum steady state current (37.2±7.3 vs 20.3±4.4 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -59.5±1.4 vs K801T -44.3±1.2 mV). Kinetic analysis revealed slower inactivation rates of K801T, but faster rates of activation and deactivation. The hERG channel blockers tested inhibited K801T-hERG channel in concentration response, and the potencies of these drugs can be rank-ordered as follows: quinidine> disopyramide> sotalol> flecainide. Conclusion: Our study indicated that the K801T mutation caused the gain of function of hERG channels that may account for the clinical phenotype of ERS. Quinidine and disopyramide could improve the function of K801T-hERG mutant channel, and may be therapeutic options for patients with the K801T hERG mutation

Experimental Twin-Field Quantum Key Distribution Over 1000 km Fiber Distance

Quantum key distribution (QKD) aims to generate secure private keys shared by two remote parties. With its security being protected by principles of quantum mechanics, some technology challenges remain towards practical application of QKD. The major one is the distance limit, which is caused by the fact that a quantum signal cannot be amplified while the channel loss is exponential with the distance for photon transmission in optical fiber. Here using the 3-intensity sending-or-not-sending protocol with the actively-odd-parity-pairing method, we demonstrate a fiber-based twin-field QKD over 1002 km. In our experiment, we developed a dual-band phase estimation and ultra-low noise superconducting nanowire single-photon detectors to suppress the system noise to around 0.02 Hz. The secure key rate is $9.53\times10^{-12}$ per pulse through 1002 km fiber in the asymptotic regime, and $8.75\times10^{-12}$ per pulse at 952 km considering the finite size effect. Our work constitutes a critical step towards the future large-scale quantum network.Comment: 47 pages, 17 figure

The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk

AbstractBackgroundLarge cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events.ObjectivesThis study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause.MethodsWe performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.ResultsThirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses.ConclusionsAdministration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality

The role of glucocorticoids in increasing cardiovascular risk

IntroductionDifferent studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke.MethodsWe performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.ResultsA total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15–1.40), CHD (RR = 1.25, 95% CI: 1.11–1.41), and HF (RR = 1.92, 95% CI: 1.51–2.45). The MACE risk increased by 10% (95% CI: 6%–15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%–83%) for an additional 10 μg daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29–17.58) cases per 1,000 person-years.ConclusionsAdministration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs

Tapered microfiber MZI Biosensor for highly sensitive detection of Staphylococcus aureus

A new double-taper microfiber Mach-Zehnder interferometer (MZI) biosensor is applied for Staphylococcus aureus (S. aureus) detection. The microfiber MZI structure is fabricated by creating two tapers along a traditional single mode fiber (SMF) firstly and tapering the SMF sandwiched between two tapers into very small diameter (in the order of micrometers). The measured refractive index (RI) sensitivity of the microfiber MZI is up to 2731.1 nm/RIU in the RI range of 1.34 when the taper waist diameter was 10.2 μm, which is in good agreement with numerical simulation results by using the beam propagation method (BPM). The microfiber MZI functionalized with pig immunoglobulin (pig IgG) could be used to specifically binding to S. aureus. In experiment, the maximum wavelength shift of 1.408 nm was achieved when the microfiber biosensors were immersed into S. aureus with concentration of 7×101 CFU/mL. The limit of detection (LoD) of the microfiber biosensor for S. aureus is calculated as low as 11 CFU/mL. The proposed microfiber MZI biosensor has advantages of simple structure configuration, high sensitivity, good repeatability and specificity, wide detection range and fast detection response time (<30 minutes) and thus was demonstrated a good application prospect in food safety inspection, biochemical sensing, diseases and medical diagnostics

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mechanics and composition of middle cerebral arteries from simulated microgravity rats with and without 1-h/d -Gx gravitation

Background: To elucidate further from the biomechanical aspect whether microgravity-induced cerebral vascular maladaptation might be a contributing factor to postflight orthostatic intolerance and the underlying mechanism accounting for the potential effectiveness of intermittent artificial gravity (IAG) in preventing this adverse effect. Methodology/Principal Findings: Middle cerebral arteries (MCAs) were isolated from 28-day SUS (tail-suspended, headdown tilt rats to simulate microgravity effect), S+D (SUS plus 1-h/d -Gx gravitation by normal standing to simulate IAG), and CON (control) rats. Vascular myogenic reactivity and circumferential stress-strain and axial force-pressure relationships and overall stiffness were examined using pressure arteriography and calculated. Acellular matrix components were quantified by electron microscopy. The results demonstrate that myogenic reactivity is susceptible to previous pressure-induced, serial constrictions. During the first-run of pressure increments, active MCAs from SUS rats can strongly stiffen their wall and maintain the vessels at very low strains, which can be prevented by the simulated IAG countermeasure. The strains are 0.03 and 0.14 respectively for SUS and S+D, while circumferential stress being kept at 0.5 (106 dyn/cm2). During the second-run pressure steps, both the myogenic reactivity and active stiffness of the three groups declined. The distensibility of passive MCAs from S+D is significantly higher than CON and SUS, which may help to attenuate the vasodilatation impairment at low levels of pressure. Collagen and elastin percentages were increased and decreased, respectively, in MCAs from SUS and S+D as compared with CON; however, elastin was higher in S+D than SUS rats. Conclusions: Susceptibility to previous myogenic constrictions seems to be a self-limiting protective mechanism in cerebral small resistance arteries to prevent undue cerebral vasoconstriction during orthostasis at 1-G environment. Alleviating of active stiffening and increasing of distensibility of cerebral resistance arteries may underlie the countermeasure effectiveness of IAG

Associations of Renal Function Trajectories and Long‐Term Cardiovascular Risks Among a Population Without Chronic Kidney Disease

Background The longitudinal trajectories of renal function have been associated with cardiovascular events in patients with chronic kidney disease (CKD). However, the change pattern of renal function in those without CKD has not yet been reported. We aim to explore patterns of renal function change in a non‐CKD population and its associated risks with cardiovascular outcomes. Methods and Results The present study analyzed data from 4 prospective cohorts and was restricted to participants without baseline CKD. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, chronic heart failure, stroke, and cardiovascular deaths. We used a group‐based trajectory model to identify latent groups and analyzed the associated risk with Cox regression models. The complete dates of this study were June 1, 2020, through January 1, 2021. The final sample comprised 23 760 participants (mean age, 58.63 [9.12] years, 10 618 men, and 17 799 White participants). During 20.56 years follow‐up, 8328 (35.05%) first major adverse cardiovascular events happened. Four trajectories in estimated glomerular renal function and 3 patterns of CKD progression were identified. Compared with subjects assigned to class I trajectory (high to mildly decreased group), the adjusted hazard ratios of major adverse cardiovascular events for class II (normal to mildly decreased group), class III (normal to moderately decreased group), and class IV (mildly to severely decreased group) were 1.11 (95% CI, 1.01–1.23), 1.27 (95% CI, 1.14–1.40), and 1.56 (95% CI, 1.38–1.77), respectively. Likewise, participants assigned to the slow and rapid progression groups had elevated HRs for major adverse cardiovascular events (1.75 [95% CI, 1.39–2.21] and 2.19 [95% CI, 1.68–2.86], respectively) when compared with the stable group. Findings were generally consistent in stratification analysis, but significant interaction effects by age and smoking status were detected. Conclusions In this study, we identified unique trajectory groups for renal function. These findings may signal an underlying high‐risk population and inspire future studies on individualized risk management