Foghpaul1871

Direct provision of personnel to assist in the NHS' clinical output served to foster mutually beneficial interorganisational relationships, while providing objective benefit for the UK public.This paper was selected as the BMJ Military Health Royal Society of Medicine Colt Foundation National Essay Prize Winner 2021.Necrotising enterocolitis (NEC) is a severe gastrointestinal disease mostly in premature infants due to intestinal necrosis. The aetiology of NEC is multifactorial and includes gut immaturity, intestinal dysbiosis and exaggerated intestinal mucosal reactivity to microbial ligands. Radiographic evidence of pneumatosis intestinalis has been a critical feature for diagnosing NEC Bell stage ≥IIA and recommended treatment includes prolonged antibiotics (7-14 days) while off enteral feeds. Pneumatosis coli (Pcoli), a mild or benign form of NEC, is characterised by pneumatosis limited to the colon in an infant having haematochezia, negative septic screening and no systemic signs. We report two healthy preterm infants with haematochezia and colonic pneumatosis while on breast milk feeds. The sepsis screen was negative. A brief period of antibiotics and gut rest led to the spontaneous resolution of haematochezia and colonic pneumatosis, facilitating early enteral feeds. This case report emphasises the need to differentiate NEC from benign Pcoli.

Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.

The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.

The authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr

) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.

LO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. learn more The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, invivo near-infrared fluorescence molecular tomographic imaging, and exvivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr

mice, in the vicinity of macrophages.

The authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.

The authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.

Guidelines for evaluating patients with suspected coronary artery disease (CAD) recommend pretest probability (PTP) estimation but provide no clear recommendations regarding diagnostic testing in patients with >5% to 15% risk of obstructive CAD. The diagnostic and prognostic value of PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS) calculation in this patient group is unknown.

This work aims to improve the evaluation of stable patients with suspected CAD by using the PMRS, which identifies patients at minimal risk of CAD and events in patients with >5% to 15% PTP of obstructive CAD.

Greater than 5% to 15% PTP patients from 2 large clinical trials were used for subcohort derivation PROMISE (N=10,003) and Dan-NICAD (Danish study of Non-Invasive Testing in Coronary Artery Disease) (N=3,252). First, the PMRS cutoff associated with a prevalence of obstructive CAD≤5% was determined in the >5% to 15% PTP PROMISE core lab computed tomographic angiogvery low prevalence of obstructive CAD and adverse events. The proposed strategy may improve risk stratification and help reduce unneeded diagnostic testing.

5% to 15% PTP patients into a group with very low prevalence of obstructive CAD and adverse events. The proposed strategy may improve risk stratification and help reduce unneeded diagnostic testing.

Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD).

The authors determined whether biomarkers of inflammation and myocardial injury-interleukin (IL)-6 and high-sensitivity cardiac troponin (hs-cTn)-were associated with the presence and extent of CAD and were independent predictors of major adverse cardiovascular events (MACEs) in stable chest pain.

Using participants from the PROMISE trial, the authors measured hs-cTn I and IL-6 concentrations and analyzed computed tomography angiography (CTA) images in the core laboratory for CAD characteristics significant stenosis (≥70%), high-risk plaque (HRP), Coronary Artery Disease Reporting and Data System (CAD-RADS) categories, segment involvement score (SIS), and coronary artery calcium (CAC) score. The primary endpoint was a composite MACE (death, myocardial infarction, or unstable angina).

The authors included 1,796 participants (age 60.2 ± 8.0 years; 47.5% men, ach contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs, indicating that myocardial injury and inflammation may each contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

Noninvasive functional imaging is often performed in patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA). However, the prognostic value of stress cardiac magnetic resonance (CMR) is unknown in patients with coronary stenosis of unknown significance on coronary CTA.

This study assessed the prognostic value of stress CMR in symptomatic patients with obstructive CAD of unknown significance on coronary CTA.

Between 2008 and 2020, consecutive symptomatic patients without known CAD referred for coronary CTA were screened. Patients with obstructive CAD (at least 1≥50% stenosis on coronary CTA) were further referred for stress CMR and followed for the occurrence of major adverse cardiovascular events (MACEs), defined as cardiovascular death or nonfatal myocardial infarction.

Of 2,210 patients who completed CMR, 2,038 (46.5% men; mean age 69.8 ± 12.2 years) completed follow-up (median 6.8 years; IQR 5.9-9.2 years); 281 experienced a MACE (13.8%). Inducible incremental prognostic value to predict MACEs.

Current guidelines distinguish stage B heart failure (SBHF) (asymptomatic left ventricular [LV] dysfunction) from stage A heart failure (SAHF) (asymptomatic with heart failure [HF] risk factors) on the basis of myocardial infarction, LV remodeling (hypertrophy or reduced ejection fraction [EF]) or valvular disease. However, subclinical HF with preserved EF may not be identified with these criteria.

The purpose of this study was to assess the prediction of incident HF with global longitudinal strain (GLS) in patients with SAHF and SBHF.

The authors analyzed echocardiograms (including GLS) in 447 patients (age 65 ± 11 years; 77% male) enrolled in a prospective study of HF in individuals at risk of incident HF, with normal or mildly impaired EF (≥40%). Long-term follow-up was obtained via data linkage. Analysis was performed using a competing risks model.

After a median of 9 years of follow-up, 50 (10%) of the 447 patients had new HF admissions, and 87 (18%) died. In multivariable analysis, all imaging v of SBHF for the prediction of subsequent HF admissions.

Echocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment-related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation.

This work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD.

In this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regressiange.

GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).Predicting the structure (or pose) of RNA-ligand complexes is an important problem in RNA structural biology. Although one could use computational docking to rapidly sample putative poses of RNA-ligand complexes, accurately discriminating the native-like poses from non-native, decoy poses remains a formidable challenge. Here, we started from the assumption that native-like RNA-ligand poses are less likely to dissociate during molecular dynamics simulations, and then we used enhanced simulations to promote ligand unbinding for diverse poses of a handful of RNA aptamer-ligand complexes. By fitting unbinding profiles obtained from the simulations to a single exponential, we identified the characteristic decay time (τ) as particularly effective at resolving native poses from decoys. We also found that a simple regression model trained to predict the simulation-derived parameters directly from structure could also discriminate ligand poses for similar RNA aptamers. Characterizing the unbinding properties of individual poses may thus be an effective strategy for enhancing pose prediction for ligands interacting with RNA aptamers. A similar strategy might be applicable to other ligandable RNAs; however, further analysis will be required to confirm this hypothesis.