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Background: Exacerbations in chronic obstructive pulmonary disease (COPD) is a major health problem and telemonitoring has been suggested as a strategy to detect early signs. There is however little information on user experience regarding use of these systems. Aim: The aim of the study was to explore perceptions of the use of a home telemonitoring system in patients with COPD. Methods: Interviews were carried out with eight women and five men with COPD, who participated in a project aimed at developing and evaluating a telemonitoring system. The web-based system measured pulmonary function, subjective symptoms, and oxygen saturation. Participants were interviewed when they had used the system for two to four months. The Interviews were analysed using qualitative content analysis. Results: The theme A transition towards increased control and security runs through four categories: using with (in)security, affecting technical concern or confidence, providing easy access to healthcare, and increasing control over the disease. The participants reported various perceptions of using the telemonitoring system with initial feelings of insecurity, both in terms of operating the system and in terms of their disease. However, the practical management of the system became easier with time and participants gradually gained confidence and improved their self-management. New technology was perceived as an important complement to existing healthcare, but the importance of maintaining a human contact in real life or through the telemonitoring system was emphasized. Conclusions: Telemonitoring can be a valuable complement to healthcare, leading to improved self-management and increased control.

BackgroundMany telehealth systems have been designed to identify signs of exacerbations in patients with chronic obstructive pulmonary disease (COPD), but few previous studies have reported the nature of recorded lung function data and what variations to expect in this group of individuals. The aim of the study was to evaluate the nature of individual diurnal, day-to-day and long-term variation in important prognostic markers of COPD exacerbations by employing a telehealth system developed in-house.MethodsEight women and five men with COPD performed measurements (spirometry, pulse oximetry and the COPD assessment test (CAT)) three times per week for 4–6 months using the telehealth system. Short-term and long-term individual variations were assessed using the relative density and weekly means respectively. Quality of the spirometry measurements (forced expiratory volume in one second (FEV1) and inspiratory capacity (IC)) was assessed employing the criteria of American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.ResultsClose to 1100 measurements of both FEV1and IC were performed during a total of 240 patient weeks. The two standard deviation ranges for intra-individual short-term variation were approximately ±210 mL and ± 350 mL for FEV1and IC respectively. In long-term, spirometry values increased and decreased without notable changes in symptoms as reported by CAT, although it was unusual with a decrease of more than 50 mL per measurement of FEV1between three consecutive measurement days. No exacerbation occurred. There was a moderate to strong positive correlation between FEV1and IC, but weak or absent correlation with the other prognostic markers in the majority of the participants.ConclusionsAlthough FEV1and IC varied within a noticeable range, no corresponding change in symptoms occurred. Therefore, this study reveals important and, to our knowledge, previously not reported information about short and long-term variability in prognostic markers in stable patients with COPD. The present data are of significance when defining criteria for detecting exacerbations using telehealth strategies.

The incidence and geographical distribution of dengue fever has increased in recent decades. The actual disease burden is unknown owing to frequent underreporting and misclassification of cases. A well-functioning system for diagnosing, treating, and reporting cases is of prime importance as disease statistics is the foundation for decisions aiming to control the disease. This study aimed to explore the hospital-based disease surveillance system in Yogyakarta, a dengue-endemic region on Java, Indonesia. Semi-structured interviews were performed with 16 informants from four hospitals, including five general practitioners, three internists, four pediatricians, and four administrative staff working with administration relating to dengue diagnostics and reporting. Data were analyzed using content analysis. A theme arose from the analysis “Dengue surveillance stands and falls by the rigor of the health system.” The theme, and underlying categories and subcategories, describes a surveillance system that in the best-case scenario works well and is likely to produce reliable dengue case data. However, there is a lack of synchronization between regulations and guidelines in different hospitals and some friction between regulatory bodies and the care provider. Knowledge among the staff appears to vary, and many clinical and financial decisions are made rather arbitrarily, which ultimately might lead to unequal health service delivery. In conclusion, the dengue surveillance system under study could improve further, particularly by ensuring that all regulations and recommended procedures are standardized and that all staff are given the best opportunity to stay updated on dengue-related matters, clinical as well as regulatory, on a regular basis.

