Towards a Rapid-Turnaround Low-Depth Unbiased Metagenomics Sequencing Workflow on the Illumina Platforms.

Unbiased metagenomic sequencing is conceptually well-suited for first-line diagnosis as all known and unknown infectious entities can be detected, but costs, turnaround time and human background reads in complex biofluids, such as plasma, hinder widespread deployment. Separate preparations of DNA and RNA also increases costs. In this study, we developed a rapid unbiased metagenomics next-generation sequencing (mNGS) workflow with a human background depletion method (HostEL) and a combined DNA/RNA library preparation kit (AmpRE) to address this issue. We enriched and detected bacterial and fungal standards spiked in plasma at physiological levels with low-depth sequencing (<1 million reads) for analytical validation. Clinical validation also showed 93% of plasma samples agreed with the clinical diagnostic test results when the diagnostic qPCR had a Ct < 33. The effect of different sequencing times was evaluated with the 19 h iSeq 100 paired end run, a more clinically palatable simulated iSeq 100 truncated run and the rapid 7 h MiniSeq platform. Our results demonstrate the ability to detect both DNA and RNA pathogens with low-depth sequencing and that iSeq 100 and MiniSeq platforms are compatible with unbiased low-depth metagenomics identification with the HostEL and AmpRE workflow.

Determination of (-)-epigallocatechin-3-gallate octaacetate and its metabolites in plasma of rats for pharmacokinetic study by ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry.

(-)-Epigallocatechin-gallate octaacetate (pro-EGCG), a prodrug of epigallocatechin-gallate (EGCG), has been used for pre-clinical study for the treatment of endometriosis. A validated analytical method has been developed for the determination of plasma pro-EGCG and its metabolites after oral administration using ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry (UPLC-Qtof-MS). This method is more robust, rapid, sensitive, simpler, and able to detect pro-EGCG metabolites compared to our previous method. Pro-EGCG in the plasma was stabilized from rapid degradation by formic acid, extracted by isopropanol/methyl-tert-butyl ether mixture, separated by UPLC core column, and quantified by an exact mass method with Qtof-MS. The lower limit of quantification (LLOQ), intra-day and inter-day precision, and accuracy for the range of 0.01-2.5 µg/mL were within acceptable limits. The sensitivity was improved by 25 folds using pro-EGCG ammonium adduct [M + NH4]+. This is the first report on the pharmacokinetics of oral administration with maximum-concentration (Cmax) was 0.067 ± 0.04 µg/mL, time-of-maximum-concentration (Tmax) was 1.33 h, area-under-curve (AUC) was 0.20 ± 0.05 h × µg/mL, and elimination-rate was 0.20 ± 0.11 hr-1. The pharmacokinetic profiles of pro-EGCG metabolites, (-)-epigallocatechin-gallate (EGCG) diacetates and EGCG triacetates, were also presented. This method is robust, rapid, and sensitive for the pharmacokinetic study of pro-EGCG and metabolites.

Adverse 30-Day Clinical Outcomes and Long-Term Mortality Among Patients With Preprocedural Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: Approximately 5-10% of patients presenting for percutaneous coronary intervention (PCI) have concurrent atrial fibrillation (AF). To what extent AF portends adverse long-term outcomes in these patients remains to be defined. METHODS: We analysed data from the multicentre Melbourne Interventional Group Registry from 2014-2018. Patients were identified as being in AF or sinus rhythm (SR) at the commencement of PCI. The primary endpoint was long-term mortality, obtained via linkage with the National Death Index. RESULTS: 13,286 procedures were included, with 800 (6.0%) patients in AF and 12,486 (94.0%) in SR. Compared to SR, patients with AF were older (72.9±10.9 vs 64.1±12.0 p<0.001) and more likely to have comorbidities including diabetes mellitus (31.3% vs 25.0% p<0.001), hypertension (74.4% vs 65.1% p<0.001) and moderate to severe left ventricular systolic dysfunction (36.6% vs 19.5% p<0.001). Atrial fibrillation was associated with an increased risk of in-hospital mortality (11.0% vs 2.5% p<0.001) and MACE (composite of all-cause mortality, myocardial infarction, or target vessel revascularisation) (11.9% vs 4.2% p<0.001). In-hospital major bleeding was more common in the AF group (3.1% vs 1.0% p<0.001). On Cox proportional hazards modelling, AF was an independent predictor of long-term mortality (adjusted HR 1.38 95% CI 1.11-1.72 p<0.004) at a mean follow-up of 2.3±1.5 years. CONCLUSIONS: Preprocedural AF is common among patients presenting for PCI. Preprocedural AF is associated with high-rates of comorbid illnesses and portends higher risk of short- and long-term outcomes including mortality underscoring the need for careful evaluation of its risks prior to PCI.

Reperfusion Times and Outcomes in Patients With ST-Elevation Myocardial Infarction Presenting Without Pre-Hospital Notification.

BACKGROUND: Primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) is recommended within 90 min of first medical contact. Those without pre-hospital notification (PN) are less likely to meet reperfusion targets and are an understudied subset of the STEMI population. METHODS: An observational cohort study from a multicentre PCI registry of consecutive patients undergoing primary PCI for STEMI between 2012 and 2017. Exclusion criteria included out-of-hospital cardiac arrest, prior thrombolysis, symptom onset >12 h prior, and cardiogenic shock. RESULTS: 2519 patients were included: 1392 (55.3%) without PN (no-PN group) and 1127 (44.7%) with PN (PN group). Those without PN had longer median DTBT (78 min vs 51 min, p < 0.001) and STBT (206 min vs 161 min, p < 0.001), with only 55% meeting DTBT targets out-of-hours in the no-PN group. No-PN patients had lower rates of AHA/ACC type B2/C lesions, GP IIb/IIIa use, aspiration thrombectomy and had smaller stent diameter (all p ≤ 0.003), suggesting smaller areas of ischemic myocardium. There were no significant differences in 30-day MACE (no-PN 5.6% vs PN 6.5%, p = 0.36) or long-term National Death Index linked mortality (no-PN 6.2% vs PN 7.9%, p = 0.09). Lack of PN did not independently predict long-term mortality. CONCLUSION: Despite comparably excellent outcomes overall, those without PN had longer ischemic times and were less likely to meet DTBT targets, especially after hours. Ischemic times may be a better evaluation of PN networks than hard clinical outcomes, and efficient systems of care tailored to the individual health service are essential to ensure timely reperfusion of patients with STEMI.

Safety assessment of polymeric micelles as an ophthalmic drug delivery system for intravitreal administration of dasatinib.

BACKGROUND AND AIMS: Ocular safety/biocompatibility is an essential element of ophthalmic drug delivery. We previously applied poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-b-PCL) micelles to deliver dasatinib for the management of proliferative vitreoretinopathy (PVR) in vitro. Herein, we seek to ascertain the ocular safety/compatibility of blank and dasatinib loaded PEG-b-PCL micelles, which will set the stage for the future in vivo efficacy evaluations and/or clinical translation for PVR or other eye diseases. METHODS: To access the safety of blank and dasatinib loaded micelles, in vitro cell based assays (LDH cell membrane damage test, SRB cytotoxicity, TEER and permeability of RPE tight junctions), in vivo slit lamp biomicroscopy and optical coherence tomography, Ex vivo histology (H&E staining, GFAP immunofluorescence staining and TUNEL assay) were undertaken. RESULTS: Both blank and dasatinib loaded micelles showed remarkable safety profiles at cellular levels. They also caused negligible ocular toxicity/abnormalities up to 28 days post-intravitreal injection in mice. The micelles did not insult the cornea, as demonstrated by slit-lamp biomicroscopy. Ex vivo histology and in vivo optical coherence tomography revealed a normal retinal structure with minimal apoptosis and stresses. CONCLUSION: Taken together, both blank and dasatinib loaded micelles appear to be safe and their applications in drug delivery for eye diseases should be explored.

Effect of Age on Clinical Outcomes in Elderly Patients (>80 Years) Undergoing Percutaneous Coronary Intervention: Insights From a Multi-Centre Australian PCI Registry.

OBJECTIVES: To evaluate the effect of age in an all-comers population undergoing percutaneous coronary intervention (PCI). BACKGROUND: Age is an important consideration in determining appropriateness for invasive cardiac assessment and perceived clinical outcomes. METHODS: We analysed data from 29,012 consecutive patients undergoing PCI in the Melbourne Interventional Group (MIG) registry between 2005 and 2017. 25,730 patients <80 year old (78% male, mean age 62±10 years; non-elderly cohort) were compared to 3,282 patients ≥80 year old (61% male, mean age 84±3 years; elderly cohort). RESULTS: The elderly cohort had greater prevalence of hypertension, diabetes and previous myocardial infarction (all p<0.001). Elderly patients were more likely to present with acute coronary syndromes, left ventricular ejection fraction <45% and chronic kidney disease (p<0.0001). In-hospital, 30-day and long-term all-cause mortality (over a median of 3.6 and 5.1 years for elderly and non-elderly cohorts, respectively) were higher in the elderly cohort (5.2% vs. 1.9%; 6.4% vs. 2.2%; and 43% vs. 14% respectively, all p<0.0001). In multivariate Cox regression analysis, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (HR 3.8, 95% CI: 3.4-4.3), cardiogenic shock (HR 3.0, 95% CI: 2.6-3.4), ejection fraction <30% (HR 2.5, 95% CI: 2.1-2.9); and age ≥80 years (HR 2.8, 95% CI: 2.6-3.1) were independent predictors of long-term all-cause mortality (all p<0.0001). CONCLUSION: The elderly cohort is a high-risk group of patients with increasing age being associated with poorer long-term mortality. Age, thus, should be an important consideration when individualising treatment in elderly patients.

Clinical outcomes following ST-elevation myocardial infarction secondary to stent thrombosis treated by percutaneous coronary intervention.

OBJECTIVES: To assess the clinical outcomes of patients presenting with ST-elevation myocardial infarction (STEMI) secondary to stent thrombosis (ST) compared to those presenting with STEMI secondary to a de novo culprit lesion and treated by percutaneous coronary intervention (PCI). BACKGROUND: ST is an infrequent but serious complication of PCI with substantial associated morbidity and mortality, however with limited data. METHODS: We studied consecutive patients who underwent PCI for STEMI from 2005 to 2013 enrolled prospectively in the Melbourne Interventional Group registry. Patients were divided into two groups: the ST group comprised patients where the STEMI was due to ST and the de novo group formed the remainder of the STEMI cohort and all patients were treated by PCI. The primary endpoint was 30-day all-cause mortality. RESULTS: Compared to the de novo group (n = 3,835), the ST group (n = 128; 3.2% of STEMI) had higher rates of diabetes, hypertension and dyslipidemia, established cardiovascular diseases, myocardial infarction, and peripheral vascular disease, all p < .01. Within the ST group, very-late ST was the most common form of ST, followed by late and early ST (64, 19, and 17%, respectively). There was no significant difference in the primary outcome between the ST group and the de novo group (4.7 vs. 7.1%, p = .29). On multivariate analysis, ST was not an independent predictor of 30-day mortality (odds ratio: 0.62, 95% confidence interval: 0.07-1.09, p = .068). CONCLUSION: The short-term prognosis of patients with STEMI secondary to ST who were treated by PCI was comparable to that of patients with STEMI due to de novo lesions.

Outcomes of cardiogenic shock complicating acute coronary syndromes.

