Åsa Holmner

Molecular basis of cholera blood-group dependence and implications for a world characterized by climate change.

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.

Crystal Structures Exploring the Origins of the Broader Specificity of Escherichia coli Heat-Labile Enterotoxin Compared to Cholera Toxin

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.

Both El Tor and classical cholera toxin bind blood group determinants

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.

Prediction of Dengue Outbreaks Based on Disease Surveillance and Meteorological Data

Research is needed to create early warnings of dengue outbreaks to inform stakeholders and control the disease. This analysis composes of a comparative set of prediction models including only meteorological variables; only lag variables of disease surveillance; as well as combinations of meteorological and lag disease surveillance variables. Generalized linear regression models were used to fit relationships between the predictor variables and the dengue surveillance data as outcome variable on the basis of data from 2001 to 2010. Data from 2011 to 2013 were used for external validation purposed of prediction accuracy of the model. Model fit were evaluated based on prediction performance in terms of detecting epidemics, and for number of predicted cases according to RMSE and SRMSE, as well as AIC. An optimal combination of meteorology and autoregressive lag terms of dengue counts in the past were identified best in predicting dengue incidence and the occurrence of dengue epidemics. Past data on disease surveillance, as predictor alone, visually gave reasonably accurate results for outbreak periods, but not for non-outbreaks periods. A combination of surveillance and meteorological data including lag patterns up to a few years in the past showed most predictive of dengue incidence and occurrence in Yogyakarta, Indonesia. The external validation showed poorer results than the internal validation, but still showed skill in detecting outbreaks up to two months ahead. Prior studies support the fact that past meteorology and surveillance data can be predictive of dengue. However, to a less extent has prior research shown how the longer-term past disease incidence data, up to years, can play a role in predicting outbreaks in the coming years, possibly indicating cross-immunity status of the population.

Carbon footprint of telemedicine solutions--unexplored opportunity for reducing carbon emissions in the health sector.

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.

Climate change and eHealth : a promising strategy for health sector mitigation and adaptation

Climate change is one of todays most pressing global issues. Policies to guide mitigation and adaptation are needed to avoid the devastating impacts of climate change. The health sector is a significant contributor to greenhouse gas emissions in developed countries, and its climate impact in low-income countries is growing steadily. This paper reviews and discusses the literature regarding health sector mitigation potential, known and hypothetical co-benefits, and the potential of health information technology, such as eHealth, in climate change mitigation and adaptation. The promising role of eHealth as an adaptation strategy to reduce societal vulnerability to climate change, and the links between mitigation and adaptation, are also discussed. The topic of environmental eHealth has gained little attention to date, despite its potential to contribute to more sustainable and green health care. A growing number of local and global initiatives on ‘green information and communication technology (ICT)’ are now mentioning eHealth as a promising technology with the potential to reduce emission rates from ICT use. However, the embracing of eHealth is slow because of limitations in technological infrastructure, capacity and political will. Further research on potential emissions reductions and co-benefits with green ICT, in terms of health outcomes and economic effectiveness, would be valuable to guide development and implementation of eHealth in health sector mitigation and adaptation policies.

Crystallization and preliminary X-ray crystallographic studies of a lectin from the mushroom Marasmius oreades.

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 Galalpha1,3Gal-structures, as occur in the subterminally fucosylated blood group B epitope Galalpha1,3(Fucalpha1,2)Galbeta1,4GlcNAc (MOAs preferred ligand) or without fucosylation in the xenotransplantation epitope. MOA has been co-crystallized with the linear blood group B trisaccharide Galalpha1,3Galbeta1,4GlcNAc 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.

Usefulness and Relevance of an eHealth Tool in Supporting the Self-Management of Chronic Obstructive Pulmonary Disease: Explorative Qualitative Study of a Cocreative Process

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.

Automatic platelets counter for supporting dengue case detection in primary health care in indonesia.

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.