Background Chronic obstructive pulmonary disease (COPD) is a major health problem and an economic burden globally. There is growing interest in how electronic health (eHealth) can be used to provide efficient health care. Telemonitoring, where the patient’s health-related data is transmitted to a health care provider, can be used to detect early signs of exacerbations. A successful implementation of telemonitoring systems into clinical practice requires in-depth knowledge of the users’ preferences. Objective The aim of this study was to explore perceptions of the use of a home telemonitoring system among patients with COPD. Methods Semistructured individual interviews were carried out with 8 women and 5 men who were participants in a project aimed at developing and evaluating a telemonitoring system. The web-based telemonitoring system measured pulmonary function, subjective symptoms, and oxygen saturation. Participants were interviewed after having used the system for 2-4 months. Interview transcripts were analyzed with qualitative content analysis. Results The analysis resulted in the theme A transition toward increased control and security and four categories: using with (in)security, affecting technical concern or confidence, providing easy access to health care, and increasing control over the disease. The participants reported various perceptions of using the telemonitoring system. They expressed initial feelings of insecurity, both in terms of operating the system and in terms of their disease. However, the practical management of the telemonitoring system became easier with time; the participants gradually gained confidence and improved their self-management. New technology was perceived as an important complement to existing health care, but the importance of maintaining a human contact in real life or through the telemonitoring system was emphasized. Conclusions This study captured a transition among the participants from being insecure and experiencing technical concerns to acquiring technical confidence and improving disease management. Telemonitoring can be a valuable complement to health care, leading to increased self-knowledge, a sense of security, and improved self-management. Suggestions to improve the further development and implementation of telemonitoring systems include better patient education and the involvement of end users in the technical development process. Additional research is needed, particularly in the design of user-friendly systems, as well as in developing tools to predict which patients are most likely to find the equipment useful, as this may result in increased empowerment, improved quality of life, reduced costs, and a contribution to equity in health.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a major health problem and an economic burden globally. There is growing interest in how electronic health (eHealth) can be used to provide efficient health care. Telemonitoring, where the patient’s health-related data is transmitted to a health care provider, can be used to detect early signs of exacerbations. A successful implementation of telemonitoring systems into clinical practice requires in-depth knowledge of the users’ preferences. OBJECTIVE The aim of this study was to explore perceptions of the use of a home telemonitoring system among patients with COPD. METHODS Semistructured individual interviews were carried out with 8 women and 5 men who were participants in a project aimed at developing and evaluating a telemonitoring system. The web-based telemonitoring system measured pulmonary function, subjective symptoms, and oxygen saturation. Participants were interviewed after having used the system for 2-4 months. Interview transcripts were analyzed with qualitative content analysis. RESULTS The analysis resulted in the theme A transition toward increased control and security and four categories: using with (in)security, affecting technical concern or confidence, providing easy access to health care, and increasing control over the disease. The participants reported various perceptions of using the telemonitoring system. They expressed initial feelings of insecurity, both in terms of operating the system and in terms of their disease. However, the practical management of the telemonitoring system became easier with time; the participants gradually gained confidence and improved their self-management. New technology was perceived as an important complement to existing health care, but the importance of maintaining a human contact in real life or through the telemonitoring system was emphasized. CONCLUSIONS This study captured a transition among the participants from being insecure and experiencing technical concerns to acquiring technical confidence and improving disease management. Telemonitoring can be a valuable complement to health care, leading to increased self-knowledge, a sense of security, and improved self-management. Suggestions to improve the further development and implementation of telemonitoring systems include better patient education and the involvement of end users in the technical development process. Additional research is needed, particularly in the design of user-friendly systems, as well as in developing tools to predict which patients are most likely to find the equipment useful, as this may result in increased empowerment, improved quality of life, reduced costs, and a contribution to equity in health.

Background: Many telehealth (TH) systems have been designed to identify signs of COPD exacerbations, but few previous studies have reported the nature of recorded lung function data and what variat ...

