The XylR/NtrC-type regulator CbsR positively regulates upstream pathway of chlorobenzene degradation in Pandoraea pnomenusa.

AIMS: Pandoraea pnomenusa MCB032 completely degrades chlorobenzene, whose metabolic pathway is encoded by cbs and clc gene clusters. The putative regulatory factors ClcR and CbsR are predicted to regulate the cbs and clc gene clusters. This research aims to understand the function of ClcR and CbsR. METHODS AND RESULTS: RT-PCR analyses demonstrated that the cbsFAaAbAcAdB operon that encodes catabolic pathways for the degradation of chlorobenzene to chlorocatechol is located on an operon. Moreover, the clcABCDE operon is involved in the 3-chlorocatechol pathway. Gene knockout and transcriptional analysis showed that the transcription of the cbsFAaAbAcAdB operon is positively regulated by CbsR, whereas the clcABCDE operon is activated by ClcR. Primer extension analysis was used to locate the transcription start sites of the cbsFAaAbAcAdB and cbsR operons. Electrophoretic mobility shift assay analyses showed that CbsR is bound to the sites in the promoter regions of cbsFAaAbAcAdB and cbsR operons. CONCLUSION: The XylR/NtrC-type regulator CbsR positively regulates the transcription of the cbsFAaAbAcAdB operon encoding the upstream pathway of chlorobenzene catabolism, while the LysR-type regulator ClcR activates the clcABCDE operon encoding the downstream pathway.

Microbial detoxification of 3,5-xylenol via a novel process with sequential methyl oxidation by Rhodococcus sp. CHJ602.

The compound 3,5-xylenol is an essential precursor used in pesticides and industrial intermediate in the disinfectants and preservatives industry. Its widespread application makes it an important source of pollution. Microbial bioremediation is more environmentally friendly than the physicochemical treatment process for removing alkylphenols from a polluted environment. However, the 3,5-xylenol-degrading bacteria is unavailable, and its degradation mechanism remains unclear. Here, a 3,5-xylenol-metabolizing bacterial strain, designated Rhodococcus sp. CHJ602, was isolated using 3,5-xylenol as the sole source of carbon and energy from a wastewater treatment factory. Results showed that strain CHJ602 maintained a high 3,5-xylenol-degrading performance under the conditions of 30.15 °C and pH 7.37. The pathway involved in 3,5-xylenol degradation by strain CHJ602 must be induced by 3,5-xylenol. Based on the identification of intermediate metabolites and enzyme activities, this bacterium could oxidize 3,5-xylenol by a novel metabolic pathway. One methyl oxidation converted 3,5-xylenol to 3-hydroxymethyl-5-methylphenol, 3-hydroxy-5-methyl benzaldehyde, and 3-hydroxy-5-methylbenzoate. After that, another methyl oxidation is converted to 5-hydroxyisophthalicate, which is metabolized by the protocatechuate pathway. It is catalyzed by a series of enzymes in strain CHJ602. In addition, toxicity bioassay result indicates that 3,5-xylenol is toxic to zebrafish and Rhodococcus sp. CHJ602 could eliminate 3,5-xylenol in water to protect zebrafish from its toxicity. The results provide insights into the bioremediation of wastewater contaminated 3,5-xylenol.

Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Antithrombotic therapy and the risk of new-onset dementia in elderly patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of dementia. Little is known about the relationship of antithrombotic therapy and the risk of dementia in patients with AF without clinical stroke. METHOD: This was an observational study based on a hospital AF registry. Patients aged 65-85 years at the time of AF diagnosis were identified via the computerised database of the clinical management system. Patients with prior stroke or known cognitive dysfunction were excluded. The primary outcome was newly diagnosed dementia during the follow-up period. RESULTS: 3284 patients (mean age 76.4±5.3 years, 51.6% male) were included for analysis. The mean CHA2DS2-VASc score was 3.94±1.44. 18.5% patients were prescribed warfarin, 39.8% were prescribed aspirin and 41.7% were prescribed no antithrombotic therapy. After a mean follow-up of 3.6 years, 71 patients (2.2%) developed dementia, giving rise to an incidence of 0.61%/year. The incidence of dementia were 1.04%/year, 0.69%/year and 0.14%/year for patients on no therapy, aspirin and warfarin, respectively. Both univariate and multivariate analyses showed that age ≥75 years, female gender and high CHA2DS2-VASc score were associated with significantly higher risk of dementia; warfarin use was associated with significantly lower risk of dementia (HR: 0.14%, 95% CI 0.05 to 0.36, p<0.001). Patients on warfarin with time in therapeutic range (TTR) ≥65% had a non-significant trend towards a lower risk of dementia compared with those with TTR <65%. CONCLUSION: In elderly AF patients, warfarin therapy was associated with a significantly lower risk of new-onset dementia compared those with no therapy or aspirin.

Body volume is the major determinant of worsening renal function in acutely decompensated heart failure with reduced left ventricular ejection fraction.

AIMS: Little is known about the relative importance of body volume and haemodynamic parameters in the development of worsening of renal function in acutely decompensated heart failure (ADHF). To study the relationship between haemodynamic parameters, body water content and worsening of renal function in patients with heart failure with reduced ejection fraction (HFrEF) hospitalised for ADHF. METHODS AND RESULTS: This prospective observational study involved 51 consecutive patients with HFrEF (age: 73±14 years, male: 60%, left ventricular ejection fraction: 33.3%±9.9%) hospitalised for ADHF. Echocardiographic-determined haemodynamic parameters and body volume determined using a bioelectric impedance analyser were serially obtained. All patients received intravenous furosemide 160 mg/day for 3 days. There was a mean weight loss of 3.95±2.82 kg (p<0.01), and brain natriuretic peptide (BNP) reduced from 1380±901 pg/mL to 797±738 pg/mL (p<0.01). Nonetheless serum creatinine (SCr) increased from 134±46 µmol/L to 151±53 µmol/L (p<0.01), and 35% of patients developed worsening of renal function. The change in SCr was positively correlated with age (r=0.34, p=0.017); and negatively with the ratio of extracellular water to total body water, a parameter of body volume status (r=-0.58, p<0.001); E:E' ratio (r=-0.36, p=0.01); right ventricular systolic pressure (r=-0.40, p=0.009); and BNP (r=-0.40, p=0.004). Counterintuitively, no correlation was observed between SCr and cardiac output, or total peripheral vascular resistance. Regression analysis revealed that normal body volume and lower BNP independently predicted worsening of renal function. CONCLUSIONS: Normal body volume and lower serum BNP on admission were associated with worsening of renal function in patients with HFrEF hospitalised for ADHF.

Igf3 is essential for ovary differentiation in zebrafish†.

Zebrafish gonadal sexual differentiation is an important but poorly understood subject. Previously, we have identified a novel insulin-like growth factor (Igf) named insulin-like growth factor 3 (Igf3) in teleosts. The importance of Igf3 in oocyte maturation and ovulation has been recently demonstrated by us in zebrafish. In this study, we have further found the essential role of Igf3 in gonadal sexual differentiation of zebrafish. A differential expression pattern of igf3 between ovary and testis during sex differentiation (higher level in ovary than in testis) was found in zebrafish. An igf3 knockout zebrafish line was established using TALENs-mediated gene knockout technique. Intriguingly, all igf3 homozygous mutants were males due to the female-to-male sex reversal occurred during sex differentiation. Further analysis showed that Igf3 did not seem to affect the formation of so-called juvenile ovary and oocyte-like germ cells. Oocyte development was arrested at primary growth stage, and the ovary was gradually sex-reversed to testis before 60 day post fertilization (dpf). Such sex reversal was likely due to decreased germ cell proliferation by suppressing PI3K/Akt pathway in early ovaries of igf3 mutants. Estrogen is considered as a master regulator in fish sex differentiation. Here, we found that igf3 expression could be upregulated by estrogen in early stages of ovarian follicles as evidenced in in vitro treatment assays and cyp19a1a mutant zebrafish, and E2 failed to rescue the defects of igf3 mutants in ovarian development, suggesting that Igf3 may serve as a downstream factor of estrogen signaling in sex differentiation. Taken together, we demonstrated that Igf3 is essential for ovary differentiation in zebrafish.

Point-of-care ultrasound augments physical examination learning by undergraduate medical students.

BACKGROUND: Little is known about the impact of the provision of handheld point-of-care ultrasound (POCUS) devices on physical examination skills of medical students. METHODS: We describe an educational initiative that comprised a POCUS workshop followed by allocation of a POCUS device to medical students for use over the subsequent 8 weeks. They were encouraged to scan patients and correlate their physical examination findings. A mobile instant messaging group discussion platform was set to provide feedback from instructors. Physical examination skills were assessed by means of clinical examination. RESULTS: 210 final-year medical students from the University of Hong Kong participated in the programme. 46.3% completed the end of programme electronic survey: 74.6% enjoyed using the POCUS device, 50.0% found POCUS useful to validate physical examination findings and 47.7% agreed that POCUS increased their confidence with physical examination. 93.9% agreed that the programme should be incorporated into the medical curriculum and 81.9% would prefer keeping the device for longer time from 16 weeks (45.6%) to over 49 weeks (35.3%). Medical students who participated in the POCUS programme had a higher mean score for abdominal examination compared with those from the previous academic year with no POCUS programme (3.65±0.52 vs 3.21±0.80, p=0.014), but there was no statistically significant difference in their mean score for cardiovascular examination (3.62±0.64 vs 3.36±0.93, p=0.203). CONCLUSION: The POCUS programme that included provision of a personal handheld POCUS device improved students' attitude, confidence and ability to perform a physical examination.

Revisiting the Stokes-Einstein relation for glass-forming melts.

Molecular dynamics simulations of Ni36Zr64, Cu65Zr35 and Ni80Al20 were carried out over a broad range of temperature (900-3000 K) to investigate the Stokes-Einstein (SE) relation for glass-forming melts. Our results reproduce experimental structural and transport properties. Results show that the breakdown temperature of the SE relation (TSE) equals the dynamical crossover temperature (TA) and both are roughly twice the glass-transition temperature (Tg) for the three glass-forming melts (TSE = TA ≈ 2.0Tg). The product of the individual component self-diffusion coefficient and viscosity Dαη can be roughly regarded as a constant at the transition zone (a small temperature range around TSE) in which the temperature behaviors of self-diffusion coefficient and viscosity switch from high-temperature Arrhenius to a low-temperature VFT behavior. Below TSE, the decoupling of component diffusion coefficients was found. In particular, the decoupling of component diffusion coefficients can be ascribed to the decoupling of the partial pair structural correlation of components, which can be clearly reflected by the intersection of the high-temperature and low-temperature behaviors of the ratio between the partial pair correlation entropy of components (Sß2/Sα2). Furthermore, the ratio between the partial pair correlation entropy of components may be used to predict the validity of the SE relation, in the absence of both transport coefficients and atomic coordinates.

Zinc mediates the action of androgen in acting as a downstream effector of luteinizing hormone on oocyte maturation in zebrafish†.

The role of androgenic steroids on ovarian development has attracted much attention in recent years, but the molecular mechanism is still largely unknown. In this study, using zebrafish as a model, we found that the trace metal zinc mediates the action of androgen on oocyte maturation. The ovarian and serum testosterone is transiently stimulated by LH during oocyte maturation. Testosterone could mimic the action of LH on oocyte maturation, and its action appears to be independent of the classical nuclear androgen receptor. Consistent with a recent finding that a zinc transporter (Zip9) has been suggested as a novel androgen receptor, we found the labile zinc concentration could be induced by testosterone in the ovarian follicular cells, and zinc could mimic the action of testosterone on oocyte maturation and signaling. Moreover, the action of testosterone on oocyte maturation could be abolished by the chelation of zinc. Thus, the evidence supports the notion that zinc could mediate the action of androgen on oocyte maturation in zebrafish. This finding would shed light on understanding the role of androgen in ovary development and the molecular mechanism of oocyte maturation in fish.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention of Recurrent Cardiovascular Events in a Real-World Cohort of Post-Acute Myocardial Infarction Patients.

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

TIMI risk score for secondary prevention of recurrent cardiovascular events in a real-world cohort of post-non-ST-elevation myocardial infarction patients.

BACKGROUND: Patients who survive non-ST-elevation myocardial infarction (NSTEMI) are at heightened risk of recurrent cardiovascular events. Data on long-term secondary atherothrombotic risk stratification are limited. OBJECTIVES: To stratify post-NSTEMI patients for risk of recurrent cardiovascular events to maximise benefit from aggressive secondary prevention strategies using the TIMI Risk Score for Secondary Prevention (TRS 2°P) score in a real-world cohort of NSTEMI patients. METHODS AND RESULTS: This was a single-centre observational study of 891 post-NSTEMI patients (73.7 ± 12.7 years; male: 54.2%). The TRS 2°P is a nine-point risk stratification tool to predict cardiovascular events in patients with established cardiovascular disease. The primary outcome was a composite endpoint of cardiovascular death, non-fatal MI and non-fatal ischaemic stroke. After a median follow-up of 31 months (IQR: 11.4 - 60.2), 281 patients (31.5%) had developed a primary outcome (13.3%/year) including 196 cardiovascular deaths, 94 non-fatal MIs and 22 non-fatal strokes. The TRS 2°P score was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P score =0 was 1.6%, and increased progressively to 47.4% for those with a TRS 2°P score ≥6 (HR: 20.18, 95% CI: 4.85 to 84.05, p<0.001). Similar associations were also observed between the TRS 2°P score and cardiovascular death and MI (fatal and non-fatal), but not non-fatal ischaemic stroke. CONCLUSION: The TRS 2°P score stratified post-NSTEMI patients for risk of future cardiovascular events and potentially help guide the selection of more aggressive secondary prevention therapy.

Impact of provision of time in therapeutic range value on anticoagulation management in atrial fibrillation patients on warfarin.

INTRODUCTION: The importance of time in therapeutic range (TTR) in patients prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF) cannot be overemphasised. AIM: To evaluate the impact of provision of TTR results during clinic visits on anticoagulation management. DESIGN: Single-centred, randomised controlled study. SETTING: Fifteen arrhythmia clinics in Hong Kong. PATIENTS: AF patients prescribed warfarin. INTERVENTIONS: Provision of TTR or no provision of TTR. MAIN OUTCOME MEASURES: A documented discussion between doctors and patients about switching warfarin to a non-vitamin K oral anticoagulant (NOAC). RESULTS: Four hundred and eighty one patients with AF prescribed warfarin were randomly assigned to (1) a TTR provision group or (2) control. Their mean age was 73.6±12.0 years and 60.7% were men. The mean CHA2DS2-VASc score was 3.2±1.6 and the mean HASBLED score was 1.7±1.2. The mean TTR was 63.9%±29.9%. At the index clinic visit, 71 of 481 patients (14.8%) had a documented discussion about switching warfarin to a NOAC. Patients with provision of TTR results were more likely to discuss switching warfarin to a NOAC than controls (19.1% vs 10.6%, P=0.03), especially those with a TTR <65% (35.2% vs 10.6%, P<0.001). A higher proportion of patients with provision of TTR results switched to a NOAC (5.9% vs 4.1%, P=0.49). CONCLUSIONS: The provision of TTR among patients on warfarin was associated with a discussion about switching from warfarin to a NOAC in those with TTR <65%, but did not result in actual switching to a NOAC, suggesting additional barriers.

Laser cooling of the OH- molecular anion in a theoretical investigation.

The schemes for laser cooling of the OH- anion are proposed using an ab initio method. Scalar relativistic corrections are considered using the Douglas-Kroll Hamilton. Spin-orbit coupling (SOC) effects are taken into account at the MRCI+Q level. SOC effects play important roles in the transition properties of the OH- anion. Transition strengths for the transition of the OH- anion cannot be ignored. Large vibrational branching ratios for the and transitions are determined. Short spontaneous radiative lifetimes for the a3Π1 and A1Π1 states are also predicted for rapid laser cooling. The vibrational branching loss ratio to the intervening states a3Π0 and a3Π1 for the transition is small enough to enable the building of a laser cooling project. The three required laser wavelengths for the and transitions are all in the visible region. The results imply the probability of laser cooling of the OH- anion via both a spin-forbidden transition and a three-electronic-level transition.

Clinical Characteristics, Management, and Outcomes of Hospitalized Heart Failure in a Chinese Population-The Hong Kong Heart Failure Registry.

BACKGROUND: Epidemiological data for heart failure (HF) in the Chinese population is scarce. In this study, we described the clinical characteristics and outcomes of new-onset HF in our population. METHODS AND RESULTS: We conducted a retrospective, observational study on consecutive Chinese patients hospitalized for new-onset HF between 2005 and 2012 in our center. A total of 1940 patients (mean age, 78.2 ± 11.8 years, 54.2% female) were identified. The rate of new HF hospitalization was 0.59 per 1000 population. The most prevalent comorbidities were hypertension (69.8%) and coronary artery disease (29.3%), and 52.3% had HF with preserved ejection fraction (HFpEF). The all-cause mortality was 19.5% at 1 year, 32.1% at 2 years, and 54% at 5 years. Cardiovascular mortality was 7.2% at 1 year, 11.8% at 2 years, and 20.7% at 5 years. No difference in all-cause mortality or cardiovascular mortality was observed between those with HF with reduced ejection fraction than HFpEF. CONCLUSIONS: Our patients with new-onset HF shared similar clinical characteristics with the Caucasian population. The prognosis was poor with high all-cause mortality for both HFpEF and HF with reduced ejection fraction.

Ischaemic stroke in patients with atrial fibrillation with chronic kidney disease undergoing peritoneal dialysis.

AIMS: Little is known about the ischaemic stroke risk and benefit of warfarin therapy for stroke prevention in chronic kidney disease (CKD) patients on peritoneal dialysis (PD) with concomitant atrial fibrillation (AF). Our objective was to determine the risk of ischaemic stroke in a 'real-world' cohort of PD patients with AF, and clinical benefit or harm of aspirin and warfarin. METHODS AND RESULTS: This is a single-centred observational study of Chinese patients with non-valvular AF. Hospitalizations with ischaemic stroke and intracranial haemorrhage (ICH) were recorded. Of 9810 patients from a hospital-based AF registry, 271 CKD patients on PD with AF (76.8 ± 12.5 years, CHA2DS2-VASc: 3.69 ± 1.83, and HAS-BLED: 2.07 ± 0.97) were identified. Amongst these PD patients, 24.7% received warfarin; 31.7% received aspirin; and 43.5% received no antithrombotic therapy. Amongst patients with no antithrombotic therapy, annual incidence of ischaemic stroke in PD patients was comparable with those non-CKD counterparts (9.32 vs. 9.30%/year). Similar to non-CKD patients, annual incidence of ischaemic stroke increased with increasing CHA2DS2-VASc score (CHA2DS2-VASc = 0-1: 5.76 vs. 5.70%/year, P = 1.00; and CHA2DS2-VASc ≥ 2: 10.80 vs. 9.94%/year, P = 0.78). Amongst PD patients, warfarin therapy was associated with lower risk of ischaemic stroke compared with aspirin [Hazard ratio (HR): 0.16, 95% confidence interval (CI): 0.04-0.66, P = 0.01] and no therapy (HR: 0.19, 95% CI: 0.06-0.65, P = 0.01), but not associated with a higher risk of ICH. CONCLUSION: In CKD patients on PD with AF, who had similar ischaemic stroke risk as non-CKD counterparts, warfarin therapy is associated with reduction in risk of ischaemic stroke without a higher risk of ICH.

Laser cooling of BeCl and BeBr molecules in an ab initio method.

In this study, the feasibility of laser-cooling of BeCl and BeBr molecules is studied using ab initio quantum chemistry. The potential energy curves for the X(2)Σ(+), A(2)Π, and 2(2)Π electronic states of BeCl and BeBr are plotted based on multi-reference configuration interaction plus Davidson corrections (MRCI + Q), and the spin-orbit coupling (SOC) effects are considered at the MRCI + Q level. The calculated spectroscopic parameters agree with the experimental data. Highly diagonally distributed Franck-Condon factors are determined for the A(2)Π(ν' = 0) ← X(2)Σ(+)(ν'' = 0) transition: f00(BeCl) = 0.947 and f00(BeBr) = 0.966. Moreover, the suitable radiative lifetimes τ of the A(2)Π(ν' = 0) state are determined for rapid laser cooling: τ(BeCl) = 18.38 ns and τ(BeBr) = 27.09 ns. The proposed cooling wavelengths of both BeCl and BeBr are within the ultraviolet region at λ00(BeCl) = 358.51 nm and λ00(BeBr) = 379.38 nm. Laser cooling schemes for BeCl and BeBr molecules are also developed in consideration of the SOC effects. These results indicate that the inclusion of SOC effects does not affect the judgment of the feasibility of laser cooling of BeCl and BeBr molecules, even for the given BeBr molecules in which the SOC effect is significant.

Ivabradine in Severe Aortic Stenosis with Poor Left Ventricular Ejection Fraction.

Patients with severe aortic stenosis (AS) and left ventricular systolic dysfunction pose a significant challenge to the managing physician. Conventional pharmacological therapy for systolic heart failure has not been proven beneficial in this setting. Ivabradine, a selective current inhibitor, decreases the spontaneous firing rate of sinoatrial nodal cells, thereby reducing the heart rate, and has been shown to reduce a composite end-point of heart failure hospitalization and mortality in patients with impaired left ventricular function. Herein are reported details of the hemodynamic effects and clinical outcome of ivabradine treatment in an 86-year-old man with severe AS and severe left ventricular systolic function.

[Assessments of carotid adventitial remodeling in metabolic syndrome patients using high-frequency ultrasound].

OBJECTIVE: To evaluate the changes of carotid adventitial thickness (AT) and intima media thickness (IMT) and their relationship in metabolic syndrome (MS) patients using high-frequency ultrasound. METHODS: The values of mean AT and mean IMT were measured and calculated for 161 MS patients and compared them with 94 age and gender-matched controls as determined by high-frequency ultrasound between 2009-2011. And 161 patients were divided further into 2 groups of MS with plaque (MS-P, n = 70) and MS without plaque (MS-NP, n = 91). RESULTS: MS-P and MS-NP patients had significantly higher values of mean IMT and carotid artery wall thickness than controls and MS-P patients had significantly higher values of mean AT than controls ((0.77 ± 0.13) mm vs (0.66 ± 0.11) mm, P < 0.01). Moreover, MS-P patients had significantly higher values of mean IMT ((0.98 ± 0.20) mm vs (0.76 ± 0.10) mm, P < 0.01), mean AT ((0.77 ± 0.13) vs (0.69 ± 0.13) mm, P < 0.01) and carotid artery wall thickness ((1.61 ± 0.16)mm vs (1.42 ± 0.09) mm, P = 0.002) than MS-NP patients. And mean AT was positively correlated with mean IMT in controls,MS-P and MS-NP patients (r = 0.603, P < 0.01, r = 0.325, P = 0.005 and r = 0.344, P = 0.004 separately). CONCLUSION: For IMT and AT in MS patients with and without plaques, adventitia participates in vascular remodeling and may be distinguished by high-frequency ultrasound.

Refinement of ischemic stroke risk in patients with atrial fibrillation and CHA2 DS2 -VASc score of 1.

BACKGROUND: Patients with atrial fibrillation (AF) with CHA2 DS2 -VASc score of 1 (where CHA2 DS2 -VASc is CHA2 DS2 -Vascular disease, Age 65-74 years, Sex category) are recommended to receive antithrombotic therapy. Nonetheless, it remains unclear whether individual components that constitute CHA2 DS2 -VASc score contribute equally to the ischemic stroke risk, particularly in patients with CHA2 DS2 -VASc score of 1. The objective was to describe and compare the risk of ischemic stroke of the six individual components constituting CHA2 DS2 -VASc among AF patients with CHA2 DS2 -VASc score of 1. METHODS AND RESULTS: We studied all patients with CHA2 DS2 -VASc score of 1 and no antithrombotic therapy from our cohort of 9,727 Chinese AF patients. A total of 548 patients were studied: 190 patients with CHA2 DS2 -VASc score of 0 and 358 patients with CHA2 DS2 -VASc score of 1. Of those with a baseline CHA2 DS2 -VASc score of 1, 51.1% patients aged 65-75; 29.3% patients were female; 12.0% had hypertension; 4.5% had heart failure; 2.5% had diabetes; and 0.6% had vascular disease. After 1,758 patient-years of follow-up, the annual incidence of stroke was 2.4% and 6.6% for patients with CHA2 DS2 -VASc score of 0 and 1, respectively. Compared with patients with CHA2 DS2 -VASc score of 0, patients with hypertension leading to CHA2 DS2 -VASc score of 1 were at the highest risk of stroke (Hazard ratio [HR]: 9.8, 95% confidence interval [CI]: 2.7-35.6), followed by patients aged 65-74 (HR: 3.9, 95% CI: 2.3-6.6) and female gender (HR: 2.3, 95% CI: 1.1-4.8). Heart failure, diabetes mellitus, and vascular disease were not associated with stroke. CONCLUSION: In AF patients with CHA2 DS2 -VASc score of 1, hypertension confers the highest risk for stroke among other risk factors comprising the score. A more aggressive thromboprophylaxis strategy may be justified among AF patients with CHA2 DS2 -VASc score of 1 due to hypertension.

Transport coefficients and entropy-scaling law in liquid iron up to Earth-core pressures.

Molecular dynamics simulations were applied to study the structural and transport properties, including the pair distribution function, the structure factor, the pair correlation entropy, self-diffusion coefficient, and viscosity, of liquid iron under high temperature and high pressure conditions. Our calculated results reproduced experimentally determined structure factors of liquid iron, and the calculated self-diffusion coefficients and viscosity agree well with previous simulation results. We show that there is a moderate increase of self-diffusion coefficients and viscosity along the melting curve up to the Earth-core pressure. Furthermore, the temperature dependencies of the pair correlation entropy, self-diffusion, and viscosity under high pressure condition have been investigated. Our results suggest that the temperature dependence of the pair correlation entropy is well described by T(-1) scaling, while the Arrhenius law well describes the temperature dependencies of self-diffusion coefficients and viscosity under high pressure. In particular, we find that the entropy-scaling laws, proposed by Rosenfeld [Phys. Rev. A 15, 2545 (1977)] and Dzugutov [Nature (London) 381, 137 (1996)] for self-diffusion coefficients and viscosity in liquid metals under ambient pressure, still hold well for liquid iron under high temperature and high pressure conditions. Using the entropy-scaling laws, we can obtain transport properties from structural properties under high pressure and high temperature conditions. The results provide a useful ingredient in understanding transport properties of planet's cores.