Growing awareness of the multiplicity of roles for the IL-1 family in immune regulation has prompted research exploring these cytokines in the context of vaccine-induced immunity. While tightly regulated, cytokines of the IL-1 family are normally released in response to cellular stress and in combination with other danger/damage associated molecular patterns (DAMPs), triggering potent local and systemic immune responses. In the context of infection or autoimmunity, engagement of IL-1 family receptors links robust innate responses to adaptive immunity. Clinical and experimental evidence has revealed that many approved adjuvants induce the release of one or multiple IL-1 family cytokines. The coordinated release of IL-1 family members in response to adjuvant-induced damage or cell death may be a determining factor in the transition from local inflammation to the induction of an adaptive response. Here, we analyse the effects of IL-1 family cytokines on innate and adaptive immunity with a particular emphasis on activation of antigen presenting cells and induction of T cell-mediated immunity, and we address in detail the contribution of these cytokines to the modes of action of vaccine adjuvants including those currently approved for human use. This article is protected by copyright. All rights reserved.
Influenza virus infection is now recognised as a risk factor for invasive pulmonary aspergillosis (IPA). Delays in diagnosis contribute to delayed commencement of antifungal therapy. Additionally, the emergence of resistance to first-line triazole antifungal agents puts emphasis on early detection to prevent adverse outcomes. We present 2 allogeneic stem cell transplant patients who developed IPA due to triazole-resistant Aspergillus fumigatus following influenza infection. We underline the challenges faced in the management of these cases, the importance of early diagnosis and need for surveillance given the emergence of triazole-resistance. This article is protected by copyright. All rights reserved.
The use of graphene-based nanocomposites as electromechanical sensors has been broadly explored in recent times with a number of papers describing porous, foam-like composites. However, there are no reported foam-based materials that are capable of large dynamic compressive load measurements and very few studies on composite impact sensing. In this work, we describe a simple method of infusing commercially-available foams with pristine graphene to form conductive composites, which we refer to as G-foam. Displaying a strain-dependent electrical response, G-foam was found to be a reasonably effective pressure sensing material. More interestingly, G-foam is a sensitive impact-sensing material. Through the addition of various amounts of polymer filler, the mechanical properties of the composites can be tuned leading to the controllable variation of the impact sensing range. We have developed a simple model which quantitatively explains all our impact sensing data.
Pulmonary arterial hypertension (PAH) is a devastating disease and treatment options are limited. Urocortin-2 (Ucn-2) has shown promising therapeutic effects in experimental and clinical left ventricular heart failure (HF). Our aim was to analyze the expression of Ucn-2 in human and experimental PAH, and to investigate the effects of human Ucn-2 (hUcn-2) administration in rats with monocrotaline (MCT)-induced pulmonary hypertension (PH). Tissue samples were collected from patients with and without PAH and from rats with MCT-induced PH; and hUcn-2 (5ug/kg, bi-daily, i.p., for 10 days) or vehicle was administered to male wistar rats subjected to MCT injection or pulmonary artery banding (PAB) to induce right ventricular (RV) overload without PAH. Expression of Ucn-2 and its receptor was increased in the RV of patients and rats with PAH. hUcn-2 treatment reduced PAH in MCT-rats, resulting in decreased morbidity, improved exercise capacity and attenuated pulmonary arterial and RV remodeling and dysfunction. Additionally, RV gene expression of hypertrophy and failure signaling pathways were attenuated. hUcn-2 treatment also attenuated PAB-induced RV hypertrophy. Ucn-2 levels are altered in human and experimental PAH. hUcn-2 treatment attenuates PAH and RV dysfunction in MCT-induced PH, has direct anti-remodeling effects on the pressure-overloaded RV, and improves pulmonary vascular function.
The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non-alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug-drug interaction tables have been updated and new tables are included. Treatment options for direct-acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three-drug combination may be as effective as a five-drug regimen, and may reduce treatment duration from 18-24 to 6-10 months. Version 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages.
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This study describes the prevalence, incidence density, severity, and nature of injuries in elite field hockey players over the Dutch 2015-2016 season. Eighty players answered a baseline questionnaire and were subsequently followed up every 2 weeks to report the hours spent on training/competition and experienced injuries, which were registered using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. Of the 74 players included in the analysis, 52 (70%) reported 112 injuries. Eighty-seven injuries (78%) received medical attention, and 56 (50%) led to training/competition time-loss. Thirty-four injuries (30%) hampered players' availability to train and compete. Most of the injuries (74%) were not caused by any contact. The mean prevalence of injury was 29% (95% confidence interval [CI] 3-55) for all, 9% (95% CI 0-20) for acute, and 14% (95% CI 0-36) for overuse injuries. Players sustained 3.5 (95% CI 2.5-4.5) new acute injuries per 1000 hours of training and 12.3 (95% CI 7.6-17.0) per 1000 hours of competition. The median of the severity score was 28 from 100 (25%-75% interquartile range [IQR] 16-42) for all, 35 (IQR 23-53) for acute, and 21 (IQR 16-31) for overuse injuries. On average, 1 in 4 elite field hockey players experiences an injury within a 2-week period during the season. Although acute injuries are common, overuse injuries pose a comparable problem in elite field hockey. As injuries are a burden on players' health and may hamper performance and availability to train and compete, prevention is of great importance.
Community health workers deployed around South Africa's primary health care clinics, supply indispensable support for the world's largest HIV/AIDS treatment programme. Interviews with these workers illuminated the contribution they make to anti-retroviral treatment (ART) of HIV/AIDS patients and the motivations that sustain their engagement. Their testimony highlights points of stress in the programme and supplies insights into the quality of its implementation. Finally, the paper addresses issues about the sustainability of a programme that depends on a group of workers who are not yet fully incorporated into the public sector.