Biocontrol of cereal crop diseases using streptomycetes

A growing world population and an increasing demand for greater food production requires that crop losses caused by pests and diseases are dramatically reduced. Concurrently, sustainability targets mean that alternatives to chemical pesticides are becoming increasingly desirable. Bacteria in the plant root microbiome can protect their plant host against pests and pathogenic infection. In particular, Streptomyces species are well-known to produce a range of secondary metabolites that can inhibit the growth of phytopathogens. Streptomyces are abundant in soils and are also enriched in the root microbiomes of many different plant species, including those grown as economically and nutritionally valuable cereal crops. In this review we discuss the potential of Streptomyces to protect against some of the most damaging cereal crop diseases, particularly those caused by fungal pathogens. We also explore factors that may improve the efficacy of these strains as biocontrol agents in situ, as well as the possibility of exploiting plant mechanisms that enable the recruitment of microbial species from the soil to the root microbiome. We argue that a greater understanding of these mechanisms may enable the development of protective plant root microbiomes with a greater abundance of beneficial bacteria such as Streptomyces species

Protocol for a systematic review of the impact of resuscitation fluids on the microcirculation after haemorrhagic shock in animal models

BACKGROUND: Modern resuscitation strategies following haemorrhagic shock are influenced by global haemodynamic parameters such as blood pressure and cardiac output. Microcirculatory dysfunction in this context may persist even after restoration of satisfactory global parameters. Additional monitoring of the microcirculatory function may therefore be warranted in order to facilitate goal-directed therapy at a tissue oxygenation level. Although such a phenomenon is recognised in the case of sepsis, clinical evidence regarding the behaviour of the microcirculation following the delivery of resuscitation fluids after haemorrhagic shock is sparse. A summation of the current state of pre-clinical evidence is justified in order to direct avenues for future clinical research. METHODS/DESIGN: Systematic review methodology will be utilised in order to identify relevant studies, assess for bias, and extract data for analysis. Medical databases will be searched to find pre-clinical studies that monitor the microcirculatory function following haemorrhagic shock and subsequent fluid resuscitation. Different fluid types (e.g. blood products, crystalloid, and colloid fluids) will be compared. The search strategy will combine terms for the animal model, resuscitation fluid, and microcirculatory parameters. Randomised and non-randomised experiments, as well as case series, will be eligible for inclusion. Specific quality assessment tools for pre-clinical research will be used depending on study design. A combination of narrative and meta-analysis techniques will be used for the synthesis of data. DISCUSSION: The choice of type, sequence, and quantity of resuscitation fluid following haemorrhagic shock is controversial, and the optimal strategy for restoration of microcirculatory function is yet unknown. A detailed examination of pre-clinical data regarding the microcirculation is timely and will enable a focussed approach to clinical research for the improvement of resuscitation following haemorrhagic shock. SYSTEMATIC REVIEW REGISTRATION: Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-015-0113-4) contains supplementary material, which is available to authorized users

Observational study of the effects of traumatic injury, haemorrhagic shock and resuscitation on the microcirculation: a protocol for the MICROSHOCK study

Introduction: The microcirculation is the physiological site of oxygen and substrate exchange. Its effectiveness during circulatory shock is vital for the perfusion of tissues, and has a bearing on subsequent organ function and prognosis. Microcirculatory dysfunction following traumatic haemorrhagic shock (THS) has been understudied compared with other pathologies such as sepsis. The aim of the MICROSHOCK study is to investigate changes seen in the microcirculation of patients following THS, and to assess its response to resuscitation. A greater understanding of the behaviour and mechanisms of microcirculatory dysfunction in this context may direct future avenues of goal-directed resuscitation for these patients. Methods and analysis: This multicentre prospective longitudinal observational study includes patients who present as an emergency with THS. Microcirculatory parameters are recorded using sublingual incident dark field microscopy alongside measurements of global flow (oesophageal Doppler and transthoracic echocardiography). Patients are enrolled into the study as soon as feasible after they arrive in hospital, and then at subsequent daily time points. Blood samples are taken for investigation into the mechanisms of microcirculatory dysfunction. Sequential Organ Failure Assessment scores will be analysed with microcirculatory parameters to determine whether they correlate with greater fidelity than more conventional, global circulatory parameters. Ethics and dissemination: Research Ethics Committee approval has been granted for this study (Reference: 14/YH/0078). Owing to the nature of THS, capacity for informed consent will be absent on patient enrolment. This will be addressed according to the Mental Health Capacity Act 2005. The physician in charge of the patient's care (nominated consultee) may consent on behalf of the patient. Consent will also be sought from a personal consultee (close relative or friend). After capacity is regained, the participant will be asked for their consent. Results will be submitted for publication in peer-reviewed journal format and presented at relevant academic meetings

Searching for the Optimal Fluid to Restore Microcirculatory Flow Dynamics After Haemorrhagic Shock:A Systematic Review of Preclinical Studies

BACKGROUND: Increased microcirculatory flow and perfusion has been reported to improve clinical outcomes following shock. The optimal resuscitation fluid to restore the flow dynamics of the microcirculation is unknown. This review summarises the preclinical literature in order to inform the direction and most important hypotheses for future clinical interventional studies.METHODS: Standard systematic review methodology was utilized, and registered with the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES). Medline and Embase (via OVID SP) and SCOPUS were searched for all preclinical studies of haemorrhagic shock that compared fluid resuscitation of any kind (e.g. blood products, crystalloids, colloids, or haemoglobin based oxygen carriers) to another fluid or haemorrhage only, and reported at least one microcirculatory physical endpoint (such as flow rate, velocity, vessel diameter, functional capillary density or glycocalyx thickness). Risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. Translatability was also assessed for each study based on the most common recommendations.RESULTS: There were 3103 potential studies of interest, of which 71 studies fulfilled all eligibility criteria. There were 62 rodent, 5 canine and 4 porcine studies. Flow rate, velocity, and vessel diameter were the most commonly reported endpoints. Studies reported the importance of the presence of haemoglobin, as well as osmotic potential and viscosity in providing optimal restoration of microcirculatory flow dynamics. Others reported the restoration of the endothelial glycocalyx and attenuation of inflammation as important properties for the choice of fluid. All studies were at potential risk of bias due to unclear randomization, concealment, and blinding. There were important threats to translatability for all studies.CONCLUSION: The ideal resuscitation fluid for restoration of the microcirculation following haemorrhagic shock is likely to contain a preparation of haemoglobin, favour higher oncotic potential and viscosity, protect and reconstitute the endothelium, and attenuate inflammation. These hypotheses that are derived from preclinical research warrant further exploration in the clinical context.</p

A randomised controlled feasibility trial of a BabyWASH household playspace: the CAMPI study

Background Water, sanitation and hygiene (WASH) interventions should support infant growth but trial results are inconsistent. Frequently, interventions do not consider behaviours or transmission pathways specific to age. A household playspace (HPS) is one intervention component which may block faecal-oral transmission. This study was a two-armed, parallel-group, randomised, controlled feasibility trial of a HPS in rural Ethiopia. It aimed to recommend proceeding to a definitive trial. Secondary outcomes included effects on infant health, injury prevention and women’s time. Methods November 2019−January 2020 106 households were identified and assessed for eligibility. Recruited households (N = 100) were randomised (blinded prior to the trial start) to intervention or control (both n = 50). Outcomes included recruitment, attrition, adherence, and acceptability. Data were collected at baseline, two and four weeks. Findings Recruitment met a priori criteria (≥80%). There was no loss to follow-up, and no non-use, meeting adherence criteria (both ≤10%). Further, 48.0% (95% CI 33.7−62.6; n = 24) of households appropriately used and 56.0% (41.3−70.0; n = 28) cleaned the HPS over four weeks, partly meeting adherence criteria (≥50%). For acceptability, 41.0% (31.3−51.3; n = 41) of infants were in the HPS during random visits, failing criteria (≥50%). Further, the proportion of HPS use decreased during some activities, failing criteria (no decrease in use). A modified Barrier Analysis described good acceptability and multiple secondary benefits, including on women’s time burden and infant injury prevention. Interpretation Despite failing some a priori criteria, the trial demonstrated mixed adherence and good acceptability among intervention households. A definitive trial to determine efficacy is warranted if recommended adjustments are made

