Reactive oxygen species and nitric oxide in viral diseases

Metabolites derived from superoxide (o2 •−) and nitric oxide (NO•) play an important role in antimicrobial and antitumoral defense, but may also harm the host. Low levels of such metabolites can also facilitate viral replication because of their mitogenic effects on cells. Most viruses grow better in proliferating cells, and indeed, many viruses induced in their host cell changes similar to those seen early after treatment with mitogenic lectins. Influenza and paramyxoviruses activate in phagocytes the generation of superoxide by a mechanism involving the interaction between the viral surface glycoproteins and the phagocyte's plasma membrane. Interestingly, viruses that activate this host defense mechanism are toxic when injected in the bloodstream of animals. Mice infected with influenza virus undergo oxidative stress. In addition, a wide array of cytokines are formed in the lung, contributing to the systemic effects of influenza. Oxidative stress is seen also in chronic viral infections, such as AIDS and viral hepatitis. Oxidant production in viral hepatitis may contribute to the emergence of hepatocellular carcinoma, a tumor seen in patients after years of chronic inflammation of the liver. Antioxidants and agents that downregulate proinflammatory cytokines and lipid mediators may be a useful complement to specific antiviral drugs in the therapy of viral disease

PrfA activation at the single cell level in Listeria monocytogenes

The human pathogen Listeria monocytogenes is able to transition from environmental saprophyte to facultative intracellular bacteria. In this process, virulence gene expression is controlled by the positive regulatory factor A (PrfA). Recent studies at the single cell level have shown that gene expression in response to stress exposure is stochastic in individual bacteria cells. Current studies applied those general findings to Listeria cells, revealing that PrfA as well is not regulated consistently, but that PrfA activity differs between individual cells. The aim of this study was to elucidate the mechanism by which Listeria regulates PrfA activation at the single cell level and whether this property is heritable or not. A reporter fusion, namely an eGFP sequence, integrated following the PrfA dependent promoter (Phly), was used to visualize the activation after heat stress exposure. Fluorescence activated cell sorting (FACS) was used to distinguish PrfA positive and negative cells. After passaging and sorting PrfA activating versus non-activating cells over several generations, two stable fluorescent phenotypes emerged. A comparison between the genome of the PrfA positive and its parent strain revealed a single-nucleotide polymorphism (SNP) in the CDS of LMRG_02823, as well as a mutation in the 5'UTR of LMRG_00195, both LPXTG family cell wall associated proteins regulated via small RNAs. The link between those mutations and PrfA activation is currently being investigated

A smartphone-based health care chatbot to promote self-management of chronic pain (SELMA) : pilot randomized controlled trial

Background: Ongoing pain is one of the most common diseases and has major physical, psychological, social, and economic impacts. A mobile health intervention utilizing a fully automated text-based health care chatbot (TBHC) may offer an innovative way not only to deliver coping strategies and psychoeducation for pain management but also to build a working alliance between a participant and the TBHC. Objective: The objectives of this study are twofold: (1) to describe the design and implementation to promote the chatbot painSELfMAnagement (SELMA), a 2-month smartphone-based cognitive behavior therapy (CBT) TBHC intervention for pain self-management in patients with ongoing or cyclic pain, and (2) to present findings from a pilot randomized controlled trial, in which effectiveness, influence of intention to change behavior, pain duration, working alliance, acceptance, and adherence were evaluated. Methods: Participants were recruited online and in collaboration with pain experts, and were randomized to interact with SELMA for 8 weeks either every day or every other day concerning CBT-based pain management (n=59), or weekly concerning content not related to pain management (n=43). Pain-related impairment (primary outcome), general well-being, pain intensity, and the bond scale of working alliance were measured at baseline and postintervention. Intention to change behavior and pain duration were measured at baseline only, and acceptance postintervention was assessed via self-reporting instruments. Adherence was assessed via usage data. Results: From May 2018 to August 2018, 311 adults downloaded the SELMA app, 102 of whom consented to participate and met the inclusion criteria. The average age of the women (88/102, 86.4%) and men (14/102, 13.6%) participating was 43.7 (SD 12.7) years. Baseline group comparison did not differ with respect to any demographic or clinical variable. The intervention group reported no significant change in pain-related impairment (P=.68) compared to the control group postintervention. The intention to change behavior was positively related to pain-related impairment (P=.01) and pain intensity (P=.01). Working alliance with the TBHC SELMA was comparable to that obtained in guided internet therapies with human coaches. Participants enjoyed using the app, perceiving it as useful and easy to use. Participants of the intervention group replied with an average answer ratio of 0.71 (SD 0.20) to 200 (SD 58.45) conversations initiated by SELMA. Participants’ comments revealed an appreciation of the empathic and responsible interaction with the TBHC SELMA. A main criticism was that there was no option to enter free text for the patients’ own comments. Conclusions: SELMA is feasible, as revealed mainly by positive feedback and valuable suggestions for future revisions. For example, the participants’ intention to change behavior or a more homogenous sample (eg, with a specific type of chronic pain) should be considered in further tailoring of SELMA

