The first small-molecule inhibitors of members of the ribonuclease E family

The Escherichia coli endoribonuclease RNase E is central to the processing and degradation of all types of RNA and as such is a pleotropic regulator of gene expression. It is essential for growth and was one of the first examples of an endonuclease that can recognise the 5′-monophosphorylated ends of RNA thereby increasing the efficiency of many cleavages. Homologues of RNase E can be found in many bacterial families including important pathogens, but no homologues have been identified in humans or animals. RNase E represents a potential target for the development of new antibiotics to combat the growing number of bacteria that are resistant to antibiotics in use currently. Potent small molecule inhibitors that bind the active site of essential enzymes are proving to be a source of potential drug leads and tools to dissect function through chemical genetics. Here we report the use of virtual high-throughput screening to obtain small molecules predicted to bind at sites in the N-terminal catalytic half of RNase E. We show that these compounds are able to bind with specificity and inhibit catalysis of Escherichia coli and Mycobacterium tuberculosis RNase E and also inhibit the activity of RNase G, a paralogue of RNase E

Revision total hip arthroplasty using the Zweymuller femoral stem

Background: A variety of femoral stem designs have been reported to be successful in revision total hip arthroplasty without consensus as to optimal design. We evaluated the clinical and radiographic outcomes in a consecutive series of femoral revisions using a wedge-shape, tapered-stem design at medium and long-term follow-up. Materials and methods: We performed a retrospective review of clinical and radiographic outcomes of twenty-eight consecutive femoral revisions arthroplasties, which were done using the Zweymuller femoral stem. Results: The mean follow-up was 7.4 years (range 2-15 years). No stem re-revision was necessary. All stems were judged to be stable by radiographic criteria at the most recent follow-up. The final mean Harris hip score was 90. There was no difference in Harris hip scores, implant stability, or radiological appearance (distal cortical hypertrophy or proximal stress shielding) of the implants between medium-term (mean 5.7 years) and long-term (mean 12.4 years) follow-up. Conclusions: We found the Zweymuller femoral stem design to be durable for revision hip arthroplasty when there is an intact metaphyseal-diaphyseal junction for adequate press-fit stability at surgery. © Springer-Verlag 2008

2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral Pain Research Retreat, Manchester. Part 1: Terminology, definitions, clinical examination, natural history, patellofemoral osteoarthritis and patient-reported outcome measures

Patellofemoral pain (PFP) typically presents as diffuse anterior knee pain, usually with activities such as squatting, running, stair ascent and descent. It is common in active individuals across the lifespan,1–4 and is a frequent cause for presentation at physiotherapy, general practice, orthopaedic and sports medicine clinics in particular.5 ,6 Its impact is profound, often reducing the ability of those with PFP to perform sporting, physical activity and work-related activities pain-free. Increasing evidence suggests that it is a recalcitrant condition, persisting for many years.7–9 In an attempt to share recent innovations, build on the first three successful biennial retreats and define the ‘state of the art’ for this common, impactful condition; the 4th International Patellofemoral Pain Research Retreat was convened. The 4th International Patellofemoral Research Retreat was held in Manchester, UK, over 3 days (September 2–4th, 2015). After undergoing peer-review for scientific merit and relevance to the retreat, 67 abstracts were accepted for the retreat (50 podium presentations, and 17 short presentations). The podium and short presentations were grouped into five categories; (1) PFP, (2) factors that influence PFP (3) the trunk and lower extremity (4) interventions and (5) systematic analyses. Three keynote speakers were chosen for their scientific contribution in the area of PFP. Professor Andrew Amis spoke on the biomechanics of the patellofemoral joint. Professor David Felson spoke on patellofemoral arthritis,10 and Dr Michael Ratleff's keynote theme was PFP in the adolescent patient.11 As part of the retreat, we held structured, whole-group discussions in order to develop consensus relating to the work presented at the meeting as well as evidence gathered from the literature

The origins of belonging : Social motivation in infants and young children

Our reliance on our group members has exerted a profound influence over our motivation: successful group functioning requires that we are motivated to interact, and engage, with those around us. In other words, we need to belong. In this article, I explore the developmental origins of our need to belong. I discuss existing evidence that, from early in development, children seek to affiliate with others and to form long-lasting bonds with their group members. Furthermore, when children are deprived of a sense of belonging, it has negative consequences for their well-being. This focus on social motivation enables us to examine why and in what circumstances children engage in particular behaviours. It thus provides an important complement to research on social cognition. In doing so, it opens up important questions for future research and provides a much-needed bridge between developmental and social psychology

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

2018 Consensus statement on exercise therapy and physical interventions (orthoses, taping and manual therapy) to treat patellofemoral pain: Recommendations from the 5th International Patellofemoral Pain Research Retreat, Gold Coast, Australia, 2017

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. Patellofemoral pain affects a large proportion of the population, from adolescents to older adults, and carries a substantial personal and societal burden. An international group of scientists and clinicians meets biennially at the International Patellofemoral Research Retreat to share research findings related to patellofemoral pain conditions and develop consensus statements using best practice methods. This consensus statement, from the 5th International Patellofemoral Research Retreat held in Australia in July 2017, focuses on exercise therapy and physical interventions (eg, orthoses, taping and manual therapy) for patellofemoral pain. Literature searches were conducted to identify new systematic reviews and randomised controlled trials (RCTs) published since the 2016 Consensus Statement. The methodological quality of included systematic reviews and RCTs was graded using AMSTAR and PEDro, respectively. Evidence-based statements were developed from included papers and presented to a panel of 41 patellofemoral pain experts for consensus discussion and voting. Recommendations from the expert panel support the use of exercise therapy (especially the combination of hip-focused and knee-focused exercises), combined interventions and foot orthoses to improve pain and/or function in people with patellofemoral pain. The use of patellofemoral, knee or lumbar mobilisations in isolation, or electrophysical agents, is not recommended. There is uncertainty regarding the use of patellar taping/bracing, acupuncture/dry needling, manual soft tissue techniques, blood flow restriction training and gait retraining in patients with patellofemoral pain. In 2017, we launched the International Patellofemoral Research Network (www.ipfrn.org) to consolidate and grow our patellofemoral research community, facilitate collaboration and disseminate patellofemoral pain knowledge to clinicians and the general public. The 6th International Patellofemoral Research Retreat will be held in Milwaukee, Wisconsin, USA, in October 2019

Pandemic Influenza A H1N1 2009 Infection versus Vaccination: A Cohort Study Comparing Immune Responses in Pregnancy

Background: With the emergence of H1N1 pandemic (pH1N1) influenza, the CDC recommended that pregnant women be one of five initial target groups to receive the 2009 monovalent H1N1 vaccine, regardless of prior infection with this influenza strain. We sought to compare the immune response of pregnant women to H1N1 infection versus vaccination and to determine the extent of passive immunity conferred to the newborn. Methods/Findings: During the 2009-2010 influenza season, we enrolled a cohort of women who either had confirmed pH1N1 infection during pregnancy, did not have pH1N1 during pregnancy but were vaccinated against pH1N1, or did not have illness or vaccination. Maternal and umbilical cord venous blood samples were collected at delivery. Hemagglutination inhibition assays (HAI) for pH1N1 were performed. Data were analyzed using linear regression analyses. HAIs were performed for matched maternal/cord blood pairs for 16 women with confirmed pH1N1 infection, 14 women vaccinated against pH1N1, and 10 women without infection or vaccination. We found that pH1N1 vaccination and wild-type infection during pregnancy did not differ with respect to (1) HAI titers at delivery, (2) HAI antibody decay slopes over time, and (3) HAI titers in the cord blood. Conclusions: Vaccination against pH1N1 confers a similar HAI antibody response as compared to pH1N1 infection durin

Analysis of two methods of isometric muscle contractions during the anti-G straining maneuver

This study investigated the difference in Mean Arterial Pressure (MAP) and Cardiac Output (CO) between two methods of isometric muscle contractions during the Anti-G Straining Maneuver (AGSM). 12 subjects (ages 18 to 38 yrs, height 176.8 +/- 7.4 cm, body mass 78.8 +/- 15.6 kg, percent body fat 14.3 +/- 6.6%) participated in the study. The study was a one-way within-subject design with test conditions counterbalanced. Two methods of isometric muscle contractions lasting 30 seconds each were assessed; an isometric push contraction and an isometric muscle tensing contraction. The dependent parameters were MAP and CO. The average MAP during the push contraction was 123 mmHg, SD +/- 11 and for tense was 118 mmHg, SD +/- 8. CO was 7.6 L/min, SD +/- 1.6 for push and 7.9 L/min, SD +/- 2.0 for tense method. Dependent t-tests revealed t(11) = 1.517, p = 0.157 for MAP and t(11) = 0.875, p = 0.400 for CO. This study demonstrated that the two methods of isometric muscle contractions were not statistically different with regards to MAP and CO. Therefore, both forms of isometric contractions may be potentially useful when performing the muscle contraction portion of the AGSM