Relational continuity may give better clinical outcomes in patients with serious mental illness - a systematic review.

BACKGROUND: Continuity of care is considered important for results of treatment of serious mental illness (SMI). Yet, evidence of associations between relational continuity and different medical and social outcomes is sparse. Research approaches differ considerably regarding how to best assess continuity as well as which outcome to study. It has hitherto been difficult to evaluate the importance of relational continuity of care. The aim of this systematic review was to investigate treatment outcomes, including effects on resource use and costs associated with receiving higher relational continuity of care for patients with SMI. METHODS: Eleven databases were searched between January 2000 and February 2021 for studies investigating associations between some measure of relational continuity and health outcomes and costs. All eligible studies were assessed for study relevance and risk of bias by at least two independent reviewers. Only studies with acceptable risk of bias were included. Due to study heterogeneity the synthesis was made narratively, without meta-analysis. The certainty of the summarized result was assessed using GRADE. Study registration number in PROSPERO: CRD42020196518. RESULTS: We identified 8 916 unique references and included 17 studies comprising around 300 000 patients in the review. The results were described with regard to seven outcomes. The results indicated that higher relational continuity of care for patients with serious mental illness may prevent premature deaths and suicide, may lower the number of emergency department (ED) visits and may contribute to a better quality of life compared to patients receiving lower levels of relational continuity of care. The certainty of the evidence was assessed as low or very low for all outcomes. The certainty of results for the outcomes hospitalization, costs, symptoms and functioning, and adherence to drug treatment was very low with the result that no reliable conclusions could be drawn in these areas. CONCLUSIONS: The results of this systematic review indicate that having higher relational continuity of care may have beneficial effects for patients with severe mental illness, and no results have indicated the opposite relationship. There is a need for better studies using clear and distinctive measures of exposure for relational continuity of care.

Different antibiotic regimes in men diagnosed with lower urinary tract infection - a retrospective register-based study.

OBJECTIVE: To compare the proportion of therapy failure, recurrence and complications within 30 days after consultation between men diagnosed with lower urinary tract infection (UTI) treated with narrow-spectrum antibiotics (nitrofurantoin or pivmecillinam) and broad-spectrum antibiotics (fluoroquinolones or trimethoprim or trimethoprim/sulfamethoxazole). DESIGN: A retrospective cohort study based on data derived from electronic medical records between January 2012 and December 2015. SETTING: Primary health care and hospital care in five different counties in Sweden. Patients: A total of 16,555 men aged between 18 and 79 years diagnosed with lower UTI. MAIN OUTCOME MEASURES: Treatment with narrow-spectrum antibiotics was compared with broad-spectrum antibiotics regarding therapy failure, recurrence and complications within 30 days. RESULTS: The median age of included men was 65 IQR (51-72) years. Narrow-spectrum antibiotics were prescribed in 8457 (40%) and broad-spectrum antibiotics in 12,667 (60%) cases, respectively. Therapy failure was registered in 192 (0.9%), recurrence in 1277 (6%) and complications in 121 (0.6%) cases. Therapy failure and recurrence were more common in patients treated with narrow-spectrum antibiotics and trimethoprim (p < 0.001), but no such difference could be detected regarding complications. CONCLUSION: There was no difference in incidence of complications within 30 days between men treated with narrow- or broad-spectrum antibiotics. Patients prescribed broad-spectrum antibiotics had lower odds of reconsultation because of therapy failure and recurrence. From current data, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men with lower UTI. KEY POINTS Complications such as pyelonephritis and sepsis are uncommon in men diagnosed with lower urinary tract infection treated with antibiotics. There was no difference in incidence of complications among men diagnosed with lower urinary tract infection treated with narrow- or broad-spectrum antibiotics. In spite of higher incidence of therapy failure and recurrence, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men diagnosed with lower UTI.

Antibiotic prescribing in relation to diagnoses and consultation rates in Belgium, the Netherlands and Sweden: use of European quality indicators.

OBJECTIVE: To assess the quality of antibiotic prescribing in primary care in Belgium, the Netherlands and Sweden using European disease-specific antibiotic prescribing quality indicators (APQI) and taking into account the threshold to consult and national guidelines. DESIGN: A retrospective observational database study. SETTING: Routine primary health care registration networks in Belgium, the Netherlands and Sweden. SUBJECTS: All consultations for one of seven acute infections [upper respiratory tract infection (URTI), sinusitis, tonsillitis, otitis media, bronchitis, pneumonia and cystitis] and the antibiotic prescriptions in 2012 corresponding to these diagnoses. MAIN OUTCOME MEASURES: Consultation incidences for these diagnoses and APQI values (a) the percentages of patients receiving an antibiotic per diagnosis, (b) the percentages prescribed first-choice antibiotics and (c) the percentages prescribed quinolones. RESULTS: The consultation incidence for respiratory tract infection was much higher in Belgium than in the Netherlands and Sweden. Most of the prescribing percentage indicators (a) were outside the recommended ranges, with Belgium deviating the most for URTI and bronchitis, Sweden for tonsillitis and the Netherlands for cystitis. The Netherlands and Sweden prescribed the recommended antibiotics (b) to a higher degree and the prescribing of quinolones exceeded the proposed range for most diagnoses (c) in Belgium. The interpretation of APQI was found to be dependent on the consultation incidences. High consultation incidences were associated with high antibiotic prescription rates. Taking into account the recommended treatments from national guidelines improved the results of the APQI values for sinusitis in the Netherlands and cystitis in Sweden. CONCLUSION: Quality assessment using European disease-specific APQI was feasible and their inter-country comparison can identify opportunities for quality improvement. Their interpretation, however, should take consultation incidences and national guidelines into account. Differences in registration quality might limit the comparison of diagnosis-linked data between countries, especially for conditions such as cystitis where patients do not always see a clinician before treatment. Key points The large variation in antibiotic use between European countries points towards quality differences in prescribing in primary care. • The European disease-specific antibiotic prescribing quality indicators (APQI) provide insight into antibiotic prescribing, but need further development, taking into account consultation incidences and country-specific guidelines. • The incidence of consultations for respiratory tract infections was almost twice as high in Belgium compared to the Netherlands and Sweden. • Comparison between countries of diagnosis-linked data were complicated by differences in data collection, especially for urinary tract infections.

