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Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic. We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs. Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37–43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13–20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38–46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12–29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29–45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2–9) in 2019 to 3 days (1–5) by the end of March, 2020. Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses. UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.

Aims/hypothesis The aim of this prospective nationwide study was to examine antenatal pregnancy care and pregnancy outcomes in women with type 1 and type 2 diabetes, and to describe changes since 2002/2003. Methods This national population-based cohort included 3036 pregnant women with diabetes from 155 maternity clinics in England and Wales who delivered during 2015. The main outcome measures were maternal glycaemic control, preterm delivery (before 37 weeks), infant large for gestational age (LGA), and rates of congenital anomaly, stillbirth and neonatal death. Results Of 3036 women, 1563 (51%) had type 1, 1386 (46%) had type 2 and 87 (3%) had other types of diabetes. The percentage of women achieving HbA 1c  < 6.5% (48 mmol/mol) in early pregnancy varied greatly between clinics (median [interquartile range] 14.3% [7.7–22.2] for type 1, 37.0% [27.3–46.2] for type 2). The number of infants born preterm (21.7% vs 39.7%) and LGA (23.9% vs 46.4%) were lower for women with type 2 compared with type 1 diabetes (both p  < 0.001). The prevalence rates for congenital anomaly (46.2/1000 births for type 1, 34.6/1000 births for type 2) and neonatal death (8.1/1000 births for type 1, 11.4/1000 births for type 2) were unchanged since 2002/2003. Stillbirth rates are almost 2.5 times lower than in 2002/2003 (10.7 vs 25.8/1000 births for type 1, p  = 0.0012; 10.5 vs 29.2/1000 births for type 2, p  = 0.0091). Conclusions/interpretation Stillbirth rates among women with type 1 and type 2 diabetes have decreased since 2002/2003. Rates of preterm delivery and LGA infants are lower in women with type 2 compared with type 1 diabetes. In women with type 1 diabetes, suboptimal glucose control and high rates of perinatal morbidity persist with substantial variations between clinics. Data availability Further details of the data collection methodology, individual clinic data and the full audit reports for healthcare professionals and service users are available from http://content.digital.nhs.uk/npid .

The analytical toolkit developed for investigations into water-soluble protein folding has yet to be applied in earnest to membrane proteins. A major problem is the difficulty in collecting kinetic data, which are crucial to understanding any reaction. Here, we combine kinetic and thermodynamic studies of the reversible unfolding of an α-helical membrane protein to provide a definitive value for the reaction free energy and a means to probe the transition state. Our analyses show that the major unfolding step in the SDS-induced denaturation of bacteriorhodopsin involves a reduction in α-helical structure and proceeds with a large free-energy change; both our equilibrium and kinetic measurements predict that the free energy of unfolding in the absence of denaturant is +20 kcal·mol⁻¹, with an associated m-value of 25 kcal·mol⁻¹. The rate of unfolding in the absence of denaturant,$k_{{\\rm u}}^{{\\rm H}_{2}{\\rm O}}$, is surprisingly very slow (≈10⁻¹⁵ s⁻¹). The kinetics also give information on the transition state for this major unfolding step, with a value for$\\beta \\ (m_{{\\rm f}}/[m_{{\\rm f}}+m_{{\\rm u}}])$of ≈0.1, indicating that the transition state is close to the unfolded state. We thus present a basis for mapping the structural and energetic properties of membrane protein folding by mutagenesis and classical kinetics.

The Kremlin is denying allegations that they may have been complicit in the delivery of chemical weapons; In Sweden a manhunt is still underway for the driver of Friday's Stockholm truck attack. The U.S. Congress are split over whether the Trump should launch any further full-scale war in the Middle East; Launching airstrikes in Syria dramatically changed the tone for Trump's first meeting with Chinese President Xi Jinping; The Russian president Vladimir Putin calls the U.S. military strike in Syria a serious blow to relations between Moscow and Washington and he denounced the strike as \"an aggression and a violation of international war\"; Punitive strikes have been used by a long line of U.S. presidents to punish or to warn others when their actions are deemed a threat to American interests.

Biology relies on the precise self-assembly of its molecular components. Generic principles of protein folding have emerged from extensive studies on small, water-soluble proteins, but it is unclear how these ideas are translated into more complex situations. In particular, the one-third of cellular proteins that reside in biological membranes will not fold like water-soluble proteins because membrane proteins need to expose, not hide, their hydrophobic surfaces. Here, we apply the powerful protein engineering method of Φ-value analysis to investigate the folding transition state of the alpha-helical membrane protein, bacteriorhodopsin, from a partially unfolded state. Our results imply that much of helix B of the seven-transmembrane helical protein is structured in the transition state with single-point alanine mutations in helix B giving Φ values >0.8. However, residues Y43 and T46 give lower Φ values of 0.3 and 0.5, respectively, suggesting a possible reduction in native structure in this region of the helix. Destabilizing mutations also increase the activation energy of folding, which is accompanied by an apparent movement of the transition state toward the partially unfolded state. This apparent transition state movement is most likely due to destabilization of the structured, unfolded state. These results contrast with the Hammond effect seen for several water-soluble proteins in which destabilizing mutations cause the transition state to move toward, and become closer in energy to, the folded state. We thus introduce a classic folding analysis method to membrane proteins, providing critical insight into the folding transition state.

Defining the structural features of a transition state is important in understanding a folding reaction. Here, we use Φ-value and double mutant analyses to probe the folding transition state of the membrane protein bacteriorhodopsin. We focus on the final C-terminal helix, helix G, of this seven transmembrane helical protein. Φ-values could be derived for 12 amino acid residues in helix G, most of which have low or intermediate values, suggesting that native structure is disrupted at these amino acid positions in the transition state. Notably, a cluster of residues between E204 and M209 all have Φ-values close to zero. Disruption of helix G is further confirmed by a low Φ-value of 0.2 between residues T170 on helix F and S226 on helix G, suggesting the absence of a native hydrogen bond between helices F and G. Φ-values for paired mutations involved in four interhelical hydrogen bonds revealed that all but one of these bonds is absent in the transition state. The unstructured helix G contrasts with Φ-values along helix B that are generally high, implying native structure in helix B in the transition state. Thus helix B seems to constitute part of a stable folding nucleus while the consolidation of helix G is a relatively late folding event. Polarization of secondary structure correlates with sequence position, with a structured helix B near the N terminus contrasting with an unstructured C-terminal helix G.

The Kremlin is denying allegations that they may have been complicit in the delivery of chemical weapons; In Sweden a manhunt is still underway for the driver of Friday's Stockholm truck attack. President Trump's swift action in Syria is a major shift in policy towards the nation; Launching airstrikes in Syria dramatically changed the tone for Trump's first meeting with Chinese President Xi Jinping; It all began in 2011 with children writing anti-government graffiti and it quickly escalated into a brutal Syrian government crackdown.