Ligamentum arteriosum calcification on paediatric postmortem computed tomography.

BACKGROUND: Ligamentum arteriosum calcification may be a normal finding in some children, although the frequency has not been well described. OBJECTIVE: To estimate the frequency of ligamentum arteriosum calcification in children at postmortem imaging. MATERIALS AND METHODS: We conducted a single-centre retrospective review of paediatric postmortem CT and chest radiographic imaging over a 6-year period (January 2012 to December 2018). Two independent reviewers assessed the presence of calcification on imaging. We calculated descriptive statistical analysis of ligamentum arteriosum calcification frequency and association with age and gender. RESULTS: During the study period, 220 children underwent whole-body postmortem CT and 182 underwent radiographic imaging. The frequency was higher on postmortem CT than plain radiographs (67/220, 30.5% vs. 3/182, 1.6%) and was highest in children ages 1-7 years (53.6-66.7%), with gradual reduction in frequency in older children, and none in children older than 12 years. There was no gender predilection. CONCLUSION: In the postmortem setting, ligamentum arteriosum calcification is a common finding in children <8 years of age. It can be better identified on postmortem CT than chest radiographs. Radiologists new to reporting postmortem paediatric CT studies should recognise this as a common normal finding to avoid unnecessary further investigations at autopsy

The quality control theory of aging

The quality control (QC) theory of aging is based on the concept that aging is the result of a reduction in QC of cellular systems designed to maintain lifelong homeostasis. Four QC systems associated with aging are 1) inadequate protein processing in a distressed endoplasmic reticulum (ER); 2) histone deacetylase (HDAC) processing of genomic histones and gene silencing; 3) suppressed AMPK nutrient sensing with inefficient energy utilization and excessive fat accumulation; and 4) beta-adrenergic receptor (BAR) signaling and environmental and emotional stress. Reprogramming these systems to maintain efficiency and prevent aging would be a rational strategy for increased lifespan and improved health. The QC theory can be tested with a pharmacological approach using three well-known and safe, FDA-approved drugs: 1) phenyl butyric acid, a chemical chaperone that enhances ER function and is also an HDAC inhibitor, 2) metformin, which activates AMPK and is used to treat type 2 diabetes, and 3) propranolol, a beta blocker which inhibits BAR signaling and is used to treat hypertension and anxiety. A critical aspect of the QC theory, then, is that aging is associated with multiple cellular systems that can be targeted with drug combinations more effectively than with single drugs. But more importantly, these drug combinations will effectively prevent, delay, or reverse chronic diseases of aging that impose such a tremendous health burden on our society

Chest radiographs versus CT for the detection of rib fractures in children (DRIFT): a diagnostic accuracy observational study

BACKGROUND: Internationally, chest radiography is the standard investigation for identifying rib fractures in suspected physical abuse in infants. Several small observation studies in children have found that chest CT can provide greater accuracy than radiography for fracture detection, potentially aiding medicolegal proceedings in abuse cases; however, to our knowledge, this greater accuracy has not been comprehensively evaluated. We aimed to determine differences in rib fracture detection rates between post-mortem chest radiographs and chest CT images, using forensic autopsy as the reference standard. METHODS: In this retrospective diagnostic accuracy study, we searched the Great Ormond Street Hospital (London, UK) radiology information system for all children aged 0-16 years who had a post-mortem skeletal survey (ie, full-body radiography), CT, and full autopsy between Jan 1, 2012, and Jan 1, 2017, for a purpose of death investigation. Cases were excluded if the imaging was done for a reason other than a forensic investigation or if image quality was suboptimal. Radiologists were recruited as reporters on a voluntary basis via membership databases from international radiology and post-mortem imaging societies with no specific inclusion or exclusion criteria. Reporters were sent a set of chest radiographs on a password protected and encrypted USB flash drive or via a secure filesharing website and independently reported on the presence of rib fractures, fracture location, and the confidence level of their interpretation. They were masked to the clinical information of the images. 1 month later, the same reporters were sent CTs for the same cases in a random order and asked to report on the same features. The primary objective was to compare the accuracy of detection of rib fractures by use of post-mortem chest radiographs and CTs, with autopsy data as reference standard. Accuracy was assessed by comparison of diagnostic statistics, calculated using random-intercept multilevel logistic models with reporter and patient included as cross-classified random-effects. FINDINGS: 25 cases of children (aged 1 month to 7 years), with 136 rib fractures at autopsy with paired post-mortem chest radiographs and CTs, were selected for analysis. 38 radiologists were recruited as reporters from 23 international centres; 12 (32%) were consultants, median experience of 14·5 years (range 6-27), and 26 (68%) were registrars, median experience of 4 years (range 2-9). Across all radiologists, three times as many rib fractures were correctly detected by use of chest CTs compared with chest radiography (sensitivity 44·9% [95% CI 31·7-58·9] vs 13·5% [8·1-21·5]; difference 31·4% [23·3-37·8; p<0·001]). Sensitivity for detection on the correct rib was higher by use of CT than by use of radiography (62·4% [95% CI 44·9-77·1] vs 23·1% [12·9-37·8]; difference 39·3% [31·9-42·2; p<0·001]), as was diagnosis of a patient with any rib fracture or fractures (81·5% [75·8-86·0] vs 64·7% [57·3-71·4]; difference 16·7% [11·5-22·2; p<0·001]). Radiologist confidence was higher when using CT images than radiographs (highest confidence rating given on 3317 [63·6%] of 5218 fractures for CT vs 1518 [46·6%] of 3303 on radiographs) and was a predictor for accurate fracture detection. INTERPRETATION: Chest CT provides greater accuracy than conventional chest radiography for post-mortem rib fracture detection, irrespective of radiologist experience or fracture location, although both methods detected a substantial number of false positives. The diagnostic accuracy of CT should be studied further in live children ideally in a multicentre trial to assess the applicability of our results. FUNDING: Great Ormond Street Children's Charity, Medical Research Council, Royal College of Radiologists, Research Councils UK, National Institute for Health Research

Use of local anaesthetics and adjuncts for spinal and epidural anaesthesia and analgesia at German and Austrian University Hospitals: an online survey to assess current standard practice

<p>Abstract</p> <p>Background</p> <p>The present anonymous multicenter online survey was conducted to evaluate the application of regional anaesthesia techniques as well as the used local anaesthetics and adjuncts at German and Austrian university hospitals.</p> <p>Methods</p> <p>39 university hospitals were requested to fill in an online questionnaire, to determine the kind of regional anaesthesia and preferred drugs in urology, obstetrics and gynaecology.</p> <p>Results</p> <p>33 hospitals responded. No regional anaesthesia is conducted in 47% of the minor gynaecological and 44% of the urological operations; plain bupivacaine 0.5% is used in 38% and 47% respectively. In transurethral resections of the prostate and bladder no regional anaesthesia is used in 3% of the responding hospitals, whereas plain bupivacaine 0.5% is used in more than 90%. Regional anaesthesia is only used in selected major gynaecological and urological operations. On the contrary to the smaller operations, the survey revealed a large variety of used drugs and mixtures. Almost 80% prefer plain bupivacaine or ropivacaine 0.5% in spinal anaesthesia in caesarean section. Similarly to the use of drugs in major urological and gynaecological operations a wide range of drugs and adjuncts is used in epidural anaesthesia in caesarean section and spontaneous delivery.</p> <p>Conclusions</p> <p>Our results indicate a certain agreement in short operations in spinal anaesthesia. By contrast, a large variety concerning the anaesthesiological approach in larger operations as well as in epidural analgesia in obstetrics could be revealed, the causes of which are assumed to be primarily rooted in particular departmental structures.</p

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Microbiological profiles of sputum and gastric juice aspirates in Cystic Fibrosis patients.

Gastro-Oesophageal Reflux (GOR) is a key problem in Cystic Fibrosis (CF), but the relationship between lung and gastric microbiomes is not well understood. We hypothesised that CF gastric and lung microbiomes are related. Gastric and sputum cultures were obtained from fifteen CF patients receiving percutaneous endoscopic gastrostomy feeding. Non-CF gastric juice data was obtained through endoscopy from 14 patients without lung disease. Bacterial and fungal isolates were identified by culture. Molecular bacterial profiling used next generation sequencing (NGS) of the 16S rRNA gene. Cultures grew bacteria and/or fungi in all CF gastric juice and sputa and in 9/14 non-CF gastric juices. Pseudomonas aeruginosa(Pa) was present in CF sputum in 11 patients, 4 had identical Pa strains in the stomach. NGS data from non-CF gastric juice samples were significantly more diverse compared to CF samples. NGS showed CF gastric juice had markedly lower abundance of normal gut bacteria; Bacteroides and Faecalibacterium, but increased Pseudomonas compared with non-CF. Multivariate partial least squares discriminant analysis demonstrated similar bacterial profiles of CF sputum and gastric juice samples, which were distinct from non-CF gastric juice. We provide novel evidence suggesting the existence of an aerodigestive microbiome in CF, which may have clinical relevance

Treatment of Peritoneal Carcinomatosis by Targeted Delivery of the Radio-Labeled Tumor Homing Peptide 213Bi-DTPA-[F3]2 into the Nucleus of Tumor Cells

BACKGROUND: Alpha-particle emitting isotopes are effective novel tools in cancer therapy, but targeted delivery into tumors is a prerequisite of their application to avoid toxic side effects. Peritoneal carcinomatosis is a widespread dissemination of tumors throughout the peritoneal cavity. As peritoneal carcinomatosis is fatal in most cases, novel therapies are needed. F3 is a tumor homing peptide which is internalized into the nucleus of tumor cells upon binding to nucleolin on the cell surface. Therefore, F3 may be an appropriate carrier for alpha-particle emitting isotopes facilitating selective tumor therapies. PRINCIPAL FINDINGS: A dimer of the vascular tumor homing peptide F3 was chemically coupled to the alpha-emitter (213)Bi ((213)Bi-DTPA-[F3](2)). We found (213)Bi-DTPA-[F3](2) to accumulate in the nucleus of tumor cells in vitro and in intraperitoneally growing tumors in vivo. To study the anti-tumor activity of (213)Bi-DTPA-[F3](2) we treated mice bearing intraperitoneally growing xenograft tumors with (213)Bi-DTPA-[F3](2). In a tumor prevention study between the days 4-14 after inoculation of tumor cells 6x1.85 MBq (50 microCi) of (213)Bi-DTPA-[F3](2) were injected. In a tumor reduction study between the days 16-26 after inoculation of tumor cells 6x1.85 MBq of (213)Bi-DTPA-[F3](2) were injected. The survival time of the animals was increased from 51 to 93.5 days in the prevention study and from 57 days to 78 days in the tumor reduction study. No toxicity of the treatment was observed. In bio-distribution studies we found (213)Bi-DTPA-[F3](2) to accumulate in tumors but only low activities were found in control organs except for the kidneys, where (213)Bi-DTPA-[F3](2) is found due to renal excretion. CONCLUSIONS/SIGNIFICANCE: In conclusion we report that (213)Bi-DTPA-[F3](2) is a novel tool for the targeted delivery of alpha-emitters into the nucleus of tumor cells that effectively controls peritoneal carcinomatosis in preclinical models and may also be useful in oncology

Hydrophobicity and Charge Shape Cellular Metabolite Concentrations

What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108) of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ∼100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts

Parental rating of sleep in children with attention deficit/hyperactivity disorder

Objective: Sleep problems have often been associated with attention deficit/hyperactivity disorder (ADHD). Parents of those with ADHD and children with ADHD report sleep difficulties more frequently than healthy children and their parents. The primary objective of this paper is to describe sleep patterns and problems of 5 to 11-year-old children suffering from ADHD as described by parental reports and sleep questionnaires. Method: The study included 321 children aged 5–11 years (average age 8.4 years); 45 were diagnosed with ADHD, 64 had other psychiatric diagnoses, and 212 were healthy. One hundred and ninety-six of the test subjects were boys and 125 were girls. A semi-structured interview (Kiddie-SADS-PL) was used to DSM-IV diagnose ADHD and comorbidity in the clinical group. Sleep difficulties were rated using a structured sleep questionnaire (Children Sleep Behaviour Scale). Results: Children diagnosed with ADHD had a significantly increased occurrence of sleep problems. Difficulties relating to bedtime and unsettled sleep were significantly more frequent in the ADHD group than in the other groups. Children with ADHD showed prolonged sleep onset latency, but no difference was shown regarding numbers of awakenings per night and total sleep time per night. Comorbid oppositional defiant disorder appeared not to have an added effect on problematic behaviour around bedtime. Conclusion: Parents of children with ADHD report that their children do not sleep properly more often than other parents. The ADHD group report problems with bedtime resistance, problems with sleep onset latency, unsettled sleep and nightmares more often than the control groups. It may therefore be relevant for clinicians to initiate a closer examination of those cases reporting sleep difficulties