Comparing healthcare needs by language: interpreted Arabic and Somali telehealth calls in two regions of Sweden, 2014-18.

BACKGROUND: Limited language fluency can impede healthcare system navigation. In Sweden, the national telehealth line (Healthcare Guide 1177) offers interpretation in Arabic and Somali. We compared calls by language to identify differences in healthcare use for immigrant populations, focusing on three contact causes: pregnancy; vomiting or nausea in children; and worry/anxiety. METHODS: We conducted a cross-sectional analysis of 3.9 million (n = 18 351 Arabic, n = 7199 Somali) telehealth calls (2014-18). Using multivariable logistic regression, we investigated associations between language of the call (Arabic, Somali, non-interpreted) and each contact cause. Potential confounders (age, region, year, and additionally for vomiting or nausea, month) and an interaction between age and language were considered. RESULTS: Compared with non-interpreted calls, interpreted calls were associated with increased odds of being for pregnancy, especially for 19 to 29-year-olds [adjusted odds ratio (aOR) (95% CI) = 4.04 (3.66-4.46) and 4.60 (4.05-5.23), for Arabic and Somali calls, respectively]. Vomiting or nausea showed similar results, with aOR increasing with age: from 0.90 (0.75-1.07) (Arabic, <1 year) to 3.79 (2.86-5.01) (Somali, 5-9 years). In contrast, in unadjusted analyses, Arabic and Somali calls were associated with decreased odds of being for worry/anxiety [OR = 0.47 (0.38-0.58) and 0.34 (0.21-0.50)], respectively, compared with non-interpreted calls. CONCLUSION: Our results suggest callers to the interpreted lines may need additional assistance navigating the healthcare system for pregnancy and for vomiting or nausea among children. These findings can inform healthcare services planning for immigrants to Sweden and highlight a novel use of telehealth data as a way to uncover disparities in healthcare use within a multi-linguistic population.

Early outbreak detection by linking health advice line calls to water distribution areas retrospectively demonstrated in a large waterborne outbreak of cryptosporidiosis in Sweden.

BACKGROUND: In the winter and spring of 2011 a large outbreak of cryptosporidiosis occurred in Skellefteå municipality, Sweden. This study summarizes the outbreak investigation in terms of outbreak size, duration, clinical characteristics, possible source(s) and the potential for earlier detection using calls to a health advice line. METHODS: The investigation included two epidemiological questionnaires and microbial analysis of samples from patients, water and other environmental sources. In addition, a retrospective study based on phone calls to a health advice line was performed by comparing patterns of phone calls between different water distribution areas. RESULTS: Our analyses showed that approximately 18,500 individuals were affected by a waterborne outbreak of cryptosporidiosis in Skellefteå in 2011. This makes it the second largest outbreak of cryptosporidiosis in Europe to date. Cryptosporidium hominis oocysts of subtype IbA10G2 were found in patient and sewage samples, but not in raw water or in drinking water, and the initial contamination source could not be determined. The outbreak went unnoticed to authorities for several months. The analysis of the calls to the health advice line provides strong indications early in the outbreak that it was linked to a particular water treatment plant. CONCLUSIONS: We conclude that an earlier detection of the outbreak by linking calls to a health advice line to water distribution areas could have limited the outbreak substantially.

Tracking a complete voltage-sensor cycle with metal-ion bridges.

Voltage-gated ion channels open and close in response to changes in membrane potential, thereby enabling electrical signaling in excitable cells. The voltage sensitivity is conferred through four voltage-sensor domains (VSDs) where positively charged residues in the fourth transmembrane segment (S4) sense the potential. While an open state is known from the Kv1.2/2.1 X-ray structure, the conformational changes underlying voltage sensing have not been resolved. We present 20 additional interactions in one open and four different closed conformations based on metal-ion bridges between all four segments of the VSD in the voltage-gated Shaker K channel. A subset of the experimental constraints was used to generate Rosetta models of the conformations that were subjected to molecular simulation and tested against the remaining constraints. This achieves a detailed model of intermediate conformations during VSD gating. The results provide molecular insight into the transition, suggesting that S4 slides at least 12 Å along its axis to open the channel with a 3(10) helix region present that moves in sequence in S4 in order to occupy the same position in space opposite F290 from open through the three first closed states.

GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit.

MOTIVATION: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. RESULTS: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. AVAILABILITY: GROMACS is an open source and free software available from http://www.gromacs.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

310-helix conformation facilitates the transition of a voltage sensor S4 segment toward the down state.

The activation of voltage-gated ion channels is controlled by the S4 helix, with arginines every third residue. The x-ray structures are believed to reflect an open-inactivated state, and models propose combinations of translation, rotation, and tilt to reach the resting state. Recently, experiments and simulations have independently observed occurrence of 3(10)-helix in S4. This suggests S4 might make a transition from α- to 3(10)-helix in the gating process. Here, we show 3(10)-helix structure between Q1 and R3 in the S4 segment of a voltage sensor appears to facilitate the early stage of the motion toward a down state. We use multiple microsecond-steered molecular simulations to calculate the work required for translating S4 both as α-helix and transformed to 3(10)-helix. The barrier appears to be caused by salt-bridge reformation simultaneous to R4 passing the F233 hydrophobic lock, and it is almost a factor-two lower with 3(10)-helix. The latter facilitates translation because R2/R3 line up to face E183/E226, which reduces the requirement to rotate S4. This is also reflected in a lower root mean-square deviation distortion of the rest of the voltage sensor. This supports the 3(10) hypothesis, and could explain some of the differences between the open-inactivated- versus activated-states.

Molecular dynamics simulation of the antiamoebin ion channel: linking structure and conductance.

Molecular-dynamics simulations were carried out to ascertain which of the potential multimeric forms of the transmembrane peptaibol channel, antiamoebin, is consistent with its measured conductance. Estimates of the conductance obtained through counting ions that cross the channel and by solving the Nernst-Planck equation yield consistent results, indicating that the motion of ions inside the channel can be satisfactorily described as diffusive. The calculated conductance of octameric channels is markedly higher than the conductance measured in single channel recordings, whereas the tetramer appears to be nonconducting. The conductance of the hexamer was estimated to be 115 ± 34 pS and 74 ± 20 pS, at 150 mV and 75 mV, respectively, in satisfactory agreement with the value of 90 pS measured at 75 mV. On this basis, we propose that the antiamoebin channel consists of six monomers. Its pore is large enough to accommodate K⁺ and Cl⁻ with their first solvation shells intact. The free energy barrier encountered by K⁺ is only 2.2 kcal/mol whereas Cl⁻ encounters a substantially higher barrier of nearly 5 kcal/mol. This difference makes the channel selective for cations. Ion crossing events are shown to be uncorrelated and follow Poisson statistics.

Membrane proteins diffuse as dynamic complexes with lipids.

We describe how membrane proteins diffuse laterally in the membrane plane together with the lipids surrounding them. We find a number of intriguing phenomena. The lateral displacements of the protein and the lipids are strongly correlated, as the protein and the neighboring lipids form a dynamical protein-lipid complex, consisting of approximately 50-100 lipids. The diffusion of the lipids in the complex is much slower compared to the rest of the lipids. We also find a strong directional correlation between the movements of the protein and the lipids in its vicinity. The results imply that in crowded membrane environments there are no "free" lipids, as they are all influenced by the protein structure and dynamics. Our results indicate that, in studies of cell membranes, protein and lipid dynamics have to be considered together.

Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel.

Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120 degrees rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation ( approximately 35 degrees ) of the extracellular end of all S4 segments is present also in a reference 0.5 micros simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 3(10) helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4-lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations.

Investigating novel approaches to tick-borne encephalitis surveillance in Sweden, 2010-2017.

Tick-borne encephalitis (TBE) is a vaccine-preventable, high-priority disease in Sweden, with increasing incidence. However, surveillance is limited to case reports. We investigated relationships between reported TBE incidence and syndromic surveillance data to determine if these novel data sources could provide earlier indications of disease activity. We retrospectively compared national, weekly (2010-2017) reported TBE incidence to the percentage of TBE-related a) searches on the main Swedish healthcare information website and b) calls to its telehealth service using Spearman's ρ to determine the most strongly correlated lags. We conducted a sub-analysis (2012-2017) of TBE-related Google Trends queries and compared the number of TBE-related media stories to each novel surveillance dataset. Healthcare website searches for "tbe" and "vaccine" combined, "tbe", "tick", and "tick bite" led case data by 12, 8, 7, and 6 weeks, respectively (ρ = 0.87-0.89); telehealth calls led by 4 weeks (ρ = 0.92; all p < 0.001). Correlations and lags for Google Trends and healthcare website searches were fairly similar to each other. In comparison, correlation between the different syndromic surveillance datasets and the number of media stories was lower (ρ = 0.25-0.56). We observed volume discrepancies between TBE incidence and the novel surveillance datasets during some years, particularly for web searches. Syndromic surveillance data were strongly correlated with and preceded case data by 4-12 weeks. Syndromic data may provide advanced awareness and earlier indications of TBE activity, which can improve timing and specificity of public health communications. The use of these data as supplements to notifiable disease data for national planning and preparedness in real-time should be investigated.

