Potential routes for indirect transmission of African swine fever virus into domestic pig herds

Following its introduction into Georgia in 2007, African swine fever virus (ASFV) has become widespread on the European continent and in Asia. In many cases, the exact route of introduction into domestic pig herds cannot be determined, but most introductions are attributed to indirect virus transmission. In this review, we describe knowledge gained about different matrices that may allow introduction of the virus into pig herds. These matrices include uncooked pig meat, processed pig‐derived products, feed, matrices contaminated with the virus and blood‐feeding invertebrates. Knowledge gaps still exist, and both field studies and laboratory research are needed to enhance understanding of the risks for ASFV introductions, especially via virus‐contaminated materials, including bedding and feed, and via blood‐feeding, flying insects. Knowledge obtained from such studies can be applied to epidemiological risk assessments for the different transmission routes. Such assessments can be utilized to help predict the most effective biosecurity and control strategies.     

Physiological processes of inflammation and edema initiated by sustained mechanical loading in subcutaneous tissues: A scoping review

Deep tissue injuries are pressure ulcers which initiate in the subcutaneous tissues and extend through a bottom‐up pathway. Once deep tissue injuries are visual at skin level, serious irreversible tissue damage has already occurred. In pressure ulcer development, inflammation and edema are coupled physiological processes associated with tissue damage arising due to sustained mechanical loading. This study aimed to provide an in‐depth overview of the physiological processes of inflammation and edema initiated by sustained mechanical loading in subcutaneous tissues, in the context of pressure ulceration. A scoping review was performed according to the framework by Arksey and O'Malley. The databases MEDLINE, EMBASE, Web of Science, and Scopus, and the reference lists of included studies were searched for in vivo (animal, human), and in vitro studies matching the study objectives (from inception to 28 May 2018). No restrictions for inclusion were applied for study design, setting, participants, and year of publication. A total of 12 studies were included, varying in study design, sample characteristics, amount and duration of mechanical loads that were applied, follow‐up time, and assessment methods. Neutrophil infiltration and edema occur in the subcutaneous tissues nearly immediately after the application of load on soft tissues. The amount of neutrophils and edema increase in the first days after the mechanical insult and decrease once healing has been initiated and no supplementary mechanical load was applied. One study indicated that edema may extend up to the level of the dermo‐epidermal junction. Further research should focus on how deep tissue inflammation and edema are reflected into unique tissue changes at skin level, and how abnormal inflammatory responses manifest (e.g. when the nervous system is not functioning normally).     

The transition from patient to mental health peer worker: A grounded theory approach

Peer workers are increasingly being engaged in contemporary mental healthcare. To become a peer worker, patients must evolve from having a patient identity to a peer worker identity. This study aims to understand how mental health peer workers experience their transition and how it affects their view of themselves and their direct working context. A grounded theory approach was used. Seventeen mental health peer workers in Belgium were recruited through theoretical sampling. Semi‐structured interviews were conducted and analysed according to the constant comparative method. The results indicate that novice peer workers experience peer work as an opportunity to liberate themselves from the process of mental suffering and realise an acceptable form of personal self‐maintenance. As peer workers become more experienced, they are confronted with external factors that influence their self‐maintenance and personal development. Experiencing clarity in their duties and responsibilities, equality, and transparency in the workplace reinforce their experience of self‐maintenance and positively influence their self‐development. Experiencing a lack of clarity in their duties and responsibilities, inequality, and lack of openness discourage peer workers’ self‐development process. These experiences challenge their personal motivations to become peer workers, which are usually linked to building a meaningful life for themselves. The insights can encourage organisations to build up a supportive environment collaboratively with peer workers and ensure that peer workers can exert their authentically unique role in mental healthcare.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity

The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near −65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor–based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure–function relationships of the light-gated pore.Discovery and engineering of the microbial opsin genes not only has stimulated basic science investigation into the structure–function relationships of proteins involved in light-triggered ion flow but also has opened up opportunities for biological investigation (reviewed in ref. 1) via the technique of optogenetics, which involves targeting these genes and corresponding optical stimuli to control activity within specified types of cells within intact and functioning biological systems. For example, optogenetics has been used to identify causally the brain cells and projections involved in behaviors relevant to memory formation, affective states, and motor function, among many other discoveries (2–4). For the channelrhodopsins, an important member of this protein family widely used in optogenetics (5, 6), the light-activated cation-conducting channel pore has been the subject of structural investigation, both because of curiosity regarding the physical properties of its ion conduction and because the creation of inhibitory channels had been sought for optogenetic applications. Converging lines of work recently achieved the latter goal; resolving the high-resolution structure of channelrhodopsin (7) allowed a principled structure-guided approach to engineering for chloride selectivity by testing an electrostatic model for pore function (8, 9). Subsequently, by screening the genome of the Guillardia theta microbe, two naturally occurring light-gated chloride-conducting channelrhodopsins (10) were identified.Because optogenetic control of behavior has not yet been demonstrated with chloride channelrhodopsins, and to test further integrative ideas regarding pore function from structural considerations as shown here, we sought to design and test the next generation of enhanced chloride channels (iC++ and SwiChR++). Along the way, we provide the initial test of the hypothesis that light-activated channels will be more efficient tools than pumps for optogenetic neuronal inhibition at the cellular level, demonstrate the initial utility of light-gated chloride channels in controlling behavior in freely moving animals, and reveal key principles regarding the functional selectivity of light-gated ion channel pores.     

TIMI risk score underestimates prognosis in unstable angina/non-ST segment elevation myocardial infarction

OBJECTIVES: To determine the value of the TIMI risk score in the individual risk stratification of patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: TIMI risk score is a validated tool to identify groups of patients at high risk for major cardiac events. Its prognostic value in individual patients with current diagnostic tools and therapy is unknown. METHODS: TIMI risk score was assessed in patients with UA/NSTEMI admitted to six Belgian hospitals and related to clinical outcome at 30 days. RESULTS: Of the 500 patients enrolled, 49.4% were placed in the low TIMI risk group (score = 0-3) and 50.6% in the high-risk group (score = 4-7). Multivariate analysis identified raised cardiac markers and invasive strategy, but not high TIMI risk score as independent predictors of death and new myocardial infarction (MI). Moreover, the incidence of death and MI in the low TIMI risk group with positive cardiac markers was not lower than in the high TIMI risk group with positive markers: 15.1% versus 17.8% (P = 0.7). CONCLUSIONS: TIMI risk score is of limited value for individual risk stratification. The presence of positive cardiac markers (troponin) appears to be a more powerful prognostic marker.     

A SHORT NOTE ON ECONOMIC DEVELOPMENT AND SOCIOECONOMIC INEQUALITY IN FEMALE BODY WEIGHT

The origin of the obesity epidemic in developing countries is still poorly understood. It has been prominently argued that economic development provides a natural interpretation of the growth in obesity. This paper tests the main aggregated predictions of the theoretical framework to analyze obesity. Average body weight and health inequality should be associated with economic development. Both hypotheses are confirmed: we find higher average female body weight in economically more advanced countries. In relatively nondeveloped countries, obesity is a phenomenon of the socioeconomic elite. With economic development, obesity shifts toward individuals with lower socioeconomic status. Copyright © 2013 John Wiley & Sons, Ltd.