Synovial membrane protein expression differs between juvenile idiopathic arthritis subtypes in early disease

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1,000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at the level of the synovial membrane is required if we want to begin to understand the disease at the molecular and biochemical level. The synovial membrane proteome from early disease-stage, treatment naive JIA patients was compared between polyarticular and oligoarticular subgroups. Methods: Protein was extracted from 15 newly diagnosed, treatment naive JIA synovial membrane biopsies and separated by two dimensional fluorescent difference in-gel electrophoresis. Proteins displaying a two-fold or greater change in expression levels between the two subgroups were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry with expression further verified by Western blotting and immunohistochemistry. Results: Analysis of variance analysis (P ≤ 0.05) revealed 25 protein spots with a two-fold or greater difference in expression levels between polyarticular and oligoarticular patients. Hierarchical cluster analysis with Pearson ranked correlation revealed two distinctive clusters of proteins. Some of the proteins that were differentially expressed included: integrin alpha 2b (P = 0.04); fibrinogen D fragment (P = 0.005); collagen type VI (P = 0.03); fibrinogen gamma chain (P = 0.05) and peroxiredoxin 2 (P = 0.02). The identified proteins are involved in a number of different processes including platelet activation and the coagulation system. Conclusions: The data indicate distinct synovial membrane proteome profiles between JIA subgroups at an early stage in the disease process. The identified proteins also provide insight into differentially perturbed pathways which could influence pathological events at the joint level

Historical Pathways for Opioid Addiction, Withdrawal with Traditional and Alternative Treatment Options with Ketamine, Cannabinoids, and Noribogaine: A Narrative Review

Even as prescription opioid dispensing rates have begun to decrease, the use of illicit opioids such as heroin and fentanyl has increased. Thus, the end of the opioid epidemic is not in sight, and treating patients that are addicted to opioids remains of utmost importance. Currently, the primary pharmacotherapies used to treat opioid addiction over the long term are the opioid antagonist naltrexone, the partial-agonist buprenorphine, and the full agonist methadone. Naloxone is an antagonist used to rapidly reverse opioid overdose. While these treatments are well-established and used regularly, the gravity of the opioid epidemic necessitates that all possible avenues of treatment be explored. Therefore, in this narrative review, we analyze current literature regarding use of the alternative medications ketamine, noribogaine, and cannabinoids in treating patients suffering from opioid use disorder. Beyond its use as an anesthetic, ketamine has been shown to have many applications in several medical specialties. Of particular interest to the subject at hand, ketamine is promising in treating individuals addicted to opioids, alcohol, and cocaine. Therapeutically administered cannabinoids have been proposed for the treatment of multiple illnesses. These include, but are not limited to epilepsy, Parkinson\u27s disease, multiple sclerosis, chronic pain conditions, anxiety disorders, and addiction. The cannabinoid dronabinol has been seen to have varying effects. High doses appear to reduce withdrawal symptoms but this comes at the expense of increased adverse side effects such as sedation and tachycardia. Noribogaine is a weak MOR antagonist and relatively potent KOR agonist, which may explain the clinical anti-addictive effects. More research should be done to assess the viability of these medications for the treatment of OUD and withdrawal

The antenatal causes of cerebral palsy - Genetic and viral associations

Cerebral palsy is the most common neurological disorder in children. Epidemiological evidence suggests that antenatal origins are a major cause. Currently there is no antenatal test for cerebral palsy, no proven preventable measures in late pregnancy, and no known cure. Cerebral palsy affects not only the diagnosed child, but also their family and the community, requiring considerable social and financial resources to assist these children in their daily lives.Catherine S. Gibson, Alastair H. MacLennan, Paul N. Goldwater, and Gustaaf A. Dekker for The South Australian Cerebral Palsy Research Grou

Excavation of a neolithic house at Yarnbury, near Grassington, North Yorkshire

YesLandscape geophysical survey around the small upland ‘henge’ at Yarnbury, Grassington, North Yorkshire revealed few anthropogenic features around the enclosure but did identify a small rectangular structure in the same field. Sample trenching of this feature, radiocarbon and archaeomagnetic dating proved it to be an earlier Neolithic post and wattle structure of a type that is being increasingly recognised in Ireland and the west of Britain. It is the first to be recognised in the Yorkshire Dales and it is argued that the Dales may have been pivotal in the Neolithic for east–west trade as well as pastoral upland agriculture

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm

A Systematic Review of Music Therapy Practice and Outcomes with Acute Adult Psychiatric In-Patients

PMCID: PMC3732280This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Deactivation of a single-site gold-on-carbon acetylene hydrochlorination catalyst: An X-ray absorption and inelastic neutron scattering study