OBJECTIVES: We aimed to assess the outcomes of cardiogenic shock (CS) complicating acute coronary syndromes (ACS). BACKGROUND: CS remains the leading cause of mortality in patients presenting with ACS despite advances in care. METHODS: We studied 13,184 patients undergoing percutaneous coronary intervention (PCI) for all subtypes of ACS enrolled prospectively in a large multicentre Australian registry (Melbourne Interventional Group registry) from 2005 to 2013. All-cause mortality was obtained via linkage to the National Death Index. Patients were divided into those with and those without CS. RESULTS: Compared to the non-CS group (n = 12,548, 95.2%), the CS group (n = 636, 4.8%) had a higher proportion of out-of-hospital cardiac arrest (OHCA) (31.1 vs. 2.2%) and ST-elevation myocardial infarction (STEMI) presentation (89 vs. 34%), both p < .01. Patients in the CS group had higher rates of in-hospital (40.4 vs. 1.2%) and 30-day (41 vs. 1.7%) mortality compared to the non-CS group. Long-term mortality over a median follow-up of 4.2 years was higher in the CS group (50.6 vs. 13.8%), p < .001. Trends of in-hospital and 30-day mortality rates of CS complicating ACS were relatively stable from 2005 to 2013. Predictors of long-term NDI-linked mortality within the CS group include severe left ventricular systolic dysfunction (HR 3.0), glomerular filtration rate (GFR) <30 (HR 2.56), GFR 30-59 (HR 1.94), OHCA (HR 1.46), diabetes (HR 1.44), and age (HR 1.02), all p < .05. CONCLUSIONS: Rates of CS-related mortality complicating ACS have remained very high and steady over nearly a decade despite progress in STEMI systems of care, PCI techniques, and medical therapy.

Impact of lunar phase on outcomes following ST-elevation myocardial infarction.

BACKGROUND: There is a long-held belief in the association between the full moon and extremes of human behaviour and adverse health consequences. Small-scale studies are conflicting; however, most suggest no clear association between lunar phase and occurrence of acute coronary syndromes. AIMS: To evaluate the impact of the lunar phase, and in particular, the full moon phase, on the incidence and outcomes among ST-elevation myocardial infarction (STEMI) cases undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a multi-centre retrospective study from the Melbourne Interventional Group registry, including 7570 STEMI cases from six tertiary centres over a 12-year study period in Victoria, Australia, and performed statistical analysis using Stata software. Primary outcomes studied were the incidence of STEMI, the occurrence of major adverse cardiac and cerebrovascular events and mortality at 1 and 5 years in cases of STEMI undergoing primary or rescue percutaneous coronary intervention during the full moon between 2005 and 2017 in Victoria, Australia. RESULTS: This study demonstrated neither significant difference in STEMI incidence (P = 0.61) nor of major adverse cardiovascular events across all lunar phases. Subgroup analysis confirmed no difference in outcomes during the full moon compared to a composite of other lunar phases.Kaplan-Meier survival estimates showed similar 30-day outcomes across lunar phases (P = 0.35) and when comparing full moon to a composite of other lunar phases (P = 0.45). Similarly, there was no significant difference in survival at 1 and 5 years between lunar phases (P = 0.68) or compared to the full moon phase (P = 0.51). CONCLUSIONS: This study showed no significant difference in the incidence or cardiovascular outcomes and survival in patients with STEMI undergoing primary or rescue percutaneous coronary intervention during the lunar phases.

Oral delivery of paclitaxel by polymeric micelles: A comparison of different block length on uptake, permeability and oral bioavailability.

Drug solubility and permeability are two major challenges affecting oral delivery, the most popular route of drug administration. Polymeric micelles is an emerging technology for overcoming the current oral drug delivery hurdles. Previous study primarily focused on developing new polymers or new micellar systems and a systematic investigation of the impact of the polymer block length on solubility and permeability enhancement; and their subsequent effect on oral bioavailability is lacking. Herein, by using paclitaxel, a poorly soluble P-glycoproteins (P-gp) substrate, as a model, we aim to assess and compare the drug-loaded micelles prepared with two different molecular weight of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL), with the ultimate goal of establishing a strong scientific rationale for proper design of formulations for oral drug delivery. PEG-b-PCL (750:570) (PEG17-b-PCL5) and PEG-b-PCL (5k:10k) (PEG114-b-PCL88) effectively enhanced the solubility of paclitaxel compared to the free drug. PEG-b-PCL (750:570) increased both P-gp and non P-gp substrate cellular uptake and increased the apparent permeability coefficient of a P-gp substrate. In vivo animal study showed that PEG-b-PCL micelles efficiently enhanced the oral bioavailability of paclitaxel. In addition to solubility enhancement, polymer choice also plays a pivotal role in determining the oral bioavailability improvement, probably via permeation enhancement. In conclusion, the knowledge gained in this study enables rational design of polymeric micelles to overcome the current challenges of oral drug delivery and it also provides a basis for future clinical translation of the technology.

Orally-dissolving film for sublingual and buccal delivery of ropinirole.

Ropinirole is a very important treatment option for Parkinson's disease (PD), a major threat to the aging population. However, this drug undergoes extensive first-pass metabolism, resulting in a low oral bioavailability. Moreover, the necessity of frequent administration due to the short half-life of ropinirole may jeopardize patient compliance. Indeed, taking this drug in solid oral dosage forms (e.g. Tablet) can be a challenge because of the tremor, rigidity, limited mobility, and impaired drug absorption experienced by PD patients. In light of these, there is a pressing need to devise formulations for the delivery of ropinirole that allow simple and easy administration and fast drug action, as well as avoidance of first-pass metabolism and overcoming the challenge of impaired absorption due to gastrointestinal dysfunctions, etc. Herein, we seek to overcome all these challenges via sublingual or buccal delivery of orally-dissolving films. Accordingly, we aimed to fabricate and characterize orally-dissolving films of ropinirole and assess their in vivo pharmacokinetics after sublingual and buccal administration. The ropinirole oral film was non-toxic and exhibited fast disintegration and dissolution and was physically stable for at least 28 days. Upon buccal/sublingual administration of the oral films, ropinirole reached the systemic circulation within 15 min and bioavailability was significantly improved, which may be attributable to avoidance of first-pass metabolism via absorption through the oral cavity. In conclusion, our ropinirole oral film improved bioavailability after sublingual or buccal administration. This formulation potentially overcomes biopharmaceutical challenges and provide a convenient means of administration of ropinirole or other anti-PD drugs.

Oligonucleotide-conjugated nanoparticles for targeted drug delivery via scavenger receptors class A: An in vitro assessment for proof-of-concept.

Spherical nucleic acid gold nanoparticles represent a unique nanotechnology in which the spherical arrangement of oligonucleotides enables the nanoparticles to be efficiently internalized into cells expressing scavenger receptors class A (SR-A). Herein, we seek to replace the gold core with a biodegradable polymeric construct and explore their potential applications in targeted drug delivery. Oligonucleotide-conjugated poly(ethylene glycol)-block-poly(ε-caprolactone) was synthesized and characterized by 1H NMR and gel electrophoresis. This polymer was applied to fabricate micellar nanoparticles (OLN-NPs) by an anti-solvent method. These nanoparticles have a mean particle size about 58.1nm with a narrow size distribution (PDI <0.2) and they were also non-cytotoxic. Relative to non-targeted NPs, OLN-NPs exhibited substantially better uptake (3.94×) in a mouse endothelial cell line (C166), attributing to lipid-raft-mediated endocytosis via SR-A. To explore the potential applications of OLN-NPs as drug carriers, paclitaxel, a poorly soluble anti-angiogenic compound, was selected as the model. OLN-NPs increased the solubility of paclitaxel by at least 300×. The boosted drug solubility in conjunction with improved cellular uptake translated into enhanced in vitro efficacy in the inhibition of angiogenesis. In conclusions, OLN-NPs show considerable promise in targeted drug delivery and their potential applications should be further investigated.

An Eco-Friendly, Tunable and Scalable Method for Producing Porous Functional Nanomaterials Designed Using Molecular Interactions.

Despite significant improvements in the synthesis of templated silica materials, post-synthesis purification remains highly expensive and renders the materials industrially unviable. In this study this issue is addressed for porous bioinspired silica by developing a rapid room-temperature solution method for complete extraction of organic additives. Using elemental analysis and N2 and CO2 adsorption, the ability to both purify and controllably tailor the composition, porosity and surface chemistry of bioinspired silica in a single step is demonstrated. For the first time the extraction is modelled using molecular dynamics, revealing that the removal mechanism is dominated by surface-charge interactions. This is extended to other additive chemistry, leading to a wider applicability of the method to other materials. Finally the environmental benefits of the new method are estimated and compared with previous purification techniques, demonstrating significant improvements in sustainability.

Impact of high-sensitivity cardiac troponin I assays on patients presenting to an emergency department with suspected acute coronary syndrome.