[High mortality during the 2018 heatwave in Sweden]. / Ovanligt många dödsfall i Sverige sommaren 2018 - Drygt 600 kan ha dött till följd av värmeböljan.

During the summer of 2018 large parts of Sweden experienced a record-breaking heatwave regarding temperatures and duration. Previous studies from Sweden with less extreme heat have shown that daily mortality is expected to increase during periods with high temperatures.  Between the 2nd of July and 5th of August, the period in 2018 with the highest temperatures, 635 more deaths were observed in Sweden compared to the same period in 2017. This corresponds to an 8,2% increase over the entire heatwave, and a 13,5% increase during the warmest week, the 16th to 22nd of July.  When using temperature data from four weather stations and relative risks from the models established for the Swedish heatwave early warning system, the heat episode in the summer of 2018 could be expected to result in 601-746 excess deaths, depending on model choice. Comparison with the observed mortality data therefore confirm the ability of the risk models to predict the expected increase in mortality also during longer periods with higher temperatures than ever studied before in Sweden.

Two outbreaks of cryptosporidiosis associated with cattle spring pasture events.

Over a period of less than four weeks, 50 human cases of cryptosporidiosis were reported from a relatively small geographical area in Sweden. All cases were associated with visits to cattle spring pasture events at two farms (referred to as Farm A and B). Epidemiological and microbiological evidence show that contact with calves at the farms was the most likely source of Cryptosporidium infections. Gp60 sequences from human and calf isolates at Farm A were identical to each other, but differed from those at Farm B where, again, human and calf gp60 sequences were identical, proving that the two outbreaks had no common origin. As a direct consequence of these two outbreaks, and guided by knowledge gained from the outbreak investigations, the Swedish Board of Agriculture and all relevant farmer advisory organizations have updated their hygiene instructions for farm visits.

Implementation of the CHARMM Force Field in GROMACS: Analysis of Protein Stability Effects from Correction Maps, Virtual Interaction Sites, and Water Models.

CHARMM27 is a widespread and popular force field for biomolecular simulation, and several recent algorithms such as implicit solvent models have been developed specifically for it. We have here implemented the CHARMM force field and all necessary extended functional forms in the GROMACS molecular simulation package, to make CHARMM-specific features available and to test them in combination with techniques for extended time steps, to make all major force fields available for comparison studies in GROMACS, and to test various solvent model optimizations, in particular the effect of Lennard-Jones interactions on hydrogens. The implementation has full support both for CHARMM-specific features such as multiple potentials over the same dihedral angle and the grid-based energy correction map on the ϕ, ψ protein backbone dihedrals, as well as all GROMACS features such as virtual hydrogen interaction sites that enable 5 fs time steps. The medium-to-long time effects of both the correction maps and virtual sites have been tested by performing a series of 100 ns simulations using different models for water representation, including comparisons between CHARMM and traditional TIP3P. Including the correction maps improves sampling of near native-state conformations in our systems, and to some extent it is even able to refine distorted protein conformations. Finally, we show that this accuracy is largely maintained with a new implicit solvent implementation that works with virtual interaction sites, which enables performance in excess of 250 ns/day for a 900-atom protein on a quad-core desktop computer.

Protein evolutionary rates correlate with expression independently of synonymous substitutions in Helicobacter pylori.

In free-living microorganisms, such as Escherichia coli and Saccharomyces cerevisiae, both synonymous and nonsynonymous substitution frequencies correlate with expression levels. Here, we have tested the hypothesis that the correlation between amino acid substitution rates and expression is a by-product of selection for codon bias and translational efficiency in highly expressed genes. To this end, we have examined the correlation between protein evolutionary rates and expression in the human gastric pathogen Helicobacter pylori, where the absence of selection on synonymous sites enables the two types of substitutions to be uncoupled. The results revealed a statistically significant negative correlation between expression levels and nonsynonymous substitutions in both H. pylori and E. coli. We also found that neighboring genes located on the same, but not on opposite strands, evolve at significantly more similar rates than random gene pairs, as expected by co-expression of genes located in the same operon. However, the two species differ in that synonymous substitutions show a strand-specific pattern in E. coli, whereas the weak similarity in synonymous substitutions for neighbors in H. pylori is independent of gene orientation. These results suggest a direct influence of expression levels on nonsynonymous substitution frequencies independent of codon bias and selective constraints on synonymous sites.