Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

The generation and propagation of atmospheric gravity waves observed during the Worldwide Atmospheric Gravity-wave Study (WAGS)

During the Worldwide Atmospheric Gravity-wave Study (WAGS) in October 1985, the EISCAT incoherent scatter radar was used to observe the generation of atmospheric gravity waves in the auroral zone in conjunction with a network of magnetometers and riometers. At the same time a chain of five ionosondes, an HF-Doppler system, a meteor radar and a radio telescope array were used to monitor any waves propagating southwards over the U.K. The EISCAT measurements indicated that in the evening sector both Joule heating and Lorentz forcing were sufficiently strong to generate waves, and both frequently showed an intrinsic periodicity caused by periodic variation in the magnetospheric electric field. Two occasions have been examined in detail where the onset of a source with intrinsic periodicity was followed by a propagating wave of the same period which was detected about an hour later, travelling southwards at speeds of over 300 m s−1, by the ionosondes and the HF-Doppler radar. In both cases the delay in arrival was consistent with the observed velocity, which suggests a direct relationship between a source in the auroral zone and a wave observed at mid-latitude

The musculoskeletal abnormalities of the Similaun Iceman (“ÖTZI”): clues to chronic pain and possible treatments

BACKGROUND AND INTRODUCTION: In 1991, a deceased human male was found frozen in a glacier pool in the Italian Alps in north west Italy, and is now carefully preserved in the South Tyrol Museum of Archaeology, in Bolzano, Italy. The bodily tissues of the 5,300 year old male (colloquially referred to as the Iceman or Ötzi) were well preserved despite damage related to freezing, and glacial movement. Associated articles of well-preserved clothing, tools, weapons and other devices were also present and have been studied in detail. Clinical examination and imaging investigations have also shown that the Icemen had experienced possible illnesses in his lifetime and had identifiable areas of arthritis and musculoskeletal injury. This report includes some key observations on the musculoskeletal state of Ötzi and reference to the involvement of tattoo markings. Some aspects about the aetiology of his abnormalities and inflammatory arthritis are considered along with possible treatments that he might have employed. METHODS AND RESULTS: We (WFK and MK) undertook a clinical musculoskeletal examination of the Iceman, details of which with available photographs and radiographic imaging pertaining to the musculoskeletal findings of the Iceman are reported here. The skin of the Iceman has numerous linear carbon tattoos, which are not of a decorative type. These have been presumed to possibly be "medicinal" tattoos administered for therapeutic reasons and may have been used in acupuncture-like treatment of pain. Spinal imaging identified areas of spinal damage and our observations have provided clues as to possible sites of spinal initiated pain and hence sites for administration of the "medicinal" tattoos. We observed body areas of the Iceman, in which imaging demonstrated arthritis and other forms of long-term musculoskeletal damage, but which do not have adjacent or corresponding "medicinal" tattoos. We contend that the back and leg "medicinal" tattoos correspond directly to sites of chronic right knee and right ankle pain, and left thoracolumbar pain. They also correspond to lower lumbar and sciatic referred radicular pain which may have a contributory cause related to the presence of a transitional lumbar 5 vertebra. Using recent published data (Keller et al. in Nature Commun 3:698, 2012. doi: 10.1038/ncomms1701 ) of the genome structure of the Iceman, we suggest some potential causes of the osteoarthritis or inflammatory joint injury may relate to presence of coronary heart disease (CHD) and Lyme disease (Borrelia burgdorferi) infection. We speculate on possible medical applications of natural products for self-medication. CONCLUSIONS: These observations highlight several diagnostic features of musculoskeletal conditions in the Iceman with the possibility that tattoos may have been used for diagnosis or location of his painful states. The origins of his musculoskeletal conditions are unclear but there are indications that Lyme disease and CHD may have been factors. The associations or use of natural products may give insights into their applications at the time of the life of the Iceman.</p

Modeling and structural analysis of PA clan serine proteases

<p>Abstract</p> <p>Background</p> <p>Serine proteases account for over a third of all known proteolytic enzymes; they are involved in a variety of physiological processes and are classified into clans sharing structural homology. The PA clan of endopeptidases is the most abundant and over two thirds of this clan is comprised of the S1 family of serine proteases, which bear the archetypal trypsin fold and have a catalytic triad in the order Histidine, Aspartate, Serine. These proteases have been studied in depth and many three dimensional structures have been experimentally determined. However, these structures mostly consist of bacterial and animal proteases, with a small number of plant and fungal proteases and as yet no structures have been determined for protozoa or archaea. The core structure and active site geometry of these proteases is of interest for many applications. This study investigated the structural properties of different S1 family serine proteases from a diverse range of taxa using molecular modeling techniques.</p> <p>Results</p> <p>Our predicted models from protozoa, archaea, fungi and plants were combined with the experimentally determined structures of 16 S1 family members and used for analysis of the catalytic core. Amino acid sequences were submitted to SWISS-MODEL for homology-based structure prediction or the LOOPP server for threading-based structure prediction. Predicted models were refined using INSIGHT II and SCRWL and validated against experimental structures. Investigation of secondary structures and electrostatic surface potential was performed using MOLMOL. The structural geometry of the catalytic core shows clear deviations between taxa, but the relative positions of the catalytic triad residues were conserved. Some highly conserved residues potentially contributing to the stability of the structural core were identified. Evolutionary divergence was also exhibited by large variation in secondary structure features outside the core, differences in overall amino acid distribution, and unique surface electrostatic potential patterns between species.</p> <p>Conclusions</p> <p>Encompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on S1 family serine proteases. Focusing on the common core containing the catalytic site of the enzyme, this analysis is beneficial for future molecular modeling strategies and structural analysis of serine protease models.</p

Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor

Asthma is a chronic airway disease characterized by inflammation, mucus hypersecretion and abnormal airway smooth muscle (ASM) contraction. Bacterial permeability family member A1, BPIFA1, is a secreted innate defence protein. Here we show that BPIFA1 levels are reduced in sputum samples from asthmatic patients and that BPIFA1 is secreted basolaterally from healthy, but not asthmatic human bronchial epithelial cultures (HBECs), where it suppresses ASM contractility by binding to and inhibiting the Ca(2+) influx channel Orai1. We have localized this effect to a specific, C-terminal α-helical region of BPIFA1. Furthermore, tracheas from Bpifa1(−/−) mice are hypercontractile, and this phenotype is reversed by the addition of recombinant BPIFA1. Our data suggest that BPIFA1 deficiency in asthmatic airways promotes Orai1 hyperactivity, increased ASM contraction and airway hyperresponsiveness. Strategies that target Orai1 or the BPIFA1 deficiency in asthma may lead to novel therapies to treat this disease