OBJECTIVE: To determine whether introduction of high-sensitivity cardiac troponin I (hscTn-I) assays affected management of patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary referral hospital. DESIGN, PATIENTS AND SETTING: A retrospective analysis of all patients presenting to the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I assays on 23 April 2012. MAIN OUTCOME MEASURES: Hospital admission rates, time spent in the ED, rates of coronary angiography, rates of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosis of ACS, and rates of inhospital mortality. RESULTS: 12 360 consecutive patients presented with suspected ACS during the study period; 1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1 year after the changeover to hscTn-I assays. Comparing the two patient groups, there was no statistically significant difference in all-hospital admission rates (95% CI for the difference, - 3.1% to 0.3%; P = 0.10) or proportion of patients subsequently discharged with a diagnosis of ACS (95% CI for the difference, - 2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the difference, - 0.59 to - 0.43; P < 0.001) and the proportion of admitted patients undergoing coronary angiography was higher (53.4% v 45.2%; 95% CI for the difference, 4.3 to 12.0 percentage points; P < 0.001), but there was no statistically significant rise in the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI for the difference, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from ACS did not change significantly (95% CI for the difference, - 1.5% to 0.8%; P = 0.43). CONCLUSION: The introduction of hscTn-I assays appeared to be associated with more rapid diagnosis, resulting in less time spent in the ED, without a change in hospital admission rates. A higher proportion of patients had coronary angiographies after the changeover, but there was no significant change in rates of invasive treatment or inhospital mortality.

Cardiovascular Protective Effects of Adjunctive Alternative Medicine (Salvia miltiorrhiza and Pueraria lobata) in High-Risk Hypertension.

Introduction. Hypertension in association with diabetes (DM), renal impairment (RI), and left ventricular hypertrophy (LVH) increases the risk of future cardiovascular events. We hypothesize, traditional herbal medicines Danshen and Gegen (D&G) have beneficial effects on atherogenesis in these high-risk hypertensive subjects. Subjects and Methods. 90 asymptomatic hypertensive subjects associated with LVH (63.3%), DM (62.2%), or RI (30%) were randomized to receive D&G herbal capsules 1 gm/day, 2 gm/day, or identical placebo capsules in double-blind and parallel fashion for 12 months. Brachial flow-mediated dilation (endothelium-dependent dilation, FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. All data were analyzed using the Statistical Package for Social Sciences in Windows 16.0. Results. Their mean age was 55 ± 8 years, and 74.4% were male. After 12 months of adjunctive therapies and compared with baseline, there were no significant changes in blood pressure, heart rate, hematological, glucose, and creatinine profiles in both placebo and D&G groups. FMD improved significantly during D&G (P = 0.0001) and less so after placebo treatment (P = 0.001). There was a mild but significant decrease in carotid IMT after D&G (P < 0.001) but no significant changes after placebo. A trend of better improvement in FMD after higher versus lower D&G dosages was seen. D&G were well tolerated, with no significant adverse events or blood biochemistry changes. Conclusion. D&G adjunctive treatment was well tolerated and significantly improved atherogenesis in high-risk hypertensive patients, with potential in primary atherosclerosis prevention.

CO2 sequestration by enzyme immobilized onto bioinspired silica.

We present the first report on bioinspired silica - produced using a green method - supported carbonic anhydrase for carbon capture and demonstrate significantly improved carbon capture efficiency and stability relevant to flue gas temperatures.

Contemporary outcomes in women undergoing percutaneous coronary intervention for acute coronary syndromes.

