Triple arginines in the cytoplasmic tail of endomannosidase are not essential for type II membrane topology and Golgi localization

Abstract.: Endomannosidase is a Golgi-localized endoglycosidase, which provides an alternate glucosidase-independent pathway of glucose trimming. Using a protease protection assay we demonstrated that Golgi-endomannosidase is a type II membrane protein. The first 25 amino acids of this protein, containing the cytoplasmic tail and the transmembrane domain, were sufficient for Golgi retention of fused reporter proteins α1-antitrypsin or green fluorescent protein. However, shortening or deletion of the transmembrane domain prevented Golgi localization, while lengthening it partially reduced Golgi retention of the enzyme. Substitution of the highly conserved positively charged amino acids within the cytoplasmic tail had neither an effect on type II topology nor on the inherent Golgi localization of the enzyme. In contrast, cytoplasmic tail-deleted rat endomannosidase possessed an inverted topology resulting in endoplasmic reticulum mislocalization. Thus, proper topology rather than the presence of positively charged amino acids in the cytoplasmic tail is critical for Golgi localization of rat endomannosidas

Sex differences in treatment and outcomes of patients with in-hospital ST-elevation myocardial infarction.

BACKGROUND AND HYPOTHESIS Two cohorts face high mortality after ST-elevation myocardial infarction (STEMI): females and patients with in-hospital STEMI. The aim of this study was to evaluate sex differences in ischemic times and outcomes of in-hospital STEMI patients. METHODS Consecutive STEMI patients treated with percutaneous coronary intervention (PCI) were prospectively recruited from 30 hospitals into the Victorian Cardiac Outcomes Registry (2013-2018). Sex discrepancies within in-hospital STEMIs were compared with out-of-hospital STEMIs. The primary endpoint was 12-month all-cause mortality. Secondary endpoints included symptom-to-device (STD) time and 30-day major adverse cardiovascular events (MACE). To investigate the relationship between sex and 12-month mortality for in-hospital versus out-of-hospital STEMIs, an interaction analysis was included in the multivariable models. RESULTS A total of 7493 STEMI patients underwent PCI of which 494 (6.6%) occurred in-hospital. In-hospital versus out-of-hospital STEMIs comprised 31.9% and 19.9% females, respectively. Female in-hospital STEMIs were older (69.5 vs. 65.9 years, p = .003) with longer adjusted geometric mean STD times (104.6 vs. 94.3 min, p < .001) than men. Female versus male in-hospital STEMIs had no difference in 12-month mortality (27.1% vs. 20.3%, p = .92) and MACE (22.8% vs. 19.3%, p = .87). Female sex was not independently associated with 12-month mortality for in-hospital STEMIs which was consistent across the STEMI cohort (OR: 1.26, 95% CI: 0.94-1.70, p = .13). CONCLUSIONS In-hospital STEMIs are more frequent in females relative to out-of-hospital STEMIs. Despite already being under medical care, females with in-hospital STEMIs experienced a 10-min mean excess in STD time compared with males, after adjustment for confounders. Adjusted 12-month mortality and MACE were similar to males

Differences in outcomes of patients with in-hospital versus out-of-hospital ST-elevation myocardial infarction: a registry analysis

OBJECTIVES Patients with ST-elevation myocardial infarction (STEMI) that occur while already in hospital ('in-hospital STEMI') face high mortality. However, data about this patient population are scarce. We sought to investigate differences in reperfusion and outcomes of in-hospital versus out-of-hospital STEMI. DESIGN, SETTING AND PARTICIPANTS Consecutive patients with STEMI all treated with percutaneous coronary intervention (PCI) across 30 centres were prospectively recruited into the Victorian Cardiac Outcomes Registry (2013-2018). PRIMARY AND SECONDARY OUTCOMES Patients with in-hospital STEMI were compared with patients with out-of-hospital STEMI with a primary endpoint of 30-day major adverse cardiovascular events (MACE). Secondary endpoints included ischaemic times, all-cause mortality and major bleeding. RESULTS Of 7493 patients with PCI-treated STEMI, 494 (6.6%) occurred in-hospital. Patients with in-hospital STEMI were older (67.1 vs 62.4 years, p<0.001), more often women (32% vs 19.9%, p<0.001), with more comorbidities. Patients with in-hospital STEMI had higher 30-day MACE (20.4% vs 9.8%, p<0.001), mortality (12.1% vs 6.9%, p<0.001) and major bleeding (4.9% vs 2.3%, p<0.001), than patients with out-of-hospital STEMI. According to guideline criteria, patients with in-hospital STEMI achieved symptom-to-device times of ≤70 min and ≤90 min in 29% and 47%, respectively. Patients with out-of-hospital STEMI achieved door-to-device times of ≤90 min in 71%. Occurrence of STEMI while in hospital independently predicted higher MACE (adjusted OR 1.77, 95% CI 1.33 to 2.36, p<0.001) and 12-month mortality (adjusted OR 1.49, 95% CI 1.08 to 2.07, p<0.001). CONCLUSIONS Patients with in-hospital STEMI experience delays to reperfusion with significantly higher MACE and mortality, compared with patients with out-of-hospital STEMI, after adjustment for confounders. Focused strategies are needed to improve recognition and outcomes in this high-risk and understudied population

Amplitude and frequency sensing of microwave fields with a superconducting transmon qudit

Experiments with superconducting circuits require careful calibration of the applied pulses and fields over a large frequency range. This remains an ongoing challenge as commercial semiconductor electronics are not able to probe signals arriving at the chip due to its cryogenic environment. Here, we demonstrate how the on-chip amplitude and frequency of a microwave signal can be inferred from the ac Stark shifts of higher transmon levels. In our time-resolved measurements we employ Ramsey fringes, allowing us to detect the amplitude of the systems transfer function over a range of several hundreds of MHz with an energy sensitivity on the order of 10−4. Combined with similar measurements for the phase of the transfer function, our sensing method can facilitate pulse correction for high fidelity quantum gates in superconducting circuits. Additionally, the potential to characterize arbitrary microwave fields promotes applications in related areas of research, such as quantum optics or hybrid microwave systems including photonic, mechanical or magnonic subsystems

Sex differences in prehospital delays in patients with st-segment-elevation myocardial infarction undergoing percutaneous coronary intervention

BACKGROUND: Women with ST-segment-elevation myocardial infarction experience delays in reperfusion compared with men with little data on each time component from symptom onset to reperfusion. This study analyzed sex discrepancies in patient delays, prehospital system delays, and hospital delays. METHODS AND RESULTS: Consecutive patients with ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention across 30 hospitals in the Victorian Cardiac Outcomes Registry (2013-2018) were analyzed. Data from the Ambulance Victoria Data warehouse were used to perform linkage to the Victorian Cardiac Outcomes Registry for all patients transported via emergency medical services (EMS). The primary end point was EMS call-to-door time (prehospital system delay). Secondary end points included symptom-to-EMS call time (patient delay), door-to-device time (hospital delay), 30-day mortality, major adverse cardiovascular events, and major bleeding. End points were analyzed according to sex and adjusted for age, comorbidities, cardiogenic shock, cardiac arrest, and symptom onset time. A total of 6330 (21% women) patients with ST-segment-elevation myocardial infarction were transported by EMS. Compared with men, women had longer adjusted geometric mean symptom-to-EMS call times (47.0 versus 44.0 minutes; P<0.001), EMS call-to-door times (58.1 versus 55.7 minutes; P<0.001), and door-to-device times (58.5 versus 54.9 minutes; P=0.006). Compared with men, women had higher 30-day mortality (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P=0.02) and major bleeding (OR, 1.54; 95% CI, 1.08-2.20; P=0.02). CONCLUSIONS: Female patients with ST-segment-elevation myocardial infarction experienced excess delays in patient delays, prehospital system delays, and hospital delays, even after adjustment for confounders. Prehospital system and hospital delays resulted in an adjusted excess delay of 10 minutes compared with men

Coronary Computed Tomographic Angiography at 80 kVp and Knowledge-Based Iterative Model Reconstruction Is Non-Inferior to that at 100 kVp with Iterative Reconstruction

The aims of this study were to compare the image noise and quality of coronary computed tomographic angiography (CCTA) at 80 kVp with knowledge-based iterative model reconstruction (IMR) to those of CCTA at 100 kVp with hybrid iterative reconstruction (IR), and to evaluate the feasibility of a low-dose radiation protocol with IMR. Thirty subjects who underwent prospective electrocardiogram-gating CCTA at 80 kVp, 150 mAs, and IMR (Group A), and 30 subjects with 100 kVp, 150 mAs, and hybrid IR (Group B) were retrospectively enrolled after sample-size calculation. A BMI of less than 25 kg/m2 was required for inclusion. The attenuation value and image noise of CCTA were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated at the proximal right coronary artery and left main coronary artery. The image noise was analyzed using a non-inferiority test. The CCTA images were qualitatively evaluated using a four-point scale. The radiation dose was significantly lower in Group A than Group B (0.69 ± 0.08 mSv vs. 1.39 ± 0.15 mSv, p < 0.001). The attenuation values were higher in Group A than Group B (p < 0.001). The SNR and CNR in Group A were higher than those of Group B. The image noise of Group A was non-inferior to that of Group B. Qualitative image quality of Group A was better than that of Group B (3.6 vs. 3.4, p = 0.017). CCTA at 80 kVp with IMR could reduce the radiation dose by about 50%, with non-inferior image noise and image quality than those of CCTA at 100 kVp with hybrid IR

Coronary dominance and prognosis in patients undergoing coronary computed tomographic angiography: results from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry

Aims Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA. Methods and results The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9 ± 12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD (HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance. Conclusion In our study population, survival after 5 years of follow-up did not differ significantly between patients with left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulation

Coronary dominance and prognosis in patients undergoing coronary computed tomographic angiography: Results from the CONFIRM (COronary CTAngiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter) registry

Aims: Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA. Methods and results: The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9±12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD(HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance. Conclusion: In our study population, survival after 5 years of follow-up did not differ significantly between patientswith left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study. Methods and results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9&nbsp;years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as &gt; 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3092€/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure. Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization

Early carboniferous brachiopod faunas from the Baoshan block, west Yunnan, southwest China

38 brachiopod species in 27 genera and subgenera are described from the Yudong Formation in the Shidian-Baoshan area, west Yunnan, southwest China. New taxa include two new subgenera: Unispirifer (Septimispirifer) and Brachythyrina (Longathyrina), and seven new species: Eomarginifera yunnanensis, Marginatia cylindrica, Unispirifer (Unispirifer) xiangshanensis, Unispirifer (Septimispirifer) wafangjieensis, Brachythyrina (Brachythyrina) transversa, Brachythyrina (Longathyrina) baoshanensis, and Girtyella wafangjieensis. Based on the described material and constraints from associated coral and conodont faunas, the age of the brachiopod fauna from the Yudon Formation is considered late Tournaisian (Early Carboniferous), with a possibility extending into earlyViseacutean.<br /