Single-site Au species supported on carbon have been shown to be the active sites for acetylene hydrochlorination. The evolution of these single-site species has been monitored by Au L3 X-ray Absorption Spectroscopy (XAS). Alternating between a standard reaction mixture of HCl/C2H2 and the single reactants, has provided insights into the reaction mechanism and catalyst deactivation processes. We demonstrate that oxidative addition of HCl across an Au(I) chloride species requires concerted addition with C2H2, in accordance with both the XAS measurements of Au oxidation state and the reaction kinetics being 1st order with respect to each reactant. The addition of excess C2H2 changes the Au speciation and results in the formation of oligomeric acetylene species which were detected by inelastic neutron scattering. Catalyst deactivation at extended reaction times can be correlated with the formation of metallic Au particles. The presence of this Au(0) species generated during the sequential gas experiments or after prolonged reaction times, results in the analysis of the normalised near edge white line intensity of the Au L3 X-ray absorption spectrum alone becoming an unsuitable guide for identifying the active Au species, affecting the strong correlation between normalized white line height and VCM productivity usually observed in the active catalyst. Thus, a combination of scanning transmission electron microscopy and detailed modelling of whole XAS spectrum was required to distinguish active Au(I) and Au(III) species from the spectator Au(0) component

Mobile health applications for managing atrial fibrillation for healthcare professionals and patients: a systematic review

Aims A plethora of mobile health applications (m-health apps) to support healthcare are available for both patients and healthcare professionals (HCPs) but content and quality vary considerably and few have undergone formal assessment. The aim is to systematically review the literature on m-health apps for managing atrial fibrillation (AF) that examine the impact on knowledge of AF, patient and HCP behaviour, patients’ quality-of-life, and user engagement. Methods and results MEDLINE, EMBASE, CINAHL, and PsychInfo were searched from 1 January 2005 to 5 September 2019, with hand-searching of clinical trial registers and grey literature. Studies were eligible for inclusion if they reported changes in any of the following: (i) knowledge of AF; (ii) provider behaviour (e.g. guideline adherence); (iii) patient behaviour (e.g. medication adherence); (iv) patient quality-of-life; and (v) user engagement. Two reviewers independently assessed articles for eligibility. A narrative review was undertaken as included studies varied widely in their design, interventions, comparators, and outcomes. Seven studies were included; six m-health apps aimed at patients and one at HCPs. Mobile health apps ranged widely in design, features, and method of delivery. Four studies reported patient knowledge of AF; three demonstrated significant knowledge improvement post-intervention or compared to usual care. One study reported greater HCP adherence to oral anticoagulation guidelines after m-health app implementation. Two studies reported on patient medication adherence and quality-of-life; both showed improved quality-of-life post-intervention but only one observed increased adherence. Regarding user engagement, five studies reported patient perspectives on usability, three on acceptability, and one on feasibility; overall all m-health apps were rated positively. Conclusion Mobile health apps demonstrate improvements in patient knowledge, behaviour, and quality of life. Studies formally evaluating the impact of m-health on HCP behaviour are scarce and larger-scale studies with representative patient cohorts, appropriate comparators, and longer-term assessment of the impact of m-health apps are warranted

Hubble Space Telescope hot Jupiter transmission spectral survey: a detection of Na and strong optical absorption in HAT-P-1b

We present an optical to near-infrared transmission spectrum of the hot Jupiter HAT-P-1b, based on Hubble Space Telescope observations, covering the spectral regime from 0.29 to 1.027 μm with Space Telescope Imaging Spectrograph (STIS), which is coupled with a recent Wide Field Camera 3 (WFC3) transit (1.087 to 1.687 μm). We derive refined physical parameters of the HAT-P-1 system, including an improved orbital ephemeris. The transmission spectrum shows a strong absorption signature shortward of 0.55 μm, with a strong blueward slope into the near-ultraviolet. We detect atmospheric sodium absorption at a 3.3σ significance level, but find no evidence for the potassium feature. The red data imply a marginally flat spectrum with a tentative absorption enhancement at wavelength longer than ∼ 0.85 μm. The STIS and WFC3 spectra differ significantly in absolute radius level (4.3 ± 1.6 pressure scaleheights), implying strong optical absorption in the atmosphere of HAT-P-1b. The optical to near-infrared difference cannot be explained by stellar activity, as simultaneous stellar activity monitoring of the G0V HAT-P-1b host star and its identical companion show no significant activity that could explain the result. We compare the complete STIS and WFC3 transmission spectrum with theoretical atmospheric models which include haze, sodium and an extra optical absorber. We find that both an optical absorber and a supersolar sodium to water abundance ratio might be a scenario explaining the HAT-P-1b observations. Our results suggest that strong optical absorbers may be a dominant atmospheric feature in some hot Jupiter exoplanets