Reduction in antibiotic prescribing for respiratory tract infections in Swedish primary care- a retrospective study of electronic patient records.

BACKGROUND: Swedish studies on antibiotic use in primary care have been based on one-week registrations of infections. In order to study adherence to guidelines, analyses based on large databases that provide information on diagnosis linked prescriptions, are needed. This study describes trends in management of infections in Swedish primary care particularly with regards to antibiotic prescribing and adherence to national guidelines. METHODS: A descriptive study of Sweden's largest database regarding diagnosis linked antibiotic prescription data, the Primary care Record of Infections in Sweden (PRIS), for the years 2008, 2010 and 2013. RESULTS: Although the consultation rate for all infections remained around 30% each year, antibiotic prescribing rates decreased significantly over the years from 53.7% in 2008, to 45.5% in 2010, to 38.6% in 2013 (p = .032). The antibiotic prescribing rate for respiratory tract infections (RTIs) decreased from 40.5% in 2008 to 24.9% in 2013 while those for urinary tract infections and skin and soft tissue infections were unchanged. For most RTI diagnoses there was a decrease in prescription rate from 2008 to 2013, particularly for the age group 0-6 years. Phenoxymethylpenicillin (PcV) was the antibiotic most often prescribed, followed by tetracycline. Tonsillitis and acute otitis media were the two RTI diagnoses with the highest number of prescriptions per 1000 patient years (PY). For these diagnoses an increase in adherence to national guidelines was seen, with regards to treatment frequency, choice of antibiotics and use of rapid antigen detection test. The frequency in antibiotic prescribing varied greatly between different Primary Healthcare Centres (PHCCs). CONCLUSION: Falling numbers of consultations and decreased antibiotic prescription rates for RTIs have reduced the antibiotic use in Swedish primary care substantially. Overprescribing of antibiotics could still be suspected due to large variability in prescribing frequency, especially for acute bronchitis and sinusitis. Continuous evaluation of diagnosis linked prescribing data and feedback to doctors is essential in order to achieve a more prudent antibiotic use.

Cubic and sponge phases in ether lipid-solvent-water ternary systems: phase behavior and NMR characterization.

The phase behavior of 1-glyceryl monoleyl ether (GME) in mixtures of water and the solvents 1,5-pentanediol (POL) or N-methyl-2-pyrrolidone (NMP) was investigated by ocular inspection, polarization microscopy, and small-angle X-ray diffraction (SAXD). Phase diagrams were constructed based on analyses of more than 200 samples prepared using the two different solvents at 20 °C. The inverse hexagonal phase formed by GME in excess of water was transformed into the cubic and sponge phase with the increasing amount of each solvent. Particularly POL allowed for the formation of an extended sponge phase area in the phase diagram, comprising up to 70% POL-water mixture. The phase behavior using NMP was found to be similar to the earlier investigated solvent propylene glycol. The extended sponge phase for the POL system was attributed to POLs strong surface/interfacial activity with the potential to stabilize the polar/apolar interface of the sponge phase. The cubic and sponge phases formed using POL were further studied by NMR in order to measure the partitioning of POL between the lipid and aqueous domains of the phases. The domain partition coefficient K (lipid domain/aqueous domain) for POL in cubic and sponge phases was found to be 0.78 ± 0.14 and constant for the two phases.

Factors influencing the prescription of drugs of different price levels.

PURPOSE: Socioeconomic factors have been suggested to influence the prescribing of newer and more expensive drugs. In the present study, individual and health care provider factors were studied in relation to the prevalence of differently priced drugs. METHODS: Register data for dispensed drugs were retrieved for 18 486 individuals in a county council in Sweden. The prevalence of dispensed drugs was combined with data for the individual's gender, age, education, income, foreign background, and type of caregiver. For each of the diagnostic groups (chronic obstructive pulmonary disease [COPD], depression, diabetes, and osteoporosis), selected drugs were dichotomized into cost categories, lower and higher price levels. Univariate and multivariate logistic regressions were performed using cost category as the dependent variable and the individual and provider factors as independent variables. RESULTS: In all four diagnostic groups, differences were observed in the prescription of drugs of lower and higher price levels with regard to the different factors studied. Age and gender affected the prescription of drugs of lower and higher price levels more generally, except for gender in the osteoporosis group. Income, education, foreign background, and type of caregiver affected prescribing patterns but in different ways for the different diagnostic groups. CONCLUSIONS: Certain individual and provider factors appear to influence the prescribing of drugs of different price levels. Because the average price for the cheaper drugs versus more costly drugs in each diