Three-dimensional visualization of predatory gastropod feeding teeth with synchrotron scanning.

Several families of neogastropod mollusks independently evolved the ability to drill through mineralized prey skeletons using their own mineralized feeding teeth, sometimes with shell-softening chemical agents produced by an organ in the foot. Teeth with more durable tooth shapes should extend their use and improve predator performance, but past studies have described only the cusped-side of teeth, mostly overlooking morphologies related to functional interactions between teeth. Here, we describe the three-dimensional morphology of the central drilling tooth (rachidian) from four species of the neogastropod family Muricidae using synchrotron tomographic microscopy and assemble a three-dimensional model of a multitooth series in drilling position for two of them to investigate their dynamic form. We find two new types of articulating surfaces, including a saddle joint at either end of the rachidian and a large tongue-and-groove joint in the center. The latter has a shape that maximizes contact surface area between teeth as they rotate away from each other during drilling. Articulating joints have not been described in Neogastropod radula previously, but they are consistent with an earlier hypothesis that impact forces on individual teeth during predatory drilling are dispersed by tooth-tooth interactions.

Photosynthesis and crop productivity are enhanced by glucose-functionalised carbon dots.

From global food security to textile production and biofuels, the demands currently made on plant photosynthetic productivity will continue to increase. Enhancing photosynthesis using designer, green and sustainable materials offers an attractive alternative to current genetic-based strategies and promising work with nanomaterials has recently started to emerge. Here we describe the in planta use of carbon-based nanoparticles produced by low-cost renewable routes that are bioavailable to mature plants. Uptake of these functionalised nanoparticles directly from the soil improves photosynthesis and also increases crop production. We show for the first time that glucose functionalisation enhances nanoparticle uptake, photoprotection and pigment production, unlocking enhanced yields. This was demonstrated in Triticum aestivum 'Apogee' (dwarf bread wheat) and resulted in an 18% increase in grain yield. This establishes the viability of a functional nanomaterial to augment photosynthesis as a route to increased crop productivity.

Using the clinical chemistry score in the emergency department to detect adverse cardiac events: a diagnostic accuracy study.

BACKGROUND: The ability to rule out or in a major adverse cardiac event (MACE) in patients with suspected acute coronary syndrome at emergency department (ED) presentation would be beneficial to patient care and the health care system. The clinical chemistry score (CCS) was evaluated in this context. METHODS: This diagnostic accuracy study evaluated 2 different ED cohorts with suspected acute coronary syndrome. For patients in cohort 1, who presented to the ED of 3 hospitals in Hamilton, Ontario, between May and August 2013, retrospective measurements were taken using the Ortho Clinical Diagnostics high-sensitivity cardiac troponin I (hs-cTnI) assay; for patients in cohort 2, who presented to the ED of the same 3 hospitals in Hamilton between November 2012 and February 2013, an ED cardiac presentation blood test panel was performed with the Abbott Diagnostics hs-cTnI assay. The sensitivity and specificity of the CCS (cut-offs of ≥ 1 and 5) and hs-cTnI alone (published cut-offs) were compared for MACE (composite of death, myocardial infarction, unstable angina, revascularization) at 30 days for both cohorts and at 90 days for cohort 2. RESULTS: The incidence of MACE at 30 days was higher in cohort 1 (n = 1058) (19.4%, 95% confidence interval [CI] 16.8%-22.2%) than in cohort 2 (n = 5974) (14.6%, 95% CI 13.6%-15.6%). In cohort 1, a CCS of 1 or above yielded a sensitivity of 99.5% (95% CI 97.3%-99.9%). The sensitivity with an Ortho hs-cTnI cut-off of 1 ng/L or above was 91.2% (95% CI 86.5%-95.7%). The specificity of a CCS of 5 (97.8%, 95% CI 96.5%-98.7%) was higher than when the overall 99th-percentile cut-off for the Ortho hs-cTnI assay (> 11 ng/L; 90.1%, 95% CI 87.9%-92.0%) was used. A similar pattern was observed in cohort 2 at 30 days and persisted at 90 days with the Abbott hs-cTnI assay. INTERPRETATION: The CCS derived with 2 different hs-cTnI assays and ED populations yielded higher sensitivity and specificity estimates for MACE than hs-cTnI alone. An intervention study is needed to evaluate the impact of the CCS at both the patient and hospital levels. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01994577.

