Interaction between NOD2 and CARD9 involves the NOD2 NACHT and the linker region between the NOD2 CARDs and NACHT domain.

NOD2 activation by muramyl dipeptide causes a proinflammatory immune response in which the adaptor protein CARD9 works synergistically with NOD2 to drive p38 and c-Jun N-terminal kinase (JNK) signalling. To date the nature of the interaction between NOD2 and CARD9 remains undetermined. Here we show that this interaction is not mediated by the CARDs of NOD2 and CARD9 as previously suggested, but that NOD2 possesses two interaction sites for CARD9; one in the CARD-NACHT linker and one in the NACHT itself.This work was funded by a Wellcome Trust Career Development Fellowship (WT085090MA) to TPM and a Medical Research Council grant (U117565398) to KR. RP and JPB were supported by BBSRC Doctoral Training Grants.This is the final published version of the article, which can also be found on the publisher's website at: http://www.sciencedirect.com/science/article/pii/S0014579314004979

Email for communicating results of diagnostic medical investigations to patients.

As medical care becomes more complex and the ability to test for conditions grows, pressure on healthcare providers to convey increasing volumes of test results to patients is driving investigation of alternative technological solutions for their delivery. This review addresses the use of email for communicating results of diagnostic medical investigations to patients. To assess the effects of using email for communicating results of diagnostic medical investigations to patients, compared to SMS/ text messaging, telephone communication or usual care, on outcomes, including harms, for health professionals, patients and caregivers, and health services. We searched: the Cochrane Consumers and Communication Review Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (OvidSP) (1950 to January 2010), EMBASE (OvidSP) (1980 to January 2010), PsycINFO (OvidSP) (1967 to January 2010), CINAHL (EbscoHOST) (1982 to February 2010), and ERIC (CSA) (1965 to January 2010). We searched grey literature: theses/dissertation repositories, trials registers and Google Scholar (searched July 2010). We used additional search methods: examining reference lists and contacting authors. Randomised controlled trials, quasi-randomised trials, controlled before and after studies and interrupted time series studies of interventions using email for communicating results of any diagnostic medical investigations to patients, and taking the form of 1) unsecured email 2) secure email or 3) web messaging. All healthcare professionals, patients and caregivers in all settings were considered. Two review authors independently assessed the titles and abstracts of retrieved citations. No studies were identified for inclusion. Consequently, no data collection or analysis was possible. No studies met the inclusion criteria, therefore there are no results to report on the use of email for communicating results of diagnostic medical investigations to patients. In the absence of included studies, we can draw no conclusions on the effects of using email for communicating results of diagnostic medical investigations to patients, and thus no recommendations for practice can be stipulated. Further well-designed research should be conducted to inform practice and policy for communicating patient results via email, as this is a developing area

Email for the coordination of healthcare appointments and attendance reminders.

Email is a popular and commonly-used method of communication, but its use in health care is not routine. Where email communication has been utilised in health care, its purposes have included the coordination of healthcare appointments and attendance reminders, but the effects of using email in this way are not known. This review considers the use of email for the coordination of healthcare appointments and reminders for attendance; particularly scheduling, rescheduling and cancelling healthcare appointments, and providing prompts/reminders for attendance at appointments. To assess the effects of using email for the coordination of healthcare appointments and attendance reminders, compared to other forms of coordinating appointments and reminders, on outcomes for health professionals, patients and carers, and health services, including harms. We searched: the Cochrane Consumers and Communication Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (OvidSP) (1950 to January 2010), EMBASE (OvidSP) (1980 to January 2010), PsycINFO (OvidSP) (1967 to January 2010), CINAHL (EbscoHOST) (1982 to February 2010),and ERIC (CSA) (1965 to January 2010). We searched grey literature: theses/dissertation repositories, trials registers and Google Scholar (searched July 2010). We used additional search methods: examining reference lists and contacting authors. Randomised controlled trials, quasi-randomised trials, controlled before and after studies and interrupted time series studies of interventions that use email for scheduling health appointments, for reminders for a scheduled health appointment or for ongoing coordination of health appointments and that took the form of 1) unsecured email 2) secure email or 3) web messaging. All healthcare professionals, patients and caregivers in all settings were considered. Two review authors independently assessed the titles and abstracts of retrieved citations. No studies were identified for inclusion. Consequently, no data collection or analysis was possible. No studies met the inclusion criteria, therefore there are no results to report on the use of email for the coordination of healthcare appointments and attendance reminders. No conclusions on the effects of using email for the coordination of healthcare appointments and attendance reminders could be made and thus no recommendations for practice can be stipulated. Given the significant theoretical opportunities that email presents, there is a need for rigorous studies addressing the review question, but this may involve addressing barriers concerning trial development and implementation

Email for the provision of information on disease prevention and health promotion.

Email is a popular and commonly used method of communication, but its use in health care is not routine. Its application in health care has included the provision of information on disease prevention and health promotion, but the effects of using email in this way are not known. This review assesses the use of email for the provision of information on disease prevention and health promotion. To assess the effects of email for the provision of information on disease prevention and health promotion, compared to standard mail or usual care, on outcomes for healthcare professionals, patients and caregivers, and health services, including harms. We searched: the Cochrane Consumers and Communication Review Group Specialised Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (1950 to January 2010), EMBASE (1980 to January 2010), CINAHL (1982 to February 2010), ERIC (1965 to January 2010) and PsycINFO (1967 to January 2010). We searched grey literature: theses/dissertation repositories, trials registers and Google Scholar (searched July 2010). We used additional search methods: examining reference lists, contacting authors. Randomised controlled trials, quasi-randomised trials, controlled before and after studies and interrupted time series studies examining interventions where email is used by healthcare professionals to provide information to patients on disease prevention and health promotion, and taking the form of 1) unsecured email 2) secure email or 3) web messaging. We considered healthcare professionals or associated administrative staff as participants originating the email communication, and patients and caregivers as participants receiving the email communication, in all settings. Email communication was one-way from healthcare professionals or associated administrative staff originating the email communication, to patients or caregivers receiving the email communication. Two authors independently assessed the risk of bias of included studies and extracted data. We contacted study authors for additional information. We assessed risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. For continuous outcome measures, we report effect sizes as mean differences (MDs). For dichotomous outcome measures, we report effect sizes as odds ratios (ORs). We conducted a meta-analysis for one primary health service outcome, comparing email communication to standard mail, and report this result as an OR. We included six randomised controlled trials involving 8372 people. All trials were judged to be at high risk of bias for at least one domain. Four trials compared email communication to standard mail and two compared email communication to usual care. For the primary health service outcome of uptake of preventive screening, there was no difference between email and standard mail (OR 0.93; 95% CI 0.69 to 1.24). For both comparisons (email versus standard mail and email versus usual care) there was no difference between the groups for patient or caregiver understanding and support. Results were inconclusive for patient or caregiver behaviours and actions. For email versus usual care only, there was no significant difference between groups for the primary outcome of patient health status and well-being. No data were reported relating to healthcare professionals or harms. The evidence on the use of email for the provision of information on disease prevention and health promotion was weak, and therefore inadequate to inform clinical practice. The available trials mostly provide inconclusive, or no evidence for the outcomes of interest in this review. Future research needs to use high-quality study designs that take advantage of the most recent developments in information technology, with consideration of the complexity of email as an intervention

Email for clinical communication between patients/caregivers and healthcare professionals.

BACKGROUND: Email is a popular and commonly-used method of communication, but its use in health care is not routine. Where email communication has been demonstrated in health care this has included its use for communication between patients/caregivers and healthcare professionals for clinical purposes, but the effects of using email in this way is not known.This review addresses the use of email for two-way clinical communication between patients/caregivers and healthcare professionals. OBJECTIVES: To assess the effects of healthcare professionals and patients using email to communicate with each other, on patient outcomes, health service performance, service efficiency and acceptability. SEARCH METHODS: We searched: the Cochrane Consumers and Communication Review Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (OvidSP) (1950 to January 2010), EMBASE (OvidSP) (1980 to January 2010), PsycINFO (OvidSP) (1967 to January 2010), CINAHL (EbscoHOST) (1982 to February 2010) and ERIC (CSA) (1965 to January 2010). We searched grey literature: theses/dissertation repositories, trials registers and Google Scholar (searched July 2010). We used additional search methods: examining reference lists, contacting authors. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised trials, controlled before and after studies and interrupted time series studies examining interventions using email to allow patients to communicate clinical concerns to a healthcare professional and receive a reply, and taking the form of 1) unsecured email 2) secure email or 3) web messaging. All healthcare professionals, patients and caregivers in all settings were considered. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias of included studies and extracted data. We contacted study authors for additional information. We assessed risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. For continuous measures, we report effect sizes as mean differences (MD). For dichotomous outcome measures, we report effect sizes as odds ratios and rate ratios. Where it was not possible to calculate an effect estimate we report mean values for both intervention and control groups and the total number of participants in each group. Where data are available only as median values it is presented as such. It was not possible to carry out any meta-analysis of the data. MAIN RESULTS: We included nine trials enrolling 1733 patients; all trials were judged to be at risk of bias. Seven were randomised controlled trials; two were cluster-randomised controlled designs. Eight examined email as compared to standard methods of communication. One compared email with telephone for the delivery of counselling. When email was compared to standard methods, for the majority of patient/caregiver outcomes it was not possible to adequately assess whether email had any effect. For health service use outcomes it was not possible to adequately assess whether email has any effect on resource use, but some results indicated that an email intervention leads to an increased number of emails and telephone calls being received by healthcare professionals. Three studies reported some type of adverse event but it was not clear if the adverse event had any impact on the health of the patient or the quality of health care. When email counselling was compared to telephone counselling only patient outcomes were measured, and for the majority of measures there was no difference between groups. Where there were differences these showed that telephone counselling leads to greater change in lifestyle modification factors than email counselling. There was one outcome relating to harm, which showed no difference between the email and the telephone counselling groups. There were no primary outcomes relating to healthcare professionals for either comparison. AUTHORS' CONCLUSIONS: The evidence base was found to be limited with variable results and missing data, and therefore it was not possible to adequately assess the effect of email for clinical communication between patients/caregivers and healthcare professionals. Recommendations for clinical practice could not be made. Future research should ideally address the issue of missing data and methodological concerns by adhering to published reporting standards. The rapidly changing nature of technology should be taken into account when designing and conducting future studies and barriers to trial development and implementation should also be tackled. Potential outcomes of interest for future research include cost-effectiveness and health service resource use

High-Level Bacterial Expression and Purification of Apicomplexan Micronemal Proteins for Structural Studies

Micronemal protein secretion from apicomplexan parasites like Toxoplasma gondii is responsible for the directional attachment of the parasite to the host in a step critical in invasion. Despite the medical importance and the justification of micronemal proteins as drug targets, very little is known about their specific mechanisms of host attachment and the nature of their host receptors. Here we describe the cloning, high-level expression in Escherichia coli and purification of the N-terminal domain of the adhesive protein MIC1 (MIC1-NT) from Toxoplasma gondii as a thioredoxin fusion protein; a protein fragment with 16 cysteines and 8 potential disulphide bonds. The final, cleaved product is close to 100% pure by SDS-PAGE and the yield was about 15mg/L. The protein fragment is soluble, stable and suitable for structural and functional studies. MIC1-NT was characterised by mass spectroscopy and size-exclusion chromatography to prove its presence in monomeric form. The 1D 1H and 2D (1H-15N) HSQC spectra reveal that the protein is well structured. The same strategy was applied to two additional cysteine rich micronemal proteins giving similar results to MIC1-NT. Our results demonstrate that our approach can have a wider application in the recombinant expression, structural and functional studies of the extended family of micronemal proteins

"Communicate to vaccinate" : the development of a taxonomy of communication interventions to improve routine childhood vaccination

Vaccination is a cost-effective public health measure and is central to the Millennium Development Goal of reducing child mortality. However, childhood vaccination coverage remains sub-optimal in many settings. While communication is a key feature of vaccination programmes, we are not aware of any comprehensive approach to organising the broad range of communication interventions that can be delivered to parents and communities to improve vaccination coverage. Developing a classification system (taxonomy) organised into conceptually similar categories will aid in: understanding the relationships between different types of communication interventions; facilitating conceptual mapping of these interventions; clarifying the key purposes and features of interventions to aid implementation and evaluation; and identifying areas where evidence is strong and where there are gaps. This paper reports on the development of the 'Communicate to vaccinate' taxonomy.; The taxonomy was developed in two stages. Stage 1 included: 1) forming an advisory group; 2) searching for descriptions of interventions in trials (CENTRAL database) and general health literature (Medline); 3) developing a sampling strategy; 4) screening the search results; 5) developing a data extraction form; and 6) extracting intervention data. Stage 2 included: 1) grouping the interventions according to purpose; 2) holding deliberative forums in English and French with key vaccination stakeholders to gather feedback; 3) conducting a targeted search of grey literature to supplement the taxonomy; 4) finalising the taxonomy based on the input provided.; The taxonomy includes seven main categories of communication interventions: inform or educate, remind or recall, teach skills, provide support, facilitate decision making, enable communication and enhance community ownership. These categories are broken down into 43 intervention types across three target groups: parents or soon-to-be-parents; communities, community members or volunteers; and health care providers.; Our taxonomy illuminates and organises this field and identifies the range of available communication interventions to increase routine childhood vaccination uptake. We have utilised a variety of data sources, capturing information from rigorous evaluations such as randomised trials as well as experiences and knowledge of practitioners and vaccination stakeholders. The taxonomy reflects current public health practice and can guide the future development of vaccination programmes

Co-crystallisation and humanisation of an anti-HER2 single-domain antibody as a theranostic tool

Human epidermal growth factor receptor-2 (HER2) is a well-recognised biomarker associated with 25% of breast cancers. In most cases, early detection and/or treatment correlates with an increased chance of survival. This study, has identified and characterised a highly specific anti-HER2 single-domain antibody (sdAb), NM-02, as a potential theranostic tool. Complete structural description by X-ray crystallography has revealed a non-overlapping epitope with current anti-HER2 antibodies. To reduce the immunogenicity risk, NM-02 underwent a humanisation process and retained wild type-like binding properties. To further de-risk the progression towards chemistry, manufacturing and control (CMC) we performed full developability profiling revealing favourable thermal and physical biochemical ‘drug-like’ properties. Finally, the application of the lead humanised NM-02 candidate (variant K) for HER2-specific imaging purposes was demonstrated using breast cancer HER2+/BT474 xenograft mice