Quality assurance in transnational higher education : a case study of the tropEd network

Transnational or cross-border higher education has rapidly expanded since the 1980s. Together with that expansion issues on quality assurance came to the forefront. This article aims to identify key issues regarding quality assurance of transnational higher education and discusses the quality assurance of the tropEd Network for International Health in Higher Education in relation to these key issues.; Literature review and review of documents.; From the literature the following key issues regarding transnational quality assurance were identified and explored: comparability of quality assurance frameworks, true collaboration versus erosion of national education sovereignty, accreditation agencies and transparency. The tropEd network developed a transnational quality assurance framework for the network. The network accredits modules through a rigorous process which has been accepted by major stakeholders. This process was a participatory learning process and at the same time the process worked positive for the relations between the institutions.; The development of the quality assurance framework and the process provides a potential example for others

Documentation and interpretation of the petroglyphs of Chichictara, Palpa (Peru), using terrestrial laser scanning and image-based 3D modeling

In Chichictara, southern Peru, petroglyphs cover the surface of around 150 rocks, located in a small valley. The goals of the Chichictara Project are the documentation of the petroglyphs, the dating of them and an understanding of the original social function of the site and its components. The presented research methodology is determined by two properties of petroglyphs: Firstly, they are an artificial intervention into the natural environment. That means their natural and archaeological environment must be decisively included into the interpretation. Secondly, their iconographic value is very high, which means that similarities with other archaeological findings have to be made evident. Thus, the site of Chichictara was documented in 3D by means of laser scanning and photogrammetry. The results will be included into a 3D model of the entire Palpa region and connected with a GIS database containing spatial and archaeological information – the rocks will tell us about the past

Preparedness of Anesthesiologists Working in Humanitarian Disasters

Abstract Objective Many skills needed to provide patients with safe, timely, and adequate anesthesia care during humanitarian crisis and disaster relief operations are not part of the daily routine before deployment. An exploratory study was conducted to identify preparedness, knowledge, and skills needed for deployment to complex emergencies. Methods Anesthesiologists who had been deployed during humanitarian crisis and disaster relief operations completed an online questionnaire assessing their preparedness, skills, and knowledge needed during deployment. Qualitative data were sorted by frequencies and similarities and clustered accordingly. Results Of 121 invitations sent out, 55 (46%) were completed and returned. Of these respondents, 24% did not feel sufficiently prepared for the deployment, and 69% did not undertake additional education for their missions. Insufficient preparedness involved equipment, drugs, regional anesthesia, and related management. Conclusions As the lack of preparation and relevant training can create precarious situations, anesthesiologists and deploying agencies should improve preparedness for anesthesia personnel. (Disaster Med Public Health Preparedness. 2013;0;1-5

Evaluation of New Anti-Infective Drugs for the Treatment of Vascular Access Device-Associated Bacteremia and Fungemia

For clinical trials of anti-infective drugs for the treatment of vascular access device-related bloodstream infections, patients should be identified and enrolled on the basis of current standards for the clinical diagnosis of such infections. To ensure comparability of patients, only those infected with staphylococci and Candida species should be included. A prospective, randomized, double-blind design is recommended. Future protocols may include abbreviated courses of therapy, treatment with combinations of drugs, or a progression from parenteral to oral therapy. Clinical response is judged as cure, failure, or indeterminate response; there is no "improved” category. Microbiological response is categorized as eradication, persistence, or relapse and is of paramount importance. Several months of follow-up may be necessary for the detection of late relapses or metastatic infections. This guideline does not apply to studies of bacteremia or fungemia secondary to non-device-related, organ-based primary infections (e.g., pneumonia, urinary tract infection), which should be assessed in relation to the primary disorde

Evaluation of a portable image overlay projector for the visualisation of surgical navigation data: phantom studies

Introduction: Presenting visual feedback for image-guided surgery on a monitor requires the surgeon to perform time-consuming comparisons and diversion of sight and attention away from the patient. Deficiencies in previously developed augmented reality systems for image-guided surgery have, however, prevented the general acceptance of any one technique as a viable alternative to monitor displays. This work presents an evaluation of the feasibility and versatility of a novel augmented reality approach for the visualisation of surgical planning and navigation data. The approach, which utilises a portable image overlay device, was evaluated during integration into existing surgical navigation systems and during application within simulated navigated surgery scenarios. Methods: A range of anatomical models, surgical planning data and guidance information taken from liver surgery, cranio-maxillofacial surgery, orthopaedic surgery and biopsy were displayed on patient-specific phantoms, directly on to the patient's skin and on to cadaver tissue. The feasibility of employing the proposed augmented reality visualisation approach in each of the four tested clinical applications was qualitatively assessed for usability, visibility, workspace, line of sight and obtrusiveness. Results: The visualisation approach was found to assist in spatial understanding and reduced the need for sight diversion throughout the simulated surgical procedures. The approach enabled structures to be identified and targeted quickly and intuitively. All validated augmented reality scenes were easily visible and were implemented with minimal overhead. The device showed sufficient workspace for each of the presented applications, and the approach was minimally intrusiveness to the surgical scene. Conclusion: The presented visualisation approach proved to be versatile and applicable to a range of image-guided surgery applications, overcoming many of the deficiencies of previously described AR approaches. The approach presents an initial step towards a widely accepted alternative to monitor displays for the visualisation of surgical navigation dat

Functional map of arrestin binding to phosphorylated opsin, with and without agonist

Arrestins desensitize G protein-coupled receptors (GPCRs) and act as mediators of signalling. Here we investigated the interactions of arrestin-1 with two functionally distinct forms of the dim-light photoreceptor rhodopsin. Using unbiased scanning mutagenesis we probed the individual contribution of each arrestin residue to the interaction with the phosphorylated apo-receptor (Ops-P) and the agonist-bound form (Meta II-P). Disruption of the polar core or displacement of the C-tail strengthened binding to both receptor forms. In contrast, mutations of phosphate-binding residues (phosphosensors) suggest the phosphorylated receptor C-terminus binds arrestin differently for Meta II-P and Ops-P. Likewise, mutations within the inter-domain interface, variations in the receptor-binding loops and the C-edge of arrestin reveal different binding modes. In summary, our results indicate that arrestin-1 binding to Meta II-P and Ops-P is similarly dependent on arrestin activation, although the complexes formed with these two receptor forms are structurally distinct

Differential Regulation of Inducible Nitric Oxide Synthase Production in Bovine and Caprine Macrophages

Inducible nitric oxide synthase (iNOS) regulation in human and murine macrophages in vitro differs considerably. In this study, expression of macrophage iNOS in ruminants was addressed. Nitric oxide (NO) output by cattle and goat macrophages was as different as that by human and mouse macrophages. Bovine macrophages activated by heated Salmonella dublin or lipopolysaccharide (LPS) expressed high levels of iNOS mRNA, protein, and enzyme activity. Analogously cultured caprine macrophages did not respond to these and other activators by NO generation and iNOS expression. The lack of response was not due to general unresponsiveness to stimuli. Caprine iNOS mRNA was induced by stimulation of caprine macrophages with LPS, as shown by reverse transcription polymerase chain reaction. The level of mRNA expression in activated goat macrophages was lower than in resting bovine macrophages. A caprine 372-bp iNOS mRNA fragment that was sequenced closely resembled the bovine counterpart. This points to species-specific iNOS gene regulatio