Case report: intra-tendinous ganglion of the anterior cruciate ligament in a young footballer

A 20-year-old male medical student and keen rugby player presented with a 12-month history of progressively worsening right knee pain and stiffness with no history of trauma. Clinical examination revealed effusion and posterior knee pain exacerbated by end range movement and an extension lag of 15 degrees. Physiotherapy to improve the range of motion proved unsuccessful. Magnetic resonance imaging showed that the ACL was grossly thickened and displaced by material reported as mucoid in nature. There were also areas of focally high signal in relation to its tibial attachment and intra osseous small cysts. Arthroscopic examination revealed a ganglion related to the tibial attachment of the ACL and gross thickening and discoloration of the ACL. Biopsies were taken showing foci of mucoid degeneration in the ACL. A large intra-ACL mass of brownish coloured tissue was excised arthroscopically. Already at 2 weeks follow up the patient had greatly improved range of movement and was pain free. However, upon returning to rugby, joint instability was noticed and a tear of the ACL was confirmed. This rare clinical condition can be diagnosed with MRI and arthroscopic debridement effectively relieves symptoms. This case report illustrates that augmentation or reconstruction may end up being the definitive treatment for athletes. It may also offer some support to the argument that mucoid degeneration and ganglion cyst formation share a similar pathogenesis to intra-osseous cyst formation

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Measurement of quarkonium production in proton–lead and proton–proton collisions at 5.02 TeV with the ATLAS detector

The modification of the production of J/ψ, ψ(2S), and Υ(nS) (n=1,2,3) in p+Pb collisions with respect to their production in pp collisions has been studied. The p+Pb and pp datasets used in this paper correspond to integrated luminosities of 28 nb−1 and 25 pb−1 respectively, collected in 2013 and 2015 by the ATLAS detector at the LHC, both at a centre-of-mass energy per nucleon pair of 5.02 TeV. The quarkonium states are reconstructed in the dimuon decay channel. The yields of J/ψ and ψ(2S) are separated into prompt and non-prompt sources. The measured quarkonium differential cross sections are presented as a function of rapidity and transverse momentum, as is the nuclear modification factor, RpPb for J/ψ and Υ(nS). No significant modification of the J/ψ production is observed while Υ(nS) production is found to be suppressed at low transverse momentum in p+Pb collisions relative to pp collisions. The production of excited charmonium and bottomonium states is found to be suppressed relative to that of the ground states in central p+Pb collisions

Search for excited electrons singly produced in proton–proton collisions at \sqrt{s} = 13 TeV with the ALAS experiment at the LHC

A search for excited electrons produced in pp collisions at s√ = 13 TeV via a contact interaction qq¯→ee∗ is presented. The search uses 36.1 fb −1 of data collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider. Decays of the excited electron into an electron and a pair of quarks ( eqq¯ ) are targeted in final states with two electrons and two hadronic jets, and decays via a gauge interaction into a neutrino and a W boson ( νW ) are probed in final states with an electron, missing transverse momentum, and a large-radius jet consistent with a hadronically decaying W boson. No significant excess is observed over the expected backgrounds. Upper limits are calculated for the pp→ee∗→eeqq¯ and pp→ee∗→eνW production cross sections as a function of the excited electron mass me∗ at 95% confidence level. The limits are translated into lower bounds on the compositeness scale parameter Λ of the model as a function of me∗ . For me∗<0.5 TeV , the lower bound for Λ is 11 TeV . In the special case of me∗=Λ , the values of me∗<4.8 TeV are excluded. The presented limits on Λ are more stringent than those obtained in previous searches

Measurements of Higgs bosons decaying to bottom quarks from vector boson fusion production with the ATLAS experiment at √=13TeV

The paper presents a measurement of the Standard Model Higgs Boson decaying to b-quark pairs in the vector boson fusion (VBF) production mode. A sample corresponding to 126 fb−1 of s√=13TeV proton–proton collision data, collected with the ATLAS experiment at the Large Hadron Collider, is analyzed utilizing an adversarial neural network for event classification. The signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model for VBF Higgs production, is measured to be 0.95+0.38−0.36 , corresponding to an observed (expected) significance of 2.6 (2.8) standard deviations from the background only hypothesis. The results are additionally combined with an analysis of Higgs bosons decaying to b-quarks, produced via VBF in association with a photon