BACKGROUND: Uncertainty remains as to whether females benefit as much as males from percutaneous coronary intervention (PCI) in the setting of an acute coronary syndrome (ACS). METHODS: We compared 802 women with 2151 men presenting with ACS, undergoing PCI from April 2004 to October 2006 from the Melbourne Interventional Group registry. Clinical characteristics, in-hospital, 30-day and 1-year outcomes were compared. RESULTS: Women were older (69.6 ± 11.6 vs. 62.17 ± 12.3 years, p<0.001), and had more diabetes (27.1% vs. 19.6%, p<0.001) and hypertension (70.3% vs. 53.9%, p<0.001) than men. Women were less likely to present with ST-elevation myocardial infarction (30.5% vs. 37.9%, p<0.001). Bleeding (3.6% vs. 0.8%, p<0.001) was higher among women. Thirty-day mortality (4.7 vs. 2.4%, p<0.001) and MACE (10.1 vs. 6.4%, p<0.001) were higher in women. Gender was an independent predictor of overall MACE at 30 days (OR 1.45, 95% CI 1.04-2.02, p=0.03) but not death. At 12 months, there were no significant differences in mortality (6.4% vs. 4.8%, p=0.09), myocardial infarction (5.5% vs. 5.0%, p=0.64), target vessel revascularization (7.9% vs. 7.0%, p=0.42) and MACE (16.3% vs. 14%, p=0.13) between women and men. CONCLUSIONS: There is an early hazard amongst women undergoing PCI for ACS, but not at 12 months. These data suggest that gender should not affect the decision to offer PCI but further gender specific studies are warranted.

Synthesis of H(x)Li(1-x)LaTiO4 from quantitative solid-state reactions at room temperature.

The layered perovskite HLaTiO(4) reacts stoichiometrically with LiOH.H(2)O at room temperature to give targeted compositions in the series H(x)Li(1-x)LaTiO(4). Remarkably, the Li(+) and H(+) ions are quantitatively exchanged in the solid state and this allows stoichiometric control of ion exchange for the first time in this important series of compounds.

Spontaneous formation of crystalline lithium molybdate from solid reagents at room temperature.

Lithium molybdate has been prepared by grinding LiOH x H(2)O with MoO(3) in air at room temperature. X-Ray powder diffraction data show that the formation of highly crystalline Li(2)MoO(4) is largely complete after 10 min. The phenacite structure of this material is the same as that derived from an X-ray diffraction study of a single crystal obtained from aqueous solution [R3; a = 14.3178(14) A, c = 9.5757(9) A]. Anhydrous lithium hydroxide fails to give the same reaction indicating that the water of crystallisation of LiOH x H(2)O is a vital component in this rapid synthesis. Differential scanning calorimetry measurements show that this reaction can proceed spontaneously between the two stable solid reagents at sub-ambient temperatures and is driven by the liberation of water from the crystalline lattice. Lithium molybdate prepared in this manner has significantly smaller and more regularly shaped particles than samples prepared by other synthetic methods.

Smoking without exception adversely affects vascular structure and function in apparently healthy Chinese: implications in global atherosclerosis prevention.

BACKGROUND: Both active and passive smoking are prevalent in China but cardiovascular diseases were less prevalent in the past. We studied the current relationship between surrogate atherosclerosis markers and smoking in Chinese. METHODS: Endothelium-dependent flow-mediated dilation (FMD) of brachial artery and carotid intima-media thickness (IMT) were measured non-invasively by ultrasound in 616 apparently healthy Chinese (23% smokers), recruited from greater China and the USA. RESULTS: The Chinese smokers had significantly impaired FMD (7.0+/-2.3 vs. 8.2+/-2.5%, p<0.001) and endothelium-independent vasodilation (GTN, 17.4+/-3.9 vs. 18.7+/-4.1%, p=0.001) and thicker IMT (0.61+/-0.13 vs. 0.58+/-0.12 mm, p=0.025). 91% of the smokers were male. Both endothelium-dependent (6.9+/-2.2 vs. 8.0+/-2.5%, p<0.001) and independent (17.3+/-3.5 vs. 18.2+/-3.7%, p=0.047) vasodilation were significantly lower in the male smokers than non-smokers, although their age and cholesterol levels were lower. FMD-to-GTN ratio in the smokers were lower (0.41+/-0.12 vs. 0.45+/-0.13, p=0.005). Multivariate analyses confirmed an independent adverse impact of smoking on vascular functions. There were no consistent interactions between subject location and impact of smoking on FMD and IMT. CONCLUSION: In these apparently healthy native and overseas Chinese subjects, smoking is adversely associated with endothelial dysfunction and arterial wall thickening, with serious implication in atherosclerosis prevention.