BACKGROUND New strategies are urgently needed to support self-management for people with chronic obstructive pulmonary disease (COPD) in primary care. The use of electronic health (eHealth) solutions is promising. However, there is a lack of knowledge about how such eHealth tools should be designed in order to be perceived as relevant and useful and meet the needs and expectations of the health professionals as well as people with COPD and their relatives. OBJECTIVE The objective of this study was to explore the aspects of an eHealth tool design and content that make it relevant and useful for supporting COPD-related self-management strategies from the perspective of health care professionals, people with COPD and their relatives, and external researchers. METHODS Data were collected during the development of an eHealth tool. A cocreation process was carried out with participants from two primary care units in northern Sweden and external researchers. Individual interviews were performed with health care professionals (n=13) as well as people with COPD (n=6) and their relatives (n=2), and focus group discussions (n=9) were held with all groups of participants. Data were analyzed using qualitative content analysis. RESULTS The overarching theme, reinforcing existing support structures, reflects participant views that the eHealth tool needs to be directly applicable and create a sense of commitment in users. Moreover, participants felt that the tool needs to fit with existing routines and contexts and preferably should not challenge existing hierarchies between health care professionals and people with COPD. Important content for health care professionals and people with COPD included knowledge about self-management strategies. Videos were regarded as the most effective method for communicating such knowledge. CONCLUSIONS The cocreation in the development process enables participant perspectives and priorities to be built into the eHealth tool. This is assumed to contribute to a tool that is useful and relevant and, therefore, adopted into clinical practice and everyday life. Findings from this study can inform the development of eHealth tools for people with COPD in other contexts, as well as the development of eHealth tools for self-management support of other chronic diseases.

Background: New strategies are urgently needed to support self-management for people with chronic obstructive pulmonary disease (COPD) in primary care. The use of electronic health (eHealth) solutions is promising. However, there is a lack of knowledge about how such eHealth tools should be designed in order to be perceived as relevant and useful and meet the needs and expectations of the health professionals as well as people with COPD and their relatives. Objective: The objective of this study was to explore the aspects of an eHealth tool design and content that make it relevant and useful for supporting COPD-related self-management strategies from the perspective of health care professionals, people with COPD and their relatives, and external researchers. Methods: Data were collected during the development of an eHealth tool. A cocreation process was carried out with participants from two primary care units in northern Sweden and external researchers. Individual interviews were performed with health care professionals (n=13) as well as people with COPD (n=6) and their relatives (n=2), and focus group discussions (n=9) were held with all groups of participants. Data were analyzed using qualitative content analysis. Results: The overarching theme, reinforcing existing support structures, reflects participant views that the eHealth tool needs to be directly applicable and create a sense of commitment in users. Moreover, participants felt that the tool needs to fit with existing routines and contexts and preferably should not challenge existing hierarchies between health care professionals and people with COPD. Important content for health care professionals and people with COPD included knowledge about self-management strategies. Videos were regarded as the most effective method for communicating such knowledge. Conclusions: The cocreation in the development process enables participant perspectives and priorities to be built into the eHealth tool. This is assumed to contribute to a tool that is useful and relevant and, therefore, adopted into clinical practice and everyday life. Findings from this study can inform the development of eHealth tools for people with COPD in other contexts, as well as the development of eHealth tools for self-management support of other chronic diseases.

Background: There is a gap between evidence-based interventions and the availability of such interventions for people with chronic obstructive pulmonary disease (COPD). Aim: The aim of this study was to increase the understanding of what shapes the provision of healthcare services to people with COPD in primary care, and what healthcare they are offered and actually receive. Methods: The study was conducted in primary care in Sweden. Mixed methods design was used, where qualitative and quantitative findings were merged into a joint analysis. For the qualitative component interviews were performed with healthcare professionals (n=14) from two primary care centres and analysed with qualitative content analysis. For the quantitative component one questionnaire was answered by professionals (n=18) at two centres and one questionnaire was answered by senior managers/COPD nurses at centres (n=26) in one county council. Descriptive statistical analysis was used. Results: The theme Building COPD care on shaky ground highlights driven and independent professionals that want to build a supportive COPD care with interprofessional collaboration. The shaky organisational ground is represented by a complex disease surrounded with shame, uninformed patients, professionals’ lacking competence, inadequate routines, and lacking resources. Conclusions: The mixed methods design gave a comprehensive picture of the COPD care in primary care and this study could emphasise the gap between evidence and clinical practice. To facilitate implementation of evidence, several actions are needed, such as an improved structure for interprofessional collaboration and patient education, further training for professionals and more resources.

BACKGROUND: Twitter is a free social networking and micro-blogging service that enables its users to read and share information with user and media communities in messages no longer than 140-character. In the year of 2016, there were more than 24 million Indonesian twitter users sharing news, events, as well as personal feelings and experiences on Twitter. This study seeks to validate a search protocol of health related terms using real-time Twitter data which can later be used to understand if, and how, twitter can reveal information on the current health situation in Indonesia. In this validation study of mining protocols, we: 1) extracted geo-located conversations related to health and disease postings on Twitter using a set of pre-defined keywords, 2) assessed the prevalence, frequency and timing of such content in these conversations, and 3) validated how this search protocol was able to detect relevant disease tweets. SUBJECT AND METHODS: Groups of words and phrases relevant to disease symptoms and health outcomes were used in a protocol developed in the Indonesian language in order to extract relevant content from geo-tagged Twitter feeds. A supervised learning algorithm using Classification and Regression Tree´s (CART) was used to validate search protocols of disease and health hits comparing to those identified by a team of human experts. The experts categorized tweets as positive or negative in respect to health events. The model fit was evaluated based on prediction perfor-mance. RESULTS: 390 tweets from historical Twitter feeds and 1,145,649 tweets from Twitter stream feeds during the period July 26th to August 1st, 2016. Only twitter hits with health related keywords in the Indonesian language were obtained. The accuracy of predictions of mined hits versus expert validated hits using the CART algorithm showed good validity with AUC beyond 0.8. CONCLUSION: Monitoring of public sentiment on Twitter, combined with contextual knowledge about the disease, can detect health and disease tweets and potentially be used as a valuable real-time proxy for health events over space and time. Keywords: social networking, disease detection, disease early warning, digital epidemiology, big data analysis

BACKGROUND: Dengue fever remains a major health problem in tropical countries. Some measures had been implemented by the government to control this disease. Apparently, however, these measures were not effective. Therefore, there is a need for a study that provides information to aid the control program. This study aimed at investigating the space-time clustering of dengue fever transmission in Yogyakarta. SUBJECT AND METHODS: This was a retrospective cohort study using surveillance data on dengue fever cases in all subdistricts, Yogyakarta, Indonesia, from January to July 2014. This secondary data was obtained from the Municipality Health Office, Yogyakarta City. The space-time clustering of dengue fever case transmission was analyzed using SaTScan permutation model. RESULT: Dengue fever case transmission was clustered temporarily in several spots during the study period. The clustering of dengue fever transmission differed significantly among sub-districts with Mergangsan sub-district showing the highest cluster (p=0.005). CONCLUSION: There is a significant difference in dengue fever transmission clustering among sub-districts in Yogyakarta City with the highest cluster occurring in Mergangsan sub-district. This finding can be used to guide future study into intervention priority of dengue fever control in Yogyakarta City. Keywords: dengue fever, cluster, space-time analysis, urban, SaTScan

Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are structurally and functionally related and share the same primary receptor, the GM1 ganglioside. Despite their extensive similarities, these two toxins exhibit distinct ligand specificities, with LT being more promiscuous than CT. Here, we have attempted to rationalize the broader binding specificity of LT and the subtle differences between the binding characteristics of LTs from human and porcine origins (mediated by their B subunit pentamers, hLTB and pLTB, respectively). The analysis is based on two crystal structures of pLTB in complexes with the pentasaccharide of its primary ligand, GM1, and with neolactotetraose, the carbohydrate determinant of a typical secondary ligand of LTs, respectively. Important molecular determinants underlying the different binding specificities of LTB and CTB are found to be contributed by Ser95, Tyr18 and Thr4 (or Ser4 of hLTB), which together prestabilize the binding site by positioning Lys91, Glu51 and the adjacent loop region (50–61) containing Ile58 for ligand binding. Glu7 and Ala1 may also play an important role. Many of these residues are closely connected with a recently identified second binding site, and there appears to be cross-talk between the two sites. Binding to N-acetyllactosamine-terminated receptors is further augmented by Arg13 (present in pLT and some hLT variants), as previously predicted.

