Single-stage repair of adult aortic coarctation and concomitant cardiovascular pathologies: a new alternative surgical approach

BACKGROUND: Coarctation of the aorta in the adulthood is sometimes associated with additional cardiovascular pathologies that require intervention. Ideal approach in such patients is uncertain. Anatomic left-sided short aortic bypass from the arcus aorta to descending aorta via median sternotomy allows simultaneuos repair of both complex aortic coarctation and concomitant cardiac operation. MATERIALS: Four adult patients were underwent Anatomic left-sided short aortic bypass operation for complex aortic coarctation through median sternotomy using deep hypothermic circulatory arrest. Concomitant cardiac operations were Bentall procedure for annuloaortic ectasia in one patient, coronary artery bypass grafting for three vessel disease in two patient, and patch closure of ventricular septal defect in one patient. RESULTS: All patients survived the operation and were alive with patent bypass at a mean follow-up of 36 months. No graft-related complications occurred, and there were no instances of stroke or paraplegia. CONCLUSION: We conclude that single-stage repair of adult aortic coarctation with concomitant cardiovascular lesions can be performed safely using this newest technique

Double conditional human embryonic kidney cell line based on FLP and ΦC31 mediated transgene integration

<p>Abstract</p> <p>Background</p> <p>FLP recombinase mediated integration into a pre-integrated FRT site is routinely used to generate highly reproducible stable transgenic cell lines. In this study, we broaden the system of site specific integration by introducing ΦC31 integrase mediated integration into attP sites.</p> <p>Results</p> <p>We generated a HEK293 host cell line with a single copy FRT as well as an attP site allowing site specific integration of two distinct transgenes. To achieve conditional control, we used the tetracycline and Shld1 inducible systems. By introducing fluorescent reporters we show that integration and induction of two transgenes are completely independent. We applied this new technique to investigate the effect of HNF4α on proliferation of HEK293 cells by introducing HNF4α into each integration site. We obtained in two independent cell lines highly reproducible results that prove the usefulness of this novel HEK-attP/FRT cell line.</p> <p>Conclusions</p> <p>In this study we have established and applied a HEK-attP/FRT cell line that allows site specific integration of two conditional transgenes using the FLP recombinase as well as the ΦC31 integrase.</p

Decomposers and root feeders interactively affect plant defence in Sinapis alba

Aboveground herbivory is well known to change plant growth and defence. In contrast, effects of soil organisms, acting alone or in concert, on allocation patterns are less well understood. We investigated separate and combined effects of the endogeic earthworm species Aporrectodea caliginosa and the root feeding nematode species Pratylenchus penetrans and Meloidogyne incognita on plant responses including growth and defence metabolite concentrations in leaves of white mustard, Sinapis alba. Soil biota had a strong impact on plant traits, with the intensity varying due to species combinations. Nematode infestation reduced shoot biomass and nitrogen concentration but only in the absence of earthworms. Earthworms likely counteracted the negative effects of nematodes. Infestation with the migratory lesion-nematode P. penetrans combined with earthworms led to increased root length. Earthworm biomass increased in the presence of this species, indicating that these nematodes increased the food resources of earthworms—presumably dead and decaying roots. Nitrogen-based defence compounds, i.e. glucosinolates, did not correlate with nitrogen levels. In the presence of earthworms, concentrations of aromatic glucosinolates in leaves were significantly increased. In contrast, infection with P. penetrans strongly decreased concentrations of glucosinolates (up to 81%). Infestation with the sedentary nematode M. incognita induced aromatic glucosinolates by more than 50% but only when earthworms were also present. Myrosinase activities, glucosinolate-hydrolysing enzymes, were unaffected by nematodes but reduced in the presence of earthworms. Our results document that root-feeding nematodes elicit systemic plant responses in defence metabolites, with the responses varying drastically with nematode species of different functional groups. Furthermore, systemic plant responses are also altered by decomposer animals, such as earthworms, challenging the assumption that induction of plant responses including defence traits is restricted to herbivores. Soil animals even interact and modulate the individual effects on plant growth and plant defence, thereby likely also influencing shoot herbivore attack

Combining Optimal Control Theory and Molecular Dynamics for Protein Folding

A new method to develop low-energy folding routes for proteins is presented. The novel aspect of the proposed approach is the synergistic use of optimal control theory with Molecular Dynamics (MD). In the first step of the method, optimal control theory is employed to compute the force field and the optimal folding trajectory for the atoms of a Coarse-Grained (CG) protein model. The solution of this CG optimization provides an harmonic approximation of the true potential energy surface around the native state. In the next step CG optimization guides the MD simulation by specifying the optimal target positions for the atoms. In turn, MD simulation provides an all-atom conformation whose positions match closely the reference target positions determined by CG optimization. This is accomplished by Targeted Molecular Dynamics (TMD) which uses a bias potential or harmonic restraint in addition to the usual MD potential. Folding is a dynamical process and as such residues make different contacts during the course of folding. Therefore CG optimization has to be reinitialized and repeated over time to accomodate these important changes. At each sampled folding time, the active contacts among the residues are recalculated based on the all-atom conformation obtained from MD. Using the new set of contacts, the CG potential is updated and the CG optimal trajectory for the atoms is recomputed. This is followed by MD. Implementation of this repetitive CG optimization - MD simulation cycle generates the folding trajectory. Simulations on a model protein Villin demonstrate the utility of the method. Since the method is founded on the general tools of optimal control theory and MD without any restrictions, it is widely applicable to other systems. It can be easily implemented with available MD software packages

Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics

We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to the common ‘spaghetti-like’ structures but to dense matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance, these morphological indicators may have prognostic value.Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) of South Africa.http://www.cardiab.com/hb201

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

National identity predicts public health support during a global pandemic (vol 13, 517, 2022) : National identity predicts public health support during a global pandemic (Nature Communications, (2022), 13, 1, (517), 10.1038/s41467-021-27668-9)

Publisher Copyright: © The Author(s) 2022.In this article the author name ‘Agustin Ibanez’ was incorrectly written as ‘Augustin Ibanez’. The original article has been corrected.Peer reviewe

National identity predicts public health support during a global pandemic.

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics