Changing pattern of visceral leishmaniasis, United Kingdom, 1985-2004.

A 20-year (1985-2004) retrospective review of 39 patients with imported visceral leishmaniasis found that tourism to Mediterranean countries and HIV infection were associated with visceral leishmaniasis. Diagnosis was often delayed. Treatment with liposomal amphotericin B has improved prognosis. Visceral leishmaniasis should be made a reportable disease

A Randomized Controlled Double Blind Trial of Ciclosporin versus Prednisolone in the Management of Leprosy Patients with New Type 1 Reaction, in Ethiopia.

BACKGROUND: Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life. RESULTS: Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36. CONCLUSIONS: This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed

Mindfulness-based interventions in epilepsy: a systematic review

Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined

Intramuscular myxoid lipoma in the proximal forearm presenting as an olecranon mass with superficial radial nerve palsy: a case report

<p>Abstract</p> <p>Background</p> <p>Extremity lipomas may occur in any location, including the proximal forearm. We describe a case of a patient with an intramuscular lipoma presenting as an unusual posterior elbow mass.</p> <p>Case presentation</p> <p>We discuss the case of a 57-year-old Caucasian man who presented with a tender, posterior elbow mass initially diagnosed as chronic olecranon bursitis. A minor sensory disturbance in the distribution of the superficial radial nerve was initially thought to be unrelated, but was likely caused by mass effect from the lipoma. No pre-operative advanced imaging was obtained because the diagnosis was felt to have already been made. At the time of surgery, a fatty mass originating in the volar forearm muscles was found to have breached the dorsal forearm fascia and displaced the olecranon bursa. Tissue diagnosis was made by histopathology as a myxoid lipoma with no aggressive features. Post-operative recovery was uneventful.</p> <p>Conclusion</p> <p>We present a case of an unusual elbow mass presenting with symptoms consistent with chronic olecranon bursitis, a relatively common condition. The only unexplained pre-operative finding was the non-specific finding of a transient superficial radial nerve deficit. We remind clinicians to be cautious when diagnosing soft tissue masses in the extremities when unexplained physical findings are present.</p

Accessibility-based reranking in multimedia search engines

Traditional multimedia search engines retrieve results based mostly on the query submitted by the user, or using a log of previous searches to provide personalized results, while not considering the accessibility of the results for users with vision or other types of impairments. In this paper, a novel approach is presented which incorporates the accessibility of images for users with various vision impairments, such as color blindness, cataract and glaucoma, in order to rerank the results of an image search engine. The accessibility of individual images is measured through the use of vision simulation filters. Multi-objective optimization techniques utilizing the image accessibility scores are used to handle users with multiple vision impairments, while the impairment profile of a specific user is used to select one from the Pareto-optimal solutions. The proposed approach has been tested with two image datasets, using both simulated and real impaired users, and the results verify its applicability. Although the proposed method has been used for vision accessibility-based reranking, it can also be extended for other types of personalization context

A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii.

Two-pore channels (TPCs) are a ubiquitous family of cation channels that localize to acidic organelles in animals and plants to regulate numerous Ca2+-dependent events. Little is known about TPCs in unicellular organisms despite their ancient origins. Here, we characterize a TPC from Toxoplasma gondii, the causative agent of toxoplasmosis. TgTPC is a member of a novel clad of TPCs in Apicomplexa, distinct from previously identified TPCs and only present in coccidians. We show that TgTPC localizes not to acidic organelles but to the apicoplast, a non-photosynthetic plastid found in most apicomplexan parasites. Conditional silencing of TgTPC resulted in progressive loss of apicoplast integrity, severely affecting growth and the lytic cycle. Isolation of TPC null mutants revealed a selective role for TPCs in replication independent of apicoplast loss that required conserved residues within the pore-lining region. Using a genetically-encoded Ca2+ indicator targeted to the apicoplast, we show that Ca2+ signals deriving from the ER but not from the extracellular space are selectively transmitted to the lumen. Deletion of the TgTPC gene caused reduced apicoplast Ca2+ uptake and membrane contact site formation between the apicoplast and the ER. Fundamental roles for TPCs in maintaining organelle integrity, inter-organelle communication and growth emerge

Boron-Based Inhibitors of the NLRP3 Inflammasome.

NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy diphenylborinate (2APB). Unfortunately, in addition to inhibiting NLRP3, 2APB also displays non-selective effects on cellular Ca2+ homeostasis. Here, we use 2APB as a chemical scaffold to build a series of inhibitors, the NBC series, which inhibit the NLRP3 inflammasome in vitro and in vivo without affecting Ca2+ homeostasis. The core chemical insight of this work is that the oxazaborine ring is a critical feature of the NBC series, and the main biological insight the use of NBC inhibitors led to was that NLRP3 inflammasome activation was independent of Ca2+. The NBC compounds represent useful tools to dissect NLRP3 function, and may lead to oxazaborine ring-containing therapeutics

Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistanc

This is the final version of the article. Available from NIEHS via the DOI in this record.Open access journalBACKGROUND: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. OBJECTIVE: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. METHODS: The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. DISCUSSION: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental "hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways. CONCLUSIONS: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.This manuscript was conceived at a workshop (Antimicrobial Resistance in the Environment: Assessing and Managing Effects of Anthropogenic Activities) held 4–8 March 2012 in Montebello, Québec, Canada. The workshop was sponsored by the Canadian Society of Microbiologists, with financial support from AstraZeneca Ltd.; Pfizer Animal Health; F. Hoffman-La Roche Ltd.; GlaxoSmithKline; Unilever; Huvepharma; the American Cleaning Institute; the Canadian Animal Health Institute; the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety; Health Canada; and the Public Health Agency of Canada

Framing Male Circumcision to Promote its Adoption in Different Settings

The effectiveness of male circumcision in preventing transmission of HIV from females to males has been established. Those who are now advocating its widespread use face many challenges in convincing policy-makers and the public of circumcision’s value. We suggest that frames are a useful lens for communicating public health messages that may help promote adoption of circumcision. Frames relate to how individuals and societies perceive and understand the world. Existing frames are often hard to shift, and should be borne in mind by advocates and program implementers as they attempt to promote male circumcision by invoking new frames. Frames differ across and within societies, and advocates must find ways of delivering resonant messages that take into account prior perceptions and use the most appropriate means of communicating the benefits and value of male circumcision to different audiences

Bacterial microevolution and the Pangenome

The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history