Climate change has the potential to increase the threat of water-borne diseases, through rises in temperature and sea-level, and precipitation variability. Cholera poses a particular threat, and the need to develop better intervention tools is imminent. Cholera infections are particularly severe for blood group O individuals, who are less protected by the current vaccines. Here we derive a hypothesis as to the molecular origins of blood-group dependence of this disease, based on relevant epidemiological, clinical and molecular data, and give suggestions on how to plan prevention strategies, and develop novel and improved pharmaceuticals.

In a number of bacterial infections, such as Helicobacter pylori, Campylobacter jejuni and Vibrio cholerae infections, a correlation between the severity of disease and blood group phenotype of infected individuals has been observed. In the present investigation, we have studied the molecular basis of this effect for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive bacteria, which act through second messenger pathways to cause diarrhea. It has been suggested that the major virulence factor of ETEC from human isolates, i.e. the human heat-labile enterotoxin (hLT), recognizes certain blood group epitopes, although the molecular basis of blood group antigen recognition is unknown. The 2.5 angstrom crystal structure of the receptor-binding B-subunit of hLT in complex with the blood group A antigen analog GalNAc alpha 3(Fuc alpha-2)Gal beta 4(Fuc alpha-3)Glc beta provides evidence of a previously unknown binding site in the native toxin. The structure reveals the molecular interactions underlying blood group antigen recognition and suggests how this protein can discriminate between different blood group epitopes. These results support the previously debated role of hLT in the blood group dependence of ETEC infections. Similar observations regarding the closely related cholera toxin in V. cholera infections are also discussed. (c) 2007 Elsevier Ltd. All rights reserved.

The aim of this study was to explore nurses' perceptions of climate and environmental issues and examine how nurses perceive their role in contributing to the process of sustainable development.Climate change and its implications for human health represent an increasingly important issue for the healthcare sector. According to the International Council of Nurses Code of Ethics, nurses have a responsibility to be involved and support climate change mitigation and adaptation to protect human health.This is a descriptive, explorative qualitative study.Nurses (n = 18) were recruited from hospitals, primary care and emergency medical services; eight participated in semi-structured, in-depth individual interviews and 10 participated in two focus groups. Data were collected from April-October 2013 in Sweden; interviews were transcribed verbatim and analysed using content analysis.Two main themes were identified from the interviews: (i) an incongruence between climate and environmental issues and nurses' daily work; and (ii) public health work is regarded as a health co-benefit of climate change mitigation. While being green is not the primary task in a lifesaving, hectic and economically challenging context, nurses' perceived their profession as entailing responsibility, opportunities and a sense of individual commitment to influence the environment in a positive direction.This study argues there is a need for increased awareness of issues and methods that are crucial for the healthcare sector to respond to climate change. Efforts to develop interventions should explore how nurses should be able to contribute to the healthcare sector's preparedness for and contributions to sustainable development.

A hybrid between the B subunits of cholera toxin and Escherichia coli heat-labile enterotoxin has been described, which exhibits a novel binding specificity to blood group A and B type 2 determinants. In the present investigation, we have determined the crystal structure of this protein hybrid, termed LCTBK, in complex with the blood group A pentasaccharide GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)GlcNAcbeta, confirming not only the novel binding specificity but also a distinct new oligosaccharide binding site. Binding studies revealed that the new specificity can be ascribed to a single mutation (S4N) introduced into the sequence of Escherichia coli heat-labile enterotoxin. At a resolution of 1.9 A, the new binding site is resolved in excellent detail. Main features include a complex network of water molecules, which is well preserved by the parent toxins, and an unexpectedly modest contribution to binding by the critical residue Asn4, which interacts with the ligand only via a single water molecule.

