Pre-hospital rule-out of non-ST-segment elevation acute coronary syndrome by a single troponin: final one-year outcomes of the ARTICA randomised trial.

BACKGROUND AND AIMS: The healthcare burden of acute chest pain is enormous. In the randomised ARTICA trial we showed that pre-hospital identification of low-risk patients and rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with point-of-care (POC) troponin measurement reduces 30-day healthcare costs with low major adverse cardiac events (MACE) incidence. Here we present the final one-year results of the ARTICA trial. METHODS: Low-risk patients with suspected NSTE-ACS were randomised to pre-hospital rule-out with POC troponin measurement or emergency department (ED) transfer. Primary one-year outcome was healthcare costs. Secondary outcomes were safety, quality of life (QoL) and cost-effectiveness. Safety was defined as one-year MACE, consisting of ACS, unplanned revascularisation or all-cause death. QoL was measured with EuroQol-5D-5 L questionnaires. Cost-effectiveness was defined as one-year healthcare costs difference per QoL difference. RESULTS: Follow-up was completed in all 863 patients. Healthcare costs were significantly lower in the pre-hospital strategy (€1932±€2784 vs €2649±€2750), mean difference €717 (95% confidence interval [CI] €347 to €1087; P < 0.001). In the total population, one-year MACE rate was comparable between groups (5.1% [22/434] in the pre-hospital strategy vs 4.2% [18/429] in the ED strategy; P = 0.54). In the ruled-out ACS population, one-year MACE remained low (1.7% [7/419] vs 1.4% [6/417]), risk difference 0.2% (95% CI -1.4% to 1.9%; P = 0.79). QoL showed no significant difference between strategies. CONCLUSIONS: Pre-hospital rule-out of NSTE-ACS with POC troponin testing in low-risk patients is cost-effective, expressed by a sustainable healthcare costs reduction and no significant effect on QoL. One-year MACE remained low for both strategies. Trial registration: Clinicaltrials.gov: NCT05466591, International Clinical Trials Registry Platform: NTR7346.

Efficiency of ultrafiltration/diafiltration in removing organic and elemental process equipment related leachables from biological therapeutics.

In the production of biological therapeutics such as monoclonal antibodies (mAbs), ultrafiltration and diafiltration (UF/DF) are widely regarded as effective downstream processing steps capable of removing process equipment related leachables (PERLs) introduced upstream of the UF/DF step. However, clearance data available in the literature are limited to species with low partition coefficients (log P) such as buffer ions, hydrophilic organic compounds, and some metal ions. Additional data for a wide range of PERLs including hydrophobic compounds and elemental impurities are needed to establish meaningful, comprehensive safety risk assessments. Herein, we report the results from studies investigating the clearance of seven different organic PERLs representing a wide range of characteristics (i.e., log P (-0.3 to 18)), and four model elements with different chemical properties spiked into a mAb formulation at 10 ppm and analyzed during clearance using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-photodiode-array-mass spectrometry (LC-PDA-MS), and inductively coupled plasma mass spectrometry (ICP-MS). The clearance data showed ideal clearance and sieving of spiked organic PERLs with log P < 4, partial clearance of PERLs with 4 < log P < 9, and poor clearance of highly hydrophobic PERLs (log P > 9) after nine diafiltration volumes (DVs). Supplemental clearance studies on seven additional PERLs present at much lower concentration levels (0.1-1.5 ppm) in the mAb formulation upstream of UF/DF and three PERLs associated with the tangential flow filtration (TFF) equipment also demonstrated the similar correlations between log P and % clearance. For model elements, the findings suggest that UF/DF in general provides ideal clearance for elements. Evidence showed that the UF/DF process does not only help mitigate leachables risk from PERLs introduced upstream of UF/DF, but also from the TFF operation itself as all three TFF-related PERLs were effectively cleared. Overall, the UF/DF clearance presented in this work demonstrated whereas highly hydrophobic PERLs and elements that exist as charged species, particularly transition metal ions, may not be as effectively cleared and thus warrant further risk assessment; hydrophilic and some hydrophobic PERLs (log P < 4) are indeed well-cleared and thus present a lower overall safety risk.

Differences in risk and costs between prehospital identified low-risk men and women with chest pain.

OBJECTIVE: Prehospital rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in low-risk patient with a point-of-care troponin measurement reduces healthcare costs with similar safety to standard transfer to the hospital. Risk stratification is performed identical for men and women, despite important differences in clinical presentation, risk factors and age between men and women with NSTE-ACS. Our aim was to compare safety and healthcare costs between men and women in prehospital identified low-risk patients with suspected NSTE-ACS. METHODS: In the Acute Rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART (History, ECG, Age, Risk factors and Troponin) score assessment and a single poInt of CAre troponin randomised trial, the HEAR (History, ECG, Age and Risk factors) score was assessed by ambulance paramedics in suspected NSTE-ACS patients. Low-risk patients (HEAR score ≤3) were included. In this substudy, men and women were compared. Primary endpoint was 30-day major adverse cardiac events (MACE), secondary endpoints were 30-day healthcare costs and the scores for the HEAR score components. RESULTS: A total of 863 patients were included, of which 495 (57.4%) were women. Follow-up was completed in all patients. In the total population, MACE occurred in 6.8% of the men and 1.6% of the women (risk ratio (RR) 4.2 (95% CI 1.9 to 9.2, p<0.001)). In patients with ruled-out ACS (97% of the total population), MACE occurred in 1.4% of the men and in 0.2% of the women (RR 7.0 (95% CI 2.0 to 14.2, p<0.001). Mean healthcare costs were €504.55 (95% CI €242.22 to €766.87, p<0.001) higher in men, mainly related to MACE. CONCLUSIONS: In a prehospital population of low-risk suspected NSTE-ACS patients, 30-day incidence of MACE and MACE-related healthcare costs were significantly higher in men than in women. TRIAL REGISTRATION NUMBER: NCT05466591.

Management of encounters related to subfertility and infertility in Australian general practice: a focus on Aboriginal and Torres Strait Islander females.

OBJECTIVE: To investigate the management of subfertility and infertility among Aboriginal and Torres Strait Islander females attending Australian general practice. METHODS: Cross-sectional study of 1,258,581 women (18-49 years) attending general practice between January 2011 and June 2019, utilising data from NPS MedicineWise MedicineInsight, a national general practice database in Australia. RESULTS: The prevalence of subfertility/infertility encounters was lower for Aboriginal and Torres Strait Islander females (12.37 per 1,000) than for non-Indigenous females (16.62 per 1,000). Aboriginal and Torres Strait Islander females with a subfertility/infertility encounter were younger and more likely to live outside Major cities and in areas of socioeconomic disadvantage than non-Indigenous females. Rates of prescribed infertility medications were not different between groups, however Aboriginal and Torres Strait Islander females were more likely to receive a pelvic ultrasound (24.30% vs. 19.90%); tests for luteinizing hormone (31.89% vs. 25.65%); testosterone (14.93% vs. 9.96%) and; glycated haemoglobin (HbA1c) (6.32% vs. 3.41%),but less likely to receive an anti-müllerian hormone test (2.78% vs. 7.04%). CONCLUSIONS: Lower encounter rates for infertility/subfertility among Aboriginal and Torres Strait Islander peoples may indicate access issues, preferred use of Aboriginal community-controlled health centres or younger average age at first birth and thus less age-related infertility. IMPLICATIONS FOR PUBLIC HEALTH: Future efforts should focus on maximising the inclusiveness of infertility surveillance. There is also a need for further research into the experiences of and preferences for infertility care and associated barriers among Aboriginal and Torres Strait Islander people.

Rule-out of non-ST-segment elevation acute coronary syndrome by a single, pre-hospital troponin measurement: a randomized trial.

AIMS: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are routinely transferred to the emergency department (ED). A clinical risk score with point-of-care (POC) troponin measurement might enable ambulance paramedics to identify low-risk patients in whom ED evaluation is unnecessary. The aim was to assess safety and healthcare costs of a pre-hospital rule-out strategy using a POC troponin measurement in low-risk suspected NSTE-ACS patients. METHODS AND RESULTS: This investigator-initiated, randomized clinical trial was conducted in five ambulance regions in the Netherlands. Suspected NSTE-ACS patients with HEAR (History, ECG, Age, Risk factors) score ≤3 were randomized to pre-hospital rule-out with POC troponin measurement or direct transfer to the ED. The sample size calculation was based on the primary outcome of 30-day healthcare costs. Secondary outcome was safety, defined as 30-day major adverse cardiac events (MACE), consisting of ACS, unplanned revascularization or all-cause death. : A total of 863 participants were randomized. Healthcare costs were significantly lower in the pre-hospital strategy (€1349 ± €2051 vs. €1960 ± €1808) with a mean difference of €611 [95% confidence interval (CI): 353-869; P < 0.001]. In the total population, MACE were comparable between groups [3.9% (17/434) in pre-hospital strategy vs. 3.7% (16/429) in ED strategy; P = 0.89]. In the ruled-out ACS population, MACE were very low [0.5% (2/419) vs. 1.0% (4/417)], with a risk difference of -0.5% (95% CI -1.6%-0.7%; P = 0.41) in favour of the pre-hospital strategy. CONCLUSION: Pre-hospital rule-out of ACS with a POC troponin measurement in low-risk patients significantly reduces healthcare costs while incidence of MACE was low in both strategies. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT05466591 and International Clinical Trials Registry Platform id NTR 7346.

"You get past the packaging": young women smokers' resistance to standardized cigarette packaging.

We examined how young women construct and experience plain tobacco packaging. Forty-one Australian young women who are current smokers took part in this qualitative interview research. Data was analyzed using constructivist grounded theory, with the core category about the strategic ways young women resist plain tobacco packaging. The majority of women reported that plain packaging was unappealing and that the larger health warnings were shocking and offensive. However, almost all reported being desensitized to the graphic health warnings. The graphic warnings were seen as "fake" or lacking in credibility, and irrelevant to the women's life stage. Importantly, the majority of women engaged in practices to strategically resist and avoid health warnings on the packs as a way to continue smoking. Our findings point to the need to develop health warnings on tobacco products that are gender specific and focus on proximal social consequences to increase salience for young women smokers.

Incidence of Respiratory Pathogens in Naval Special Warfare Sea, Air, and Land Team Candidates With Swimming-Induced Pulmonary Edema.

BACKGROUND: Swimming-induced pulmonary edema (SIPE) is a respiratory condition frequently seen among Naval Special Warfare (NSW) trainees. The incidence of positive respiratory panel (RP) findings in trainees with a diagnosis of SIPE currently is unknown. RESEARCH QUESTION: Does a significant difference exist in the incidence of respiratory pathogens in nasopharyngeal samples of NSW candidates with SIPE and a control group? STUDY DESIGN AND METHODS: Retrospective analysis of clinical information from NSW Sea, Air, and Land (SEAL) team candidates with a diagnosis of SIPE over a 12-month period. Candidates who demonstrated the common signs and symptoms of SIPE underwent a nasopharyngeal swab and RP test for common respiratory pathogens. SIPE diagnoses were supported by two-view chest radiography. RP tests were obtained for a selected control group of first-phase trainees without SIPE. RESULTS: Forty-five of 1,048 SEAL team candidates received a diagnosis of SIPE (4.3%). Five had superimposed pneumonia. Thirty-six of 45 showed positive results for at least one microorganism on the RP (80%). In the study group, human rhinovirus/enterovirus (RV/EV) was the most frequently detected organism (37.8%), followed by coronavirus OC43 (17.8%), and parainfluenza virus type 3 (17.8%). Sixteen of 68 candidates from the control group showed positive RP (24%) findings. Patients with SIPE and positive RP results reported dyspnea (94%), pink frothy sputum (44%), and hemoptysis (36%) more frequently than the control participants with positive RP results. Those who reported respiratory infection symptoms in both the study and control groups showed higher incidences of positive RP results (P = .046). INTERPRETATION: We observed that 80% of trainees with a diagnosis of SIPE showed positive results on a point-of-care RP. This positivity rate was significantly higher than that of RP test results from the control cohort. These findings suggest an association between colonization with a respiratory pathogen and the development of SIPE in NSW candidates.

Dual-Energy, Dual-Exposure PA and Lateral Chest Radiograph: Not Your Father's Chest X-Ray.

In the last two decades, our military and federal health care facilities have transitioned from traditional X-rays exposing film screen systems, developed much like photographic film, to an entirely digital detection system that affords computer processing of images and digital image and report distribution. While health care providers are well aware of the practicality of these advancements, they may not be aware of the improved diagnostic capabilities afforded by these new methods. In this report, we outline how application of physical principles of X-rays, with digital detectors and computer data manipulation, can present images demonstrating chest and heart diseases that were previously not readily visible by traditional film screen systems. More recently, dual-energy, dual-exposure systems have been implemented. This commentary is to educate the medical community so that they may better understand not only the written report but the information on the images being provided, along with potential pitfalls to avoid. Specifically, we demonstrate improved detection of pulmonary nodules and coronary atherosclerosis with the dual-energy technique.

Epigenetic modifiers identified as regulators of food intake in a unique hypophagic chicken model.

DNA methylation is an epigenetic modification that influences gene transcription; however, the effects of methylation-influencing chemicals on appetite are unknown. We evaluated the effects of single administration of a methyl donor, S-Adenosylmethionine (SAM), or methylation inhibitor, 5-Azacytidine (AZA), on immediate and later-age food intake in an anorexic chick model. The doses of intracerebroventricularly-injected SAM were 0 (vehicle), 0.1, 1, and 10 µg, and of AZA were 0 (vehicle), 1, 5, and 25 µg. When injected on day 5 posthatch, there was no effect of SAM on food intake in either fed or fasted chicks, whereas AZA increased food consumption in the fasted state but decreased it in fed chicks. We then performed a single injection (same doses) at hatch and measured food intake on day 5 in response to neuropeptide Y (NPY; 0.2 µg) injection. Irrespective of NPY, chicks injected with 1 µg of SAM ate more than others on day 5. In contrast, chicks injected with AZA (5 and 25 µg doses) consumed less on day 5. In conclusion, we identified DNA methylation-regulating chemicals as regulators of food intake. AZA but not SAM affected food intake in the short-term, feeding state dependently. Later, both chemicals injected on the day of hatch were associated with food intake changes at a later age, suggesting that feeding pathways might be altered through changes in methylation.

Opportunistic Detection of Coronary Calcium on Dual-Energy Lateral Chest Radiograph.

ABSTRACT: Heart disease remains the leading cause of death among men and women in the world. The majority of cardiac morbidity worldwide is secondary to atherosclerotic coronary disease. In this article, we discuss our experience using dual exposure, dual-energy lateral chest x-ray (CXR) technique to detect coronary calcium. Similar to other reports demonstrating opportunistic detection on imaging studies, here we demonstrate the added value of detection of coronary calcium on the lateral CXR. This technique reinforces the importance of "knowing where to look" and to recognize the appearance of coronary calcium wherein subtle cardiac motion can be a useful artifact in the accurate detection of coronary calcium. In addition, we discuss correlating coronary calcium burden with age, elaborate on the physics behind coronary calcium detection, and how best to optimize imaging technique. Lastly, we show other uses of dual-energy lateral CXR technique to illustrate where using material decomposition and subtle motion can better define contours in the mediastinum and lung.

Implementation of the ESC 0 h/1h algorithm and the HEART score in the emergency department: A prospective cohort study.

Background: The European Society of Cardiology (ESC) 0 h/1h algorithm is the preferred diagnostic strategy for chest pain patients in the emergency department (ED). It is suggested that adding clinical information to the algorithm improves its diagnostic performance. This study evaluates implementation of the ESC 0 h/1h algorithm in the ED and investigates the potential advantages of combining it with a clinical decision rule, which might be especially relevant in the heterogenous observation category. Methods: In this prospective cohort study, chest pain patients in whom the ESC 0 h/1h algorithm was applied were enrolled. HEART score components were collected. Diagnostic characteristics were determined for the algorithm with and without addition of the HEART score. Primary endpoint was a composite endpoint at 30-day follow-up, consisting of myocardial infarction and death. Results: A total of 668 patients were enrolled. The rule-in and rule-out categories consisted of 8.2% and 54.9% of the patients, respectively. Positive predictive value and specificity of the rule-in category were 67.3% and 97.1%, respectively. Negative predictive value (NPV) and sensitivity of the rule-out category were both 100%. In the observation category, a HEART score ≤ 3 yielded a NPV and sensitivity of 97.1% and 93.8%, respectively. Conclusion: The ESC 0 h/1h algorithm yielded a NPV and sensitivity of 100% for myocardial infarction and death at 30-day follow-up. Addition of the HEART score did not provide clinically relevant advantages. Although the HEART score can be used to guide diagnostic testing in the observation category, a low HEART score did not yield an NPV of > 99%.

Multimodality Imaging Assessment of Anomalous Aortic Origin of the Left Main Coronary Artery Presenting With Syncope and Non-ST Elevation Myocardial Infarction.

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital abnormality associated with myocardial ischemia and sudden cardiac death. We present a case of a 20 year old previously healthy male presenting with exertional syncope and non-ST elevation myocardial infarction. Coronary computed tomography angiography showed an anomalous left main coronary artery arising from the right coronary cusp with a slit-like appearance, acute angle origin, intramural course, and a subsequent inter-arterial course between the main pulmonary artery and the proximal aorta. Cardiac magnetic resonance imaging demonstrated myocardial infarction in the distribution of the left main coronary artery. The patient underwent successful surgical correction with unroofing of the left main coronary artery. He has had no syncopal episodes or recurrence of chest pain and returned to full duty status in the United States Marine Corps. This case report demonstrates the evaluation and management of a patient with AAOCA.

Prevalence and determinants of use of traditional methods of infertility treatment among women attending infertility clinic in Southeast Nigeria.

Infertility, an obstacle to healthy living, makes its victims patronize traditional methods of infertility treatment (TMIT) in spite of associated complications. They turn to hospitals when this method fails. This is actually a serious issue because the presence of contaminated herbal products and the relationship between the use of TMIT and noncompliance with biomedical treatment regimens constitutes a major concern in medical practice. And the use of traditional methods of infertility treatment has been correlated with severe and fatal consequences. Therefore, the study assessed prevalence/determinants of TMIT use among patients visiting the gynaecology clinic at Alex Ekwueme Federal University Teaching Hospital Abakaliki (AE-FUTHA). Descriptive cross-sectional design was adopted for the research. Only 263 women took part in the study. The research instrument was questionnaire. Data were analyzed using descriptive statistics. Findings revealed that 95.4% of these women have used traditional methods for infertility treatment and factors influencing infertile women's use of TMIT are demographic characteristics, infertility duration, husbands' relatives' pressure and cheap cost of traditional medical treatment. Again, inability of infertile women to disclose TMIT use to healthcare providers makes effective treatment difficult. Therefore, these impediments expose infertile women to use TMIT. The result is a guide to healthcare providers who are expected to know the extent of their parents' use of TMIT.

Fresher with flavour: young women smokers' constructions and experiences of menthol capsule cigarettes and regular cigarettes.

BACKGROUND: Flavour capsule cigarettes are one of the fastest growing segments of the tobacco market, and there is evidence that Australian young people are increasingly using menthol flavoured capsule cigarettes. This qualitative research examines how young women construct and experience menthol flavour capsule cigarettes as part of their smoking practices, and explores the perceived differences between menthol capsule cigarettes and regular cigarettes. Semi-structured face-to-face in-depth interviews were conducted with 41 Australian young women smokers, using a constructivist grounded theory approach. RESULTS: Findings reveal that the perceived fresh and improved taste of menthol and the ability to customise the smoking process positively contributed to young women's experiences of smoking menthol capsule cigarettes. In particular, menthol capsule flavour cigarettes were constructed by the young women as "fresh", "light" and "minty", and "popping" the menthol capsule allowed the young women to personalise their smoking experience. CONCLUSION: These results indicate that specific public health campaigns and legislation should be developed to counter the powerfully alluring effects and the innovative appeal of menthol capsule cigarettes.

Transcription initiation as a control point in plastid gene expression.

The extensive processing and protein-assisted stabilization of transcripts have been taken as evidence for a viewpoint that the control of gene expression had shifted entirely in evolution from transcriptional in the bacterial endosymbiont to posttranscriptional in the plastid. This suggestion is however at odds with many observations on plastid gene transcription. Chloroplasts of flowering plants and mosses contain two or more RNA polymerases with distinct promoter preference and division of labor for the coordinated synthesis of plastid RNAs. Plant and algal plastids further possess multiple nonredundant sigma factors that function as transcription initiation factors. The controlled accumulation of plastid sigma factors and modification of their activity by sigma-binding proteins and phosphorylation constitute additional transcriptional regulatory strategies. Plant and algal plastids also contain dedicated one- or two-component transcriptional regulators. Transcription initiation thus continues to form a critical control point at which varied developmental and environmental signals intersect with plastid gene expression.

Effect of Triple Therapy with Budesonide-Formoterol-Tiotropium Versus Placebo-Tiotropium on Sleep Quality in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Factors responsible for poor sleep quality in patients with chronic obstructive pulmonary disease (COPD) includes the effects of medications. This study evaluates the effect of the inhaled triple therapy of budesonide-formoterol-tiotropium versus placebo-tiotropium on sleep quality in COPD patients. METHODS: Twenty-three patients (11 [48%] males; age 55 [51-60, 48--5] years; body mass index [BMI] 25 [22-30, 18-40] kg/m2; forced expiratory volume in 1 second [FEV1]1.10 [0.80 -1.90, 0.60-2.80] L, 42 [31-62, 24-75] % predicted) were studied. Ten patients were randomized to budesonide-formoterol-tiotropium and 13 patients to placebo-tiotropium. At baseline and after 28 days, patients completed spirometry, polysomnography, an Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), COPD-specific St George's Respiratory Questionnaire (SGRQ-C) and short form 36 (SF 36). RESULTS: After 28 days, there was a significant 29% increase in the bedtime FEV1 in the budesonide-formoterol-tiotropium group (from 0.75 [0.55-1.30, 0.50-2.40] L to 1.00 [0.75-1.55, 0.50-3.00] L, p=0.031), with no change in the placebo-tiotropium group (from 1.20 [0.80-1.50, 0.60-1.90] L to 1.15 [0.75-1.55, 0.50-1.80] L, p=0.91). No significant change was found post treatment in sleep efficiency or total sleep time in both the budesonide-formoterol-tiotropium group (from 78 [72-92, 62-98]% to 88 [77-92, 40-98]%, p=0.70 and 290 [268-358, 252-382] min to 342 [303-358, 157-372] min, p=0.77, respectively) and the placebo-tiotropium group (from 82 [75-88, 46-93]% to 84 [77-87, 62-94]%, p=0.96 and 320 [292-350, 180-378] min to 339 [303-349, 241-366] min, p=0.79, respectively). While there was no significant change in the arousal index in the budesonide-formoterol-tiotropium group (9 [5-16, 0-48] arousals/hour to 14 [9-17, 2-36] arousals/hour, p=0.43), a significant increase was seen in the placebo-tiotropium group (11 [4-13, 3--2] arousals/hour to 17 [11-21, 2-33] arousals/hour, p=0.027). Similarly, there was no change in the ESS in the budesonide-formoterol-tiotropium group (6 [3-8, 0-11] to 6 [5-8, 0-1]), p=0.44), but a marginally significant increase in the placebo-tiotropium group (8 [5-12, 2-18] to 10 [7-13, 5-18], p=0.07), with a significant difference in the ESS 28 days post treatment between the 2 groups (6 [5-8, 0-11] versus 10 [7-13, 5-18], p=0.043). There was no significant change in nocturnal oxygenation, sleep architecture, PSQI, SGRQ-C, or SF 36 in both groups. CONCLUSION: In patients with COPD, inhaled triple therapy with budesonide-formoterol-tiotropium as compared to placebo-tiotropium improves pulmonary function while preserving sleep quality and architecture.

Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury.

BACKGROUND: Troponin composition characterization has been implicated as a next step to differentiate among non-ST elevation myocardial infarction (NSTEMI) patients and improve distinction from other conditions with troponin release. We therefore studied coronary and peripheral troponin compositions in relation to clinical variables of NSTEMI patients. METHODS: Samples were obtained from the great cardiac vein (GCV), coronary sinus (CS), and peripheral circulation of 45 patients with NSTEMI. We measured total cTnI concentrations, and assessed both complex cTnI (binary cTnIC + all ternary cTnTIC forms), and large-size cTnTIC (full-size and partially truncated cTnTIC). Troponin compositions were studied in relation to culprit vessel localization (left anterior descending artery [LAD] or non-LAD), ischemic time window, and peak CK-MB value. RESULTS: Sampling occurred at a median of 25 hours after symptom onset. Of total peripheral cTnI, a median of 87[78-100]% consisted of complex cTnI; and 9[6-15]% was large-size cTnTIC. All concentrations (total, complex cTnI, and large-size cTnTIC) were significantly higher in the CS than in peripheral samples (P < 0.001). For LAD culprit patients, GCV concentrations were all significantly higher; in non-LAD culprit patients, CS concentrations were higher. Proportionally, more large-size cTnTIC was present in the earliest sampled patients and in those with the highest CK-MB peaks. CONCLUSIONS: In coronary veins draining the infarct area, concentrations of both full-size and degraded troponin were higher than in the peripheral circulation. This finding, and the observed associations of troponin composition with the ischemic time window and the extent of sustained injury may contribute to future characterization of different disease states among NSTEMI patients.

Regulation of Phaeodactylum plastid gene transcription by redox, light, and circadian signals.

Diatoms are a diverse group of photosynthetic unicellular algae with a plastid of red-algal origin. As prolific primary producers in the ocean, diatoms fix as much carbon as all rainforests combined. The molecular mechanisms that contribute to the high photosynthetic productivity and ecological success of diatoms are however not yet fully understood. Using the model diatom Phaeodactylum tricornutum, here we show rhythmic transcript accumulation of plastid psaA, psbA, petB, and atpB genes as driven by a free running circadian clock. Treatment with the electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea overrides the circadian signal by markedly downregulating transcription of psaA, petB, and atpB genes but not the psbA gene. Changes in light quantity produce little change in plastid gene transcription while the effect of light quality seems modest with only the psaA gene responding in a pattern that is dependent on the redox state of the plastoquinone pool. The significance of these plastid transcriptional responses and the identity of the underlying genetic control systems are discussed with relevance to diatom photosynthetic acclimation.