The neuronal implementation of representational geometry in primate prefrontal cortex.

Modern neuroscience has seen the rise of a population-doctrine that represents cognitive variables using geometrical structures in activity space. Representational geometry does not, however, account for how individual neurons implement these representations. Leveraging the principle of sparse coding, we present a framework to dissect representational geometry into biologically interpretable components that retain links to single neurons. Applied to extracellular recordings from the primate prefrontal cortex in a working memory task with interference, the identified components revealed disentangled and sequential memory representations including the recovery of memory content after distraction, signals hidden to conventional analyses. Each component was contributed by small subpopulations of neurons with distinct spiking properties and response dynamics. Modeling showed that such sparse implementations are supported by recurrently connected circuits as in prefrontal cortex. The perspective of neuronal implementation links representational geometries to their cellular constituents, providing mechanistic insights into how neural systems encode and process information.

The role of glucocorticoids in increasing cardiovascular risk.

Introduction: Different 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. Methods: We 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. Results: A 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. Conclusions: Administration 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.

Human acute microelectrode array recordings with broad cortical access, single-unit resolution, and parallel behavioral monitoring.

There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level. Recording from the parietal association cortex, a region rarely explored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe traveling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition, including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.

Interleukin-1 blockade treatment decreasing cardiovascular risk.

BACKGROUND: Interleukin-1 (IL-1) played a role in the occurrence and development of atherosclerosis and cardiovascular events. However, the association between IL-1 blockage treatment and reducing of cardiovascular risk remains poorly defined. HYPOTHESIS: IL-1 blockage treatment reduce the risk and incidence rate of overall major adverse cardiovascular events (MACE), all-cause death, acute myocardial infarction(MI), unstable angina and heart failure. METHODS: We performed a search of published reports by using MEDLINE database (January 1, 2005 to April 1, 2018). The randomized controlled trials (RCTs) that reported sample size and occurrence numbers in test group and placebo group for the associations of interest were included. RESULTS: Eight RCT studies involving 15 647 participants were identified. Compared with those who took no IL-1 blockage, patients taking IL-1 blockage experienced a decreased risk of overall MACE (RR 0.88, 95% CI 0.82-0.94), unstable angina (RR 0.80, 95% CI 0.66-0.98), and breakthrough or recurrence of heart failure (RR 0.44, 95% CI 0.22-0.87). No association was found between IL-1 blockage treatment and death from all cause (RR 0.91, 95% CI 0.83-1.00) as well as acute MI (RR 0.85, 95% CI 0.71-1.01). The RRs associated with overall MACE, death from all cause, acute MI, and unstable angina for anakinra were 1.05, 1.16, 2.97, and 0.56, respectively, and for canakinumab were 1.05, 0.91, 0.80, and 0.80, respectively. CONCLUSIONS: Administration of IL-1 blockage was associated with decrease risks of overall MACE, unstable angina, and breakthrough or recurrence of heart failure, but not with death from all cause as well as acute MI.

Long-Term Cardiovascular Risk After Radiotherapy in Women With Breast Cancer.

BACKGROUND: Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We performed a meta-analysis to investigate the link between radiotherapy and long-term cardiovascular morbidity and mortality in patients with breast cancer. METHODS AND RESULTS: We performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95%CIs for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-nine studies involving 1 191 371 participants were identified. Patients who received left-sided radiotherapy, as compared with those receiving right-sided radiotherapy, experienced increased risks of developing coronary heart disease (RR 1.29, 95%CI 1.13-1.48), cardiac death (RR 1.22, 95%CI 1.08-1.37) and death from any cause (RR 1.05, 95%CI 1.01-1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RRs were 1.30 (95%CI 1.13-1.49) for coronary heart disease and 1.38 (95%CI 1.18-1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95%CI 36.8-130.5) cases of coronary heart disease and 125.5 (95%CI 98.8-157.9) cases of cardiac death per 100 000 person-years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality. CONCLUSIONS: Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.

Early repolarization is associated with a significantly increased risk of ventricular arrhythmias and sudden cardiac death in patients with structural heart diseases.

BACKGROUND: Early repolarization pattern (ERP) has been proved to increase risk of arrhythmia death in the general population, but its prognostic significance in patients with structural heart disease (SHD) is controversial. OBJECTIVE: The purpose of this study was to conduct a meta-analysis of studies assessing the association between ERP and risk of ventricular arrhythmias (VTAs) and sudden cardiac death (SCD) in patients with SHD. METHODS: We performed a literature search using MEDLINE (January 1, 1966, to September 25, 2016) and EMBASE (January 1, 1980, to September 25, 2016) with no restrictions. Studies that reported odds ratio (OR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. RESULTS: The search yielded 19 observational studies, involving 7268 patients that reported 1127 cases of VTAs or SCD. In the selected studies, the point estimates of the ORs were consistently greater than 1. Compared with those without ERP, patients with ERP experienced a significantly increased risk of developing VTAs or SCD (OR 4.76; 95% CI 3.62-6.26), ventricular fibrillation (OR 7.14; 95% CI 4.31-11.82), and SCD (OR 4.07; 95% CI 1.58-10.51). The results were consistent and statistically significant in all subgroups. ERP with J-point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk. CONCLUSION: ERP is associated with a significant increased risk of VTAs or SCD in patients with SHD. Future research should attempt to understand the exact mechanisms for the arrhythmia risk and to introduce ERP in the risk stratification in this patient group.

