Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart

The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal development and cardiac function. Most cases of atrial septal defects and cardiomyopathy are not associated with a known causative gene, suggesting that further analysis into candidate genes is required. Expression studies localised eMYH in the developing chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner and functional studies were carried out using electrical and calcium signalling methodologies. Knockdown in the early embryo led to abnormal atrial septal development and heart enlargement. Intriguingly, action potentials of the eMYH knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy chain knockdowns and controls. Although myofibrillogenesis appeared normal, in knockdown hearts the tissue integrity was affected owing to apparent focal points of myocyte loss and an increase in cell death. An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy

Ambient-pressure endstation of the Versatile Soft X-ray (VerSoX) beamline at Diamond Light Source

The ambient-pressure endstation and branchline of the Versatile Soft X-ray (VerSoX) beamline B07 at Diamond Light Source serves a very diverse user community studying heterogeneous catalysts, pharmaceuticals and biomaterials under realistic conditions, liquids and ices, and novel electronic, photonic and battery materials. The instrument facilitates studies of the near-surface chemical composition, electronic and geometric structure of a variety of samples using X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectroscopy in the photon energy range from 170 eV to 2800 eV. The beamline provides a resolving power hν/Δ(hν) > 5000 at a photon flux > 1010 photons s−1 over most of its energy range. By operating the optical elements in a low-pressure oxygen atmosphere, carbon contamination can be almost completely eliminated, which makes the beamline particularly suitable for carbon K-edge NEXAFS. The endstation can be operated at pressures up to 100 mbar, whereby XPS can be routinely performed up to 30 mbar. A selection of typical data demonstrates the capability of the instrument to analyse details of the surface composition of solid samples under ambient-pressure conditions using XPS and NEXAFS. In addition, it offers a convenient way of analysing the gas phase through X-ray absorption spectroscopy. Short XPS spectra can be measured at a time scale of tens of seconds. The shortest data acquisition times for NEXAFS are around 0.5 s per data point

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

Summary 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 middleincome 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 lowincome 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 lowincome, 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

Pulmonary arterial hypertension in children with sickle cell anaemia

Background:Pulmonary hypertension(PHT) is a life threatening complication which occurs in adults with sickle cell disease(SCD). But there is paucity of knowledge about prevalence of pulmonary hypertension in Paediatric SCD population.Objective:To find out the prevalence of pulmonary hypertension in children with SCD.Methods:552 children age between 5 to 14 years were enrolled after written informed consent was obtained from parents/guardian. Children with Congenital heart disease, pulmonary stenosis, Rheumatic heart disease were excluded from the study. PHT in all cases of with SCD children was screened by using 2D Echocardiography in the department of cardiology. PHT is defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg at rest. All the data were validated and analyzed with SPSS version 25.Results:Overall prevalence of pulmonary hypertension in our study is 20.4%. Of these, 6.5% subjects have mild and 13.9% subjects have moderate pulmonary hypertension. Low haemoglobin (p=0.021), high number of crisis (p=0.000), high number of blood transfusion (p=0.000), presence of loud second heart sound (p=0.000) and presence of Parasternal heave (p=0.000) were significantly associated with pulmonary hypertension. The prevalence of pulmonary hypertension in children with SCD demonstrated an increase in trend with age.Conclusion:High pulmonary artery pressures do occur in children with SCD. Screening by echocardiography can lead to early detection and intervention

The role of 18F-FDG PET/CT in retroperitoneal sarcomas—A multicenter retrospective study

Background: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the evaluation of retroperitoneal sarcomas is poorly defined. We evaluated the correlation of maximum standardized uptake value (SUVmax) with pathologic tumor grade in the surgical specimen of primary retroperitoneal dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS). Methods: Patients with the above histological subtypes in three participating institutions with preoperative 18F-FDG PET/CT scan and histopathological specimen available for review were included. The association between SUVmax and pathological grade was assessed. Correlation between SUVmax and relapse-free survival (RFS) and overall survival (OS) were also studied. Results: Of the total 58 patients, final pathological subtype was DDLPS in 44 (75.9%) patients and LMS in 14 (24.1%) patients. The mean SUVmax was 8.7 with a median 7.1 (range, 2.2–33.9). The tumors were graded I, II, III in 6 (10.3%), 35 (60.3%), and 17 (29.3%) patients, respectively. There was an association of higher histological grade with higher SUVmax (rs = 0.40, p =.002). Increasing SUVmax was associated with worse RFS (p =.003) and OS (p =.003). Conclusion: There is a correlation between SUVmax and pathologic tumor grade; increasing SUVmax was associated with worse OS and RFS, providing a preoperative noninvasive surrogate marker of tumor grade and biological behavior