Comparison of two biomarker only algorithms for early risk stratification in patients with suspected acute coronary syndrome.

BACKGROUND: We developed a biomarker algorithm encompassing the clinical chemistry score (CCS; which includes the combination of a random glucose concentration, an estimated glomerular filtration rate and high-sensitivity cardiac troponin; hs-cTn) with the Ortho Clinical Diagnostics hs-cTnI assay (CCS-serial) and compared it to the cutoffs derived from Ortho Clinical Diagnostics 0/1 h (h) algorithm for 7-day myocardial infarction (MI) or cardiovascular (CV)-death. METHODS: The study cohort was an emergency department (ED) population (n = 906) with symptoms suggestive of acute coronary syndrome (ACS) who had two Ortho hs-cTnI results approximately 3 h apart. Diagnostic parameters (sensitivity/specificity/negative predictive value; NPV/positive predictive value; PPV) were derived for the CCS-serial and the 0/1 h algorithm for 7-day MI/CV-death. A safety analysis was performed for patients in the rule-out arms of the algorithms for 30-day MI/death. RESULTS: The CCS-serial algorithm yielded 100% sensitivity/NPV (32% low-risk) and 95.7% specificity/65% PPV (11% high-risk). The 0/1 h algorithm-cutoffs yielded sensitivity/NPV/specificity/PPV of 97.8%/99.4%/91.3%/50%, which classified 38% of patients as low-risk and 16% of patients as high-risk. Four patients (1.2%) in the 0/1 h algorithm-cutoff rule-out arm had a 30-day MI/death outcome as compared to zero patients in the CCS-serial rule-out arm (p = 0.06). CONCLUSION: Both the CCS-serial and 0/1 h algorithm cutoffs yield high NPVs with a similar proportion of patients identified as low-risk. These data may be useful for sites who are unable to collect samples at 0/1 h in the emergency department.

Clinical evaluation of Ortho Clinical Diagnostics high-sensitivity cardiac Troponin I assay in patients with symptoms suggestive of acute coronary syndrome.

BACKGROUND: As more companies obtain regulatory approval for high-sensitivity cardiac troponin (hs-cTn) assays there is an urgent need for independent analytical and clinical evaluations. To this end, we have evaluated Ortho Clinical Diagnostics' hs-cTnI assay and compared it to their contemporary cTnI-ES assay in emergency department (ED) patients with suspected acute coronary syndrome (ACS). METHODS: The study cohort consisted of ED patients (n = 906) with symptoms suggestive of ACS who had Ortho hs-cTnI and cTnI-ES results at presentation and 3 h (with calculated delta (0-3 h) defined as the absolute concentration difference between paired results). The primary composite outcome was 7-day myocardial infarction (MI) or cardiovascular death, with secondary analyses performed for 7-day MI and index-MI. Analytical imprecision testing (i.e., coefficient of variation; CV), receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC), and diagnostic parameters (sensitivity/specificity/predictive values) were calculated. RESULTS: The hs-cTnI assay had superior precision compared to the cTnI-ES assay below 5 ng/L in EDTA plasma (hs-cTnI CV ≤ 15% versus cTnI-ES CV ≥ 85%). The AUCs were higher for hs-cTnI as compared to cTnI-ES at 0 h (0.88 vs. 0.85), 3 h (0.94 vs. 0.92), and the delta (0-3 h) value (0.91 vs. 0.85) for the primary composite outcome (p < 0.05). At 3 h, the sensitivity/specificity for index-MI was ≥97%/≥82%, for 7-day MI was ≥89%/≥84%, and for the primary composite outcome was ≥90%/≥85% using the manufacturer's sex-specific 99th-percentile cutoffs. CONCLUSION: The Ortho hs-cTnI assay has superior analytical and clinical performance over their contemporary cTnI-ES assay in evaluating ED patients with symptoms suggestive of ACS.

Selective photothermal killing of cancer cells using LED-activated nucleus targeting fluorescent carbon dots.

The development of effective theranostic probes in cancer therapy is hampered due to issues with selectivity and off-target toxicity. We report the selective LED-photothermal ablation of cervical (HeLa) cancer cells over human dermal fibroblasts (HDF) using a new class of green-emissive fluorescent carbon dots (FCDs). The FCDs can be easily prepared in one pot using cheap and commercial starting materials. Physico-chemical characterization revealed that a surface coating of 2,5-deoxyfructosazine on a robust amorphous core gives rise to the nanomaterial's unique properties. We show that intracellular uptake mostly involves passive mechanisms in combination with intracellular DNA interactions to target the nucleus and that cancer cell selective killing is likely due to an increase in intracellular temperature in combination with ATP depletion, which is not observed upon exposure to either the "naked" core FCDs or the surface components individually. The selectivity of these nanoprobes and the lack of apparent production of toxic metabolic byproducts make these new nanomaterials promising agents in cancer therapy.

Evaluation of the Siemens ADVIA Centaur high-sensitivity cardiac troponin I assay in serum.

BACKGROUND: International recommendations on high-sensitivity cardiac troponin (hs-cTn) testing recommend that laboratories select only one sample type for testing. We evaluated the Siemens ADVIA Centaur hs-cTnI assay in serum and thereby provide information on imprecision, long-term storage stability, freeze-thaw stability, method comparison to other hs-cTnI assays, and clinical performance. METHODS: Patients with chest pain onset <6 h who already had Roche hs-cTnT, Beckman hs-cTnI and Abbott hs-cTnI results recorded and had non-thawed and frozen serum aliquots formed the study population (n = 134 patients with 305 serum aliquots obtained at either 0, 3 or 6 h stored below -70 °C since 2003) for measurement with the Siemens hs-cTnI assay in 2018. Receiver-operating characteristic curve analyses for myocardial infarction (MI) using the highest obtained hs-cTn concentration was performed. Additional comparison testing on serum samples stored frozen (at -70 °C for <1 month in 2018) for the Siemens and Abbott hs-cTnI assays were performed, as well as precision testing in serum pools and freeze-thaw stability testing. RESULTS: The Siemens hs-cTnI assay had an area under the curve (AUC) of 0.978 (95%CI: 0.937-0.996) for MI in the study cohort (Roche hs-cTnT AUC = 0.965 and Abbott AUC = 0.973). The Siemens hs-cTnI assay yielded higher cTnI concentrations than the other hs-cTn assays, with the same proportional bias (slope = 1.4) between the Siemens and Abbott hs-cTnI assays obtained from serum samples collected in 2003 and 2018. Over 3 months, a low serum pool of 3.5 ng/l achieved a CV of 20% (SD = 0.7, n = 42) and a high serum pool of 820 ng/l achieved a CV of 2.3% (SD = 20, n = 42). Three different serum pools recovered within 10% from baseline concentration after 5 freeze-thaw cycles for the Siemens hs-cTnI assay. CONCLUSIONS: In serum, the Siemens ADVIA Centaur hs-cTnI assay had excellent clinical performance for MI in an early chest pain onset population, acceptable precision at normal and highly elevated cTnI concentrations, long-term storage stability (15 y storage below -70 °C) and acceptable freeze-thaw stability, all of which supports serum as an acceptable sample type to use in clinical studies and in clinical practice.

Recent Developments in Solid-Phase Strategies towards Synthetic, Sequence-Defined Macromolecules.

Sequence-control in synthetic polymers is an important contemporary research area because it provides the opportunity to create completely novel materials for structure-function studies. This is especially relevant for biomimetic polymers, bioactive and information security materials. The level of control is strongly dependent and inherent upon the polymerization technique utilized. Today, the most established method yielding monodispersity and monomer sequence-definition is solid-phase synthesis. This Focus Review highlights recent advances in solid-phase strategies to access synthetic, sequence-defined macromolecules. Alternatives strategies towards sequence-defined macromolecules are also briefly summarized.

Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department.

BACKGROUND: Testing for high-sensitivity cardiac troponin (hs-cTn) may assist triage and clinical decision-making in patients presenting to the emergency department with symptoms of acute coronary syndrome; however, this could result in the misclassification of risk because of analytical variation or laboratory error. We sought to evaluate a new laboratory-based risk-stratification tool that incorporates tests for hs-cTn, glucose level and estimated glomerular filtration rate to identify patients at risk of myocardial infarction or death when presenting to the emergency department. METHODS: We constructed the clinical chemistry score (CCS) (range 0-5 points) and validated it as a predictor of 30-day myocardial infarction (MI) or death using data from 4 cohort studies involving patients who presented to the emergency department with symptoms suggestive of acute coronary syndrome. We calculated diagnostic parameters for the CCS score separately using high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: For the combined cohorts (n = 4245), 17.1% of participants had an MI or died within 30 days. A CCS score of 0 points best identified low-risk participants: the hs-cTnI CCS had a sensitivity of 100% (95% confidence interval [CI] 99.5%-100%), with 8.9% (95% CI 8.1%-9.8%) of the population classified as being at low risk of MI or death within 30 days; the hs-cTnT CCS had a sensitivity of 99.9% (95% CI 99.2%-100%), with 10.5% (95% CI 9.6%-11.4%) of the population classified as being at low risk. The CCS had better sensitivity than hs-cTn alone (hs-cTnI < 5 ng/L: 96.6%, 95% CI 95.0%-97.8%; hs-cTnT < 6 ng/L: 98.2%, 95% CI 97.0%-99.0%). A CCS score of 5 points best identified patients at high risk (hs-cTnI CCS: specificity 96.6%, 95% CI 96.0%-97.2%; 11.2% [95% CI 10.3%-12.2%] of the population classified as being at high risk; hs-cTnT CCS: specificity 94.0%, 95% CI 93.1%-94.7%; 13.1% [95% CI 12.1%-14.1%] of the population classified as being at high risk) compared with using the overall 99th percentiles for the hs-cTn assays (specificity of hs-cTnI 93.2%, 95% CI 92.3-94.0; specificity of hs-cTnT 73.8%, 95% CI 72.3-75.2). INTERPRETATION: The CCS score at the chosen cut-offs was more sensitive and specific than hs-cTn alone for risk stratification of patients presenting to the emergency department with suspected acute coronary syndrome. Study registration: ClinicalTrials.gov, nos. NCT01994577; NCT02355457.

Practical Three-Minute Synthesis of Acid-Coated Fluorescent Carbon Dots with Tuneable Core Structure.

We report a one-pot, three-minute synthesis of carboxylic acid-decorated fluorescent carbon dots (COOH-FCDs) with tuneable core morphology dependent on the surface passivating agent. Mechanism investigations highlighted the presence of key pyrazine and polyhydroxyl aromatic motifs, which are formed from the degradation of glucosamine in the presence of a bifunctional linker bearing acid and amine groups. The novel COOH-FCDs are selective Fe3+ and hemin sensors. Furthermore, the FCDs are shown to be non-toxic, fluorescent bioimaging agents for cancer cells.

Surface functionalisation significantly changes the physical and electronic properties of carbon nano-dots.

Biomolecule functionalisation of carbon nano-dots (CDs) greatly enhances their biocompatibility and applicability, however, little is known about their molecular structure. Using an arsenal of spectroscopic and analytical techniques, we provide new insights into the physical and electronic structure of uncoated and glycan-functionalised CDs. Our studies reveal that surface functionalisation does not always result in a homogenous corona surrounding the core, and the choice of carbohydrate significantly affects the electronic structure of the surface CD states. Further, the average surface coverage of an ensemble of CDs can be probed via transient absorption spectroscopy. These findings have implications for CDs targeted at interactions with biological systems or local sensors.

Performance of high-sensitivity cardiac troponin in the emergency department for myocardial infarction and a composite cardiac outcome across different estimated glomerular filtration rates.

BACKGROUND: Clinicians regularly observe increased high-sensitivity cardiac troponin (hs-cTn) concentrations in patients with low estimated glomerular filtration rate (eGFR). The challenge is to differentiate acute coronary syndrome (ACS) from increased hs-cTn results across a range of eGFR. The objective of this study was to determined the optimal hs-cTn concentrations for acute myocardial infarction (MI) and a composite cardiovascular outcome across different eGFR ranges and to assess the utility of a low hs-cTn cutoff to rule-out events. METHODS: We undertook an observational study in the emergency department of patients (n = 1212) with symptoms suggestive of ACS who had an eGFR and at least one Roche hs-cTnT and one Abbott hs-cTnI result. The 7-day outcomes were MI or a composite of MI, unstable angina, congestive heart failure, serious ventricular cardiac arrhythmia, or death. The maximum hs-cTn concentration was assessed across different eGFR ranges (<30,30-59,60-89,≥90 ml/min/1.73m2) by spearman correlation, ROC-curve analyses, and sensitivity and negative predictive value (NPV) for the proposed rule-out hs-cTn cutoffs (hs-cTnI<5 ng/l and hs-cTnT<6 ng/l) for the outcomes. RESULTS: Both hs-cTnI and hs-cTnT concentrations were negatively correlated with eGFR. The lower the eGFR, the lower the AUC and the higher the optimal hs-cTn cutoffs for both MI and the composite outcome. The highest combined sensitivity (100%), NPV (100%) and proportion of low-risk for MI (45% of group) was observed for patients with hs-cTnT<6 ng/l with an eGFR≥90. CONCLUSION: The test performance for hs-cTn for diagnosing or ruling-out an acute cardiac event varies per the eGFR. Accurate risk stratification requires knowledge of the eGFR.

High-sensitivity cardiac troponin concentrations at emergency department presentation in females and males with an acute cardiac outcome.

Background There is interest in utilizing different cut-offs per sex for high-sensitivity cardiac troponin I (hs-cTnI) but less so for high-sensitivity cardiac troponin T (hs-cTnT) for patient management in the acute setting. Our objective was to assess if differences in hs-cTn concentrations exist between males and females for an acute cardiac outcome following the presentation measurement in the emergency department. Methods An observational emergency department population with hs-cTn measurements (Roche Diagnostics and Abbott Diagnostics) at presentation with seven-day outcomes for a composite acute cardiac outcome (i.e. myocardial infarction, unstable angina, ventricular arrhythmia, heart failure or cardiovascular death) (ClinicalTrials.gov: NCT01994577). Receiver operating characteristic curve analyses were performed for each sex with both hs-cTn assays. Results In those patients who had a composite acute cardiac outcome ( n = 128 females; n = 145 males), there was no difference in hs-cTn concentrations between the sexes (median [IQR] female hs-cTnT = 35 ng/L [21-69] vs. male hs-cTnT = 38 ng/L [19-77], P = 0.95; and median [IQR] female hs-cTnI = 27 ng/L [12-75] vs. male hs-cTnI = 26 ng/L [12-85], P = 0.97]. There was also no difference in the area under the curve between the hs-cTn assays and between the sexes ( P > 0.10). Comparing hs-cTn concentrations in those patients with the composite outcome between the sexes <60 years and ≥60 years of age also did not yield significant differences ( P > 0.70). Conclusions The concentrations and area under the curves of hs-cTnT and hs-cTnI at patient presentation in the emergency department for an acute composite cardiac outcome were similar between the sexes in this exploratory study.

Analytical comparison of three different versions of a high-sensitivity cardiac troponin I assay over 10years.

BACKGROUND: Concerns have been raised on the long-term analytical performance of high-sensitivity cardiac troponin (hs-cTn) assays with respect to different reagent formulations, lots and instrumentation. Our goal for the present study was to compare three different versions of an hs-cTnI assay in two different study populations to evaluate if assay re-formulation over 10years has also affected the analytical results. METHODS: Beckman Coulter's CE marked hs-cTnI assay (Access hsTnI, 2017) was tested in 100 lithium heparin plasma samples first tested in 2007 with their prototype hs-cTnI assay and in 100 serum samples tested with their enhanced hs-cTnI assay in 2011 with comparison performed by Passing-Bablok regression. The Beckman Coulter hs-cTnI results from 2017 and 2011 from the serum samples were also compared to the Abbott ARCHITECT i1000 hs-cTnI results (2013) with 3-fold differences used to identify possible outliers. Freeze/thaw stability testing (-20°C) was also performed on normal cTnI (Beckman=4.0ng/L; Abbott=5.3ng/L) and high cTnI concentration (Beckman=77.6ng/L; Abbott=126.1ng/L) lithium heparin plasma pools for both hs-cTnI assays. RESULTS: After 3 freeze-thaws the Beckman hs-cTnI assay yielded minor decreases in concentrations (normal pool -0.7ng/L and high pool -12.6ng/L lower). Regression analyses yielded the following relationship between the Beckman hs-cTnI versions: 2017 hs-cTnI=2.0*(2007 prototype hs-cTnI)-5.1ng/L and 2017 hs-cTnI=1.04∗(2011 enhanced hs-cTnI)-2.5ng/L. Compared to the Abbott 2013 hs-cTnI results, the 2011 Beckman enhanced version had 8 results 3-fold higher, with the 2017 Beckman version yielding 6 results 3-fold lower. CONCLUSIONS: The 2017 Beckman hs-cTnI version (Access hsTnI) is closely aligned with the previous enhanced hs-cTnI assay and appears to have reduced the frequency of aberrantly high results.

High-Sensitivity Cardiac Troponin Risk Cutoffs for Acute Cardiac Outcomes at Emergency Department Presentation.

The optimal high-sensitivity cardiac troponin (hs-cTn) cutoffs for determining risk in patients who present with acute coronary syndrome symptoms are unknown. In 1137 emergency department patients we calculated adjusted relative risks for a composite outcome (myocardial infarction, unstable angina, heart failure, ventricular arrhythmia, or cardiovascular death) within 7 days for the presentation of hs-cTnT (Roche) and hs-cTnI (Abbott) assay concentrations on the basis of literature cutoffs. Patients with hs-cTn concentrations ≥ 14 ng/L had an adjusted relative risk of 4.9 for the composite outcome, with different hs-cTnT/hs-cTnI concentration ranges yielding higher risks. A common low-risk cutoff of 14 ng/L may be used for hs-cTn with higher cutoffs identifying high-risk patients.

A laboratory score at presentation to rule-out serious cardiac outcomes or death in patients presenting with symptoms suggestive of acute coronary syndrome.

BACKGROUND: We evaluated whether a low high-sensitivity cardiac troponin (hs-cTn) cutoff combined with glucose, red cell distribution width (RDW), and the estimated glomerular filtration rate (eGFR) can be used to rule-out a serious cardiac outcome or death in patients presenting with symptoms suggestive of acute coronary syndrome (ACS). METHODS: This was a prospective observational emergency department (ED) study enrolling consecutive patients presenting with symptoms suggestive of ACS (ClinicalTrials.gov: NCT01994577). The primary outcome was a 7-day composite of myocardial infarction, unstable angina, decompensated congestive heart failure, serious ventricular cardiac arrhythmia, or death. A laboratory score combining glucose, RDW, eGFR with hs-cTnT (Roche) or hs-cTnI (Abbott) was compared to hs-cTn alone using the limit of detection (LoD; hs-cTnT<5ng/l/hs-cTnI<2ng/l) as the cutoff. A benchmark of >99% sensitivity was used to assess the laboratory panel with hs-cTn versus the LoD alone to identify low-risk patients suitable for discharge. RESULTS: A total of 1095 patients (n=267 composite-outcomes) had measurements of glucose, RDW, eGFR, hs-cTnT, and hs-cTnI at presentation. Applying the hs-cTn LoD alone as the cutoff missed 5 composite-outcomes (sensitivity=98.1%), however the addition of the laboratory panel to the hs-cTn LoD increased the sensitivity to >99% with approximately 10% of the population identified as low-risk. The percentage of low-risk patients was increased to 15% (1 composite-outcome missed) when employing a low measurable hs-cTnI cutoff with the laboratory panel (laboratory score<2 points). CONCLUSION: A laboratory score with hs-cTn may identify low-risk patients suitable for ED discharge at presentation.

Rule-In and Rule-Out of Myocardial Infarction Using Cardiac Troponin and Glycemic Biomarkers in Patients with Symptoms Suggestive of Acute Coronary Syndrome.