Lymphedema is a common complication following breast cancer treatment, estimated to affect 20% of breast cancer survivors. The condition is associated with a number of symptoms, such as impaired range of motion and anxiety. A wide range of methods for determining the volume of the lymphedematous arm have been described. Circumference measurement (CM) is commonly used in clinics to appraise arm volume, while water displacement (WD) is often used in studies. The aim of the study was to assess the performance of a new method using 3D-technology in comparison to CM and WD.The study was performed on 25 subjects with lymphedema secondary to breast cancer treatment. Volumetric data from CM, WD, and the 3D-camera were gathered on all subjects. The measurements were performed by two physiotherapists, each subject being measured by one of the physiotherapist. Estimates of differences between the methods was calculated through analyzing the data collected from the three methods using mixed-design analyses of variance. The results indicated a tendency for the 3D-camera to overestimate the volume in comparison the WD by 45.25 mL, 95% confidence interval (CI) -36.31 - 126.82 (p value 0.270). Conversely, CM showed a tendency to underestimate the volume compared to WD (-24.28 mL, CI -99.78 - 51.22, p value 0.521). Thus, no statistically significant difference was found between the methods.The 3D-camera is a viable method for measuring arm volume, performing on level with the established methods WD and CM.

SummaryBackgroundOnly a minority of patients with chronic obstructive pulmonary disease (COPD) have access to pulmonary rehabilitation (PR). Home-based solutions such as telehealthcare, have been used in efforts to make PR more available. The aim of this systematic review was to investigate the effects of telehealthcare on physical activity level, physical capacity and dyspnea in patients with COPD, and to describe the interventions used.MethodsRandomized controlled trials were identified through database searches, reference lists and included authors. Articles were reviewed based on eligibility criteria by three authors. Risk of bias was assessed by two authors. Standardized mean differences (SMD) or mean differences (MD) with 95% CI were calculated. Forest plots were used to present data visually.ResultsNine studies (982 patients) were included. For physical activity level, there was a significant effect favoring telehealthcare (MD, 64.7 min; 95% CI, 54.4–74.9). No difference between groups was found for physical capacity (MD, −1.3 m; 95% CI, −8.1–5.5) and dyspnea (SMD, 0.088; 95% CI, −0.056–0.233). Telehealthcare was promoted through phone calls, websites or mobile phones, often combined with education and/or exercise training. Comparators were ordinary care, exercise training and/or education.ConclusionsThe use of telehealthcare may lead to improvements in physical activity level, although the results should be interpreted with caution given the heterogeneity in studies. This is an important area of research and further studies of the effect of telehealthcare for patients with COPD would be beneficial.RegistrationIn PROSPERO 2012: CRD42012003294. Study protocol: http://www.crd.york.ac.uk/PROSPEROFILES/3294_PROTOCOL_20121016.pdf.

BACKGROUND: The healthcare sector is a significant contributor to global carbon emissions, in part due to extensive travelling by patients and health workers. OBJECTIVES: To evaluate the potential of telemedicine services based on videoconferencing technology to reduce travelling and thus carbon emissions in the healthcare sector. METHODS: A life cycle inventory was performed to evaluate the carbon reduction potential of telemedicine activities beyond a reduction in travel related emissions. The study included two rehabilitation units at Umeå University Hospital in Sweden. Carbon emissions generated during telemedicine appointments were compared with care-as-usual scenarios. Upper and lower bound emissions scenarios were created based on different teleconferencing solutions and thresholds for when telemedicine becomes favorable were estimated. Sensitivity analyses were performed to pinpoint the most important contributors to emissions for different set-ups and use cases. RESULTS: Replacing physical visits with telemedicine appointments resulted in a significant 40-70 times decrease in carbon emissions. Factors such as meeting duration, bandwidth and use rates influence emissions to various extents. According to the lower bound scenario, telemedicine becomes a greener choice at a distance of a few kilometers when the alternative is transport by car. CONCLUSIONS: Telemedicine is a potent carbon reduction strategy in the health sector. But to contribute significantly to climate change mitigation, a paradigm shift might be required where telemedicine is regarded as an essential component of ordinary health care activities and not only considered to be a service to the few who lack access to care due to geography, isolation or other constraints.