Feasibility study for supporting medication adherence for adults with cystic fibrosis: mixed-methods process evaluation

Objectives: To undertake a process evaluation of an adherence support intervention for people with cystic fibrosis (PWCF), to assess its feasibility and acceptability. Setting: Two UK cystic fibrosis (CF) units. Participants: Fourteen adult PWCF; three professionals delivering adherence support (‘interventionists’); five multi-disciplinary CF team members. Interventions: Nebuliser with data recording and transfer capability, linked to a software platform, and strategies to support adherence to nebulised treatments facilitated by interventionists over 5 months (± 1 month). Primary and secondary measures: Feasibility and acceptability of the intervention, assessed through semistructured interviews, questionnaires, fidelity assessments and click analytics. Results: Interventionists were complimentary about the intervention and training. Key barriers to intervention feasibility and acceptability were identified. Interventionists had difficulty finding clinic space and time in normal working hours to conduct review visits. As a result, fewer than expected intervention visits were conducted and interviews indicated this may explain low adherence in some intervention arm participants. Adherence levels appeared to be >100% for some patients, due to inaccurate prescription data, particularly in patients with complex treatment regimens. Flatlines in adherence data at the start of the study were linked to device connectivity problems. Content and delivery quality fidelity were 100% and 60%–92%, respectively, indicating that interventionists needed to focus more on intervention ‘active ingredients’ during sessions. Conclusions: The process evaluation led to 14 key changes to intervention procedures to overcome barriers to intervention success. With the identified changes, it is feasible and acceptable to support medication adherence with this intervention. Trial registration number: ISRCTN13076797; Results

"An Impediment to Living Life": Why and How Should We Measure Stiffness in Polymyalgia Rheumatica?

Objectives: To explore patients’ concepts of stiffness in polymyalgia rheumatica (PMR), and how they think stiffness should be measured. Methods: Eight focus groups were held at three centres involving 50 patients with current/previous PMR. Each group had at least one facilitator and one rapporteur making field notes. An interview schedule was used to stimulate discussion. Interviews were recorded, transcribed and analysed using an inductive thematic approach. Results: Major themes identified were: symptoms: pain, stiffness and fatigue; functional impact; impact on daily schedule; and approaches to measurement. The common subtheme for the experience of stiffness was “difficulty in moving”, and usually considered as distinct from the experience of pain, albeit with a variable overlap. Some participants felt stiffness was the “overwhelming” symptom, in that it prevented them carrying out “fundamental activities” and “generally living life”. Diurnal variation in stiffness was generally described in relation to the daily schedule but was not the same as stiffness severity. Some participants suggested measuring stiffness using a numeric rating scale or a Likert scale, while others felt that it was more relevant and straightforward to measure difficulty in performing everyday activities rather than about stiffness itself. Conclusions: A conceptual model of stiffness in PMR is presented where stiffness is an important part of the patient experience and impacts on their ability to live their lives. Stiffness is closely related to function and often regarded as interchangeable with pain. From the patients’ perspective, visual analogue scales measuring pain and stiffness were not the most useful method for reporting stiffness; participants preferred numerical rating scales, or assessments of function to reflect how stiffness impacts on their daily lives. Assessing function may be a pragmatic solution to difficulties in quantifying stiffness