BACKGROUND: Early rule-in/rule-out of myocardial infarction (MI) in patients presenting to the emergency department (ED) is important for patient care and resource allocation. Given that dysglycemia is a strong risk factor for MI, we sought to explore and compare different combinations of cardiac troponin (cTn) cutoffs with glycemic markers for the early rule-in/rule-out of MI. METHODS: We included ED patients (n = 1137) with symptoms suggestive of acute coronary syndrome (ACS) who had cTnI, high-sensitivity cTnI (hs-cTnI), hs-cTnT, glucose, and hemoglobin A1c (Hb A1c) measurements. We derived rule-in/rule-out algorithms using different combinations of ROC-derived and literature cutoffs for rule-in and rule-out of MI within 7 days after presentation. These algorithms were then tested for MI/cardiovascular death and ACS/cardiovascular death at 7 days. ROC curves, sensitivity, specificity, likelihood ratios, positive and negative predictive values (PPV and NPV), and CIs were determined for various biomarker combinations. RESULTS: MI was diagnosed in 133 patients (11.7%; 95% CI, 9.8-13.8). The algorithms that included cTn and glucose produced the greatest number of patients ruled out/ruled in for MI and yielded sensitivity ≥99%, NPV ≥99.5%, specificity ≥99%, and PPV ≥80%. This diagnostic performance was maintained for MI/cardiovascular death but not for ACS/cardiovascular death. The addition of hemoglobin A1c (Hb A1c) (≥6.5%) to these algorithms did not change these estimates; however, 50 patients with previously unknown diabetes may have been identified if Hb A1c was measured. CONCLUSIONS: Algorithms incorporating glucose with cTn may lead to an earlier MI diagnosis and rule-out for MI/cardiovascular death. Addition of Hb A1c into these algorithms allows for identification of diabetes. Future studies extending these findings are needed for ACS/cardiovascular death. ClinicalTrials.gov identifier: NCT01994577.

Economic Considerations of Early Rule-In/Rule-Out Algorithms for The Diagnosis of Myocardial Infarction in The Emergency Department Using Cardiac Troponin and Glycemic Biomarkers.

BACKGROUND: We have previously demonstrated the utility of a rule-in/rule-out strategy for myocardial infarction (MI) using glycemic biomarkers in combination with cardiac troponin in the emergency department (ED). Given that the cost of assessing patients with possible MI in the ED is increasing, we sought to compare the health services cost of our previously identified early rule-in/rule-out approaches for MI among patients who present to the ED with symptoms suggestive of acute coronary syndrome (ACS). METHODS: We compared the cost differences between different rule-in/rule-out strategies for MI using presentation cardiac troponin I (cTnI), high-sensitivity cTnI (hs-cTnI), high-sensitivity cardiac troponin T (hs-cTnT), glucose, and/or hemoglobin A1c (Hb A1c) in 1137 ED patients (7-day MI n = 133) as per our previously defined algorithms and compared them with the European Society of Cardiology (ESC) 0-h algorithm-cutoffs. Costs associated with each decision model were obtained from site-specific sources (length of stay) and provincial sources (Ontario Case Costing Initiative). RESULTS: Algorithms incorporating cardiac troponin and glucose for early rule-in/rule-out were the most cost effective and clinically safest methods (i.e., ≤1 MI missed) for early decision making, with hs-cTnI and glucose yielding lower costs compared to cTnI and glucose, despite the higher price for the hs-cTnI test. The addition of Hb A1c to the algorithms increased the cost of these algorithms but did not miss any additional patients with MI. Applying the ESC 0-h algorithm-cutoffs for hs-cTnI and hs-cTnT were the most costly. CONCLUSIONS: Rule-in/rule-out algorithms incorporating presentation glucose with high-sensitivity cardiac troponin are the safest and most cost-effective options as compared to the ESC 0-h algorithm-cutoffs.

Three-minute synthesis of sp3 nanocrystalline carbon dots as non-toxic fluorescent platforms for intracellular delivery.

A one-pot, three-minute, gram-scale synthesis of novel sp3-nanocrystalline, water-soluble, and fluorescent carbon dots (FCDs), from simple and cheap sugar starting materials is described. Mechanism studies showed that NH2-FCD formation proceeds via a crucial imine intermediate derived from reaction between a sugar hemiacetal and an amine. Moreover, we successfully demonstrate the utility of lactose functionalized FCDots (Lac-FCDots) as non-toxic fluorescent intracellular delivery vehicles.