Role of Early Repolarization Pattern in Increasing Risk of Death.

BACKGROUND: An early repolarization pattern (ERP) has been hypothesized to be arrhythmogenic in experimental studies, but the prognostic significance of the ERP in the general population is controversial. We performed a meta-analysis to examine the link between ERP and the risk of sudden cardiac arrest (SCA), cardiac death, and death from any cause. METHODS AND RESULTS: We performed a literature search using MEDLINE (January 1, 1966 to July 31, 2015) and EMBASE (January 1, 1980 to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Sixteen studies involving 334 524 subjects were identified. Compared with those without ERP, subjects with ERP experienced significantly increased risk for developing SCA (RR 2.18; 95% CI 1.29-3.68), cardiac death (RR 1.48; 95% CI 1.06-2.07), and death from any cause (RR 1.21; 95% CI 1.02-1.42), respectively. The increased risk was present predominantly in Asians and whites but not in African Americans. ERP with J-point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk. ERP was associated with an absolute risk increase of 139.6 (95% CI 130.3-149.3) additional SCAs per 100 000 person-years and responsible for 7.3% (95% CI 1.9-15.2) of SCA in the general population. CONCLUSIONS: ERP is associated with significant increased risk for SCA, cardiac death, and death from any cause. Future studies should focus on understanding the exact mechanisms for the arrhythmia risk and developing reliable tools for risk stratification.

The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk.

BACKGROUND: Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. OBJECTIVES: This 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. METHODS: We 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. RESULTS: Thirty-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. CONCLUSIONS: Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.

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.

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.

More favorable response to cardiac resynchronization therapy in women than in men.

BACKGROUND: Data on sex difference in response to cardiac resynchronization therapy (CRT) remain controversial. We conducted a meta-analysis to summarize all published studies to determine whether sex-based differences in response to CRT exist. METHODS AND RESULTS: We performed a literature search using MEDLINE (source PubMed; January 1966 to March 2014) and EMBASE (January 1980 to March 2014) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Seventy-two studies involving 33 434 patients were identified. Overall, female patients had better outcomes from CRT compared with male patients, with a significant 33% reduction in the risk of death from any cause (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74; P<0.001), 20% reduction in death or hospitalization for heart failure (hazard ratio, 0.80; 95% confidence interval, 0.71-0.90; P<0.001), 41% reduction in cardiac death (hazard ratio, 0.59; 95% confidence interval, 0.42-0.84; P<0.001), and 41% reduction in ventricular arrhythmias or sudden cardiac death (hazard ratio, 0.59; 95% confidence interval, 0.49-0.70; P<0.001). These more favorable responses to CRT in women were consistently associated with greater echocardiographic evidence of reverse cardiac remodeling in women than in men. CONCLUSIONS: Women obtained greater reductions in the risk of death from any cause, cardiac cause, death or hospitalization for heart failure, and ventricular arrhythmias or sudden cardiac death with CRT therapy compared with men, with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men. Further studies are needed to investigate the exact reasons for these results and determine whether indications for CRT in women should be different from men.

Effects of Nardostachys chinensis on spontaneous ventricular arrhythmias in rats with acute myocardial infarction.

OBJECTIVES: To investigate the effects and mechanisms of Nardostachys chinensis (NC) on spontaneous ventricular arrhythmias in rats with hyper-acute myocardial infarction (AMI). METHODS: Seventy-two rats were randomly divided into the control group (n = 24), metoprolol group (n = 24), and the NC group (n = 24). Premature ventricular contractions (PVCs), ventricular tachycardias (VTs), ventricular fibrillations (VFs), and blood pressure were monitored for 4 hours after coronary artery ligation. The connexin 43 (Cx43) expression in ventricular myocardium was measured by immunohistochemistry, Western blot, and real-time RT-PCR. RESULTS: Compared with the control, metoprolol and NC decreased the VF incidence (50% vs. 4.2%, P < 0.001, and 50% vs. 12.5%, P = 0.005, respectively). There was a steady decrease in the cumulative number of PVCs and VTs within 4 hours from ligating in 3 groups. Compared with the control, metoprolol and NC reduced the cumulative number of VTs and PVCs. Compared with control, metoprolol and NC decreased the infarct size of the left ventricular tissue (55.98% ± 6.20% vs. 39.13% ± 4.53%, P < 0.001, and 55.98% ± 6.20% vs. 42.39% ± 3.44%, P < 0.001, respectively). The results from immunohistochemistry, Western blot, and real-time RT-PCR showed that the protein expression of Cx43 in the control group was significantly lower than that in the metoprolol and NC groups in the infarcted zone. CONCLUSIONS: NC decreased the incidence of spontaneous ventricular arrhythmias (especially VF), reduced Cx43 degradation, and improved Cx43 redistribution in myocardial infarcted zone in rats with hyper-AMI. The data of the present study indicated that NC may be a promising drug in the future to prevent patients with AMI from lethal ventricular arrhythmias in prehospital setting.

Manipulative reduction with minimally invasive percutaneous plate osteosynthesis for 60 patients with distal tibiofibular fractures / 中国骨伤

<p><b>OBJECTIVE</b>To explore clinical effects of manipulative reduction with minimally invasive percutaneous plate osteosynthesis in treating distal tibiofibular fractures.</p><p><b>METHODS</b>From 2009 to 2011, 60 patients with distal tibiofibular fractures were treated by manipulative reduction with minimally invasive percutaneous plate osteosynthesis. Among them, there were 32 males and 28 females aged from 14 to 70 years old with an average of 41.22 +/- 2.06. According to AO classification of fractures,5 cases were type A1, 22 cases were type A2,21 cases were type A3 and 12 cases were type C1. Operation time, blood loss,time of callus and fracture healing were observed, Mazur scoring of ankle joint were used to evaluate therapeutic.</p><p><b>RESULTS</b>Fifty-eight incisions were healed at stage I ,and 2 cases were infected at distal tibial. Operation time was with an average of (62.34 +/- 5.66) min ranged 45 to 90 min;blood loss was 30 to 150 ml with an average of (80.57 +/- 5.59) ml;formation of callus appeared from 4 to 12 weeks,with an average of (8.24 +/- 2.06) weeks, and fracture healing time was from 3 to 6 months, with an average of (4.50 +/- 1.13) months. According to Mazur scoring of ankle joint 40 cases got excellent results, 18 good, and 2 fair.</p><p><b>CONCLUSION</b>Manipulative reduction with minimally invasive percutaneous plate osteosynthesis can obtain reliable fixation. It is a good choice of treating distal tibiofibular fractures by protecting blood supply of fractures.</p>

B-type natriuretic peptide and prognosis of end-stage renal disease: a meta-analysis.

BACKGROUND: The prognostic importance of B-type natriuretic peptide (BNP) or N-terminal pro BNP (NT-proBNP) in patients with end-stage renal disease (ESRD) remains controversial. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an unrestricted search from the MEDLINE and EMBASE in all languages that were published between 1966 and Augest2013. Twenty-seven long-term prospective studies met our inclusion criterias. From the pooled analysis, elevated BNP/NT-proBNP was significantly associated with increased all cause mortality [odds ratio (OR), 3.85; 95% CI, 3.11 to 4.75], cardiovascular mortality (OR, 4.05; 95% CI, 2.53 to 6.84), and cardiovascular events (OR, 7.02; 95% CI, 2.21 to 22.33). The funnel plot showed no evidence of publication bias. The corresponding pooled positive and negative likelihood ratio for prediction of all cause mortality were 1.86 (95% CI, 1.66 to 2.08) and 0.48 (95% CI, 0.42 to 0.55), respectively. CONCLUSIONS/SIGNIFICANCE: BNP/NT-proBNP is a promising prognostic tool to risk-stratify the patients with ESRD. Further investigations are warranted to elucidate the specific pathogenic mechanisms and the impact of other potential prognostic factors.

Early repolarization pattern and risk for arrhythmia death: a meta-analysis.

OBJECTIVES: A meta-analysis was performed to determine the risk and incidence rate of arrhythmia death, cardiac death, and all-cause death in the general population with the early repolarization pattern (ERP). BACKGROUND: The ERP has recently been associated with vulnerability to ventricular fibrillation in case-control studies. However, the prognostic significance of the ERP in the general population is controversial. METHODS: Relevant studies published through July 31, 2012, were searched and identified in the MEDLINE and Embase databases. Studies that reported risk ratio estimates with 95% confidence intervals (CIs) for the associations of interest were included. Data were extracted, and summary estimates of association were obtained using a random-effects model. RESULTS: Of the 9 studies included, 3 studies reported on arrhythmia death (31,981 subjects, 1,108 incident cases during 726,741 person-years of follow-up), 6 studies reported on cardiac death (126,583 subjects, 10,010 incident cases during 2,054,674 person-years of follow-up), and 6 studies reported on all-cause death (112,443 subjects, 22,165 incident cases during 2,089,535 person-years of follow-up). The risk ratios of the ERP were 1.70 (95% CI: 1.19 to 2.42; p = 0.003) for arrhythmia death, 0.78 (95% CI: 0.27 to 2.25; p = 0.63) for cardiac death, and 1.06 (95% CI: 0.87 to 1.28; p = 0.57) for all-cause death. The estimated absolute risk differences of subjects with the ERP were 70 cases of arrhythmia death per 100,000 subjects per year. J-point elevation ≥ 0.1 mV in the inferior leads and notching configuration had an increased risk for arrhythmia death in subgroup studies. CONCLUSIONS: The ERP was associated with increased risk and a low to intermediate absolute incidence rate of arrhythmia death. Further study is needed to clarify which subgroups of subjects with the ERP are at higher risk for arrhythmia death.