Dengue fever is a major problem in many developing countries, including Indonesia. Laboratory examination is used to diagnose dengue infection and to monitor disease progression. Hematology tests, such as platelet count, are also used for timely recognition of the development of severe dengue. In primary health care centers platelet counting is typically performed manually, which is labor intensive and requires an experienced laboratory technician. To address this challenge, we have developed an automatic platelet counter for primary health care and resource-poor settings. The technology is based on a conventional microscope equipped with a digital camera linked to a personal computer, which can capture and analyze microscope images of blood samples. To evaluate the accuracy of the technology, it was compared to platelet counts performed manual by an experienced laboratory technician. Statistical analysis shows no difference between the techniques with a kappa coefficient of 0.6. This method is judged to have great potential as a tool to help primary health centers and other facilities with limited resources to deal with the burden of dengue.

Cholera is a disease which shows a clear blood group profile, with blood group O individuals experiencing the most severe symptoms. For a long time, the cholera toxin has been suspected to be the main culprit of this blood group dependence. Here, we show that both El Tor and classical cholera toxin B-pentamers do indeed bind blood group determinants (with equal affinities), using Surface Plasmon Resonance and NMR spectroscopy. Together with previous structural data, this confirms our earlier hypothesis as to the molecular basis of cholera blood group dependence, with an interesting twist: the shorter blood group H-determinant characteristic of blood group O individuals binds with similar binding affinity compared to the A-determinant, however, with different kinetics.

MOA, a lectin from the mushroom Marasmius oreades, is one of the few reagents that specifically agglutinate blood group B erythrocytes. Further, it is the only lectin known to have exclusive specificity for Galalpha(1,3)Gal-containing sugar epitopes, which are antigens that pose a severe barrier to animal-to-human organ transplantation. We describe here the structure of MOA at 2.4 A resolution, in complex with the linear trisaccharide Galalpha(1,3)Galbeta(1,4)GlcNAc. The structure is dimeric, with two distinct domains per protomer: the N-terminal lectin module adopts a ricinB/beta-trefoil fold and contains three putative carbohydrate-binding sites, while the C-terminal domain serves as a dimerization interface. This latter domain, which has an unknown function, reveals a novel fold with intriguing conservation of an active site cleft. A number of indications suggest that MOA may have an enzymatic function in addition to the sugar-binding properties.

The Marasmius oreades agglutinin (MOA) recognizes blood group B oligosaccharides. This mushroom lectin belongs to the ricin superfamily and is currently the only lectin known with exclusive specificity for Galα1,3Gal-structures, as occur in the subterminally fucosylated blood group B epitope Galα1,3(Fucα1,2)Galβ1,4GlcNAc (MOA's preferred ligand) or without fucosylation in the xenotransplantation epitope. MOA has been co-crystallized with the linear blood group B trisaccharide Galα1,3Galβ1,4GlcNAc using the hanging-drop vapour-diffusion technique at room temperature. MOA crystals were grown in the presence of ammonium formate and HEPES buffer. A 3.0 A data set has been collected. Preliminary analysis of the X-ray data is consistent with space group P3 1 or P3 2 and unit-cell parameters a = b = 105, c = 113 A, with two dimers per asymmetric unit. © 2004 International Union of Crystallography.

A hybrid between the B subunits of cholera toxin and Escherichia coli heat-labile enterotoxin has been described, which exhibits a novel binding specificity to blood group A and B type 2 determinants. In the present investigation, we have determined the crystal structure of this protein hybrid, termed LCTBK, in complex with the blood group A pentasaccharide GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)GlcNAcbeta, confirming not only the novel binding specificity but also a distinct new oligosaccharide binding site. Binding studies revealed that the new specificity can be ascribed to a single mutation (S4N) introduced into the sequence of Escherichia coli heat-labile enterotoxin. At a resolution of 1.9 A, the new binding site is resolved in excellent detail. Main features include a complex network of water molecules, which is well preserved by the parent toxins, and an unexpectedly modest contribution to binding by the critical residue Asn4, which interacts with the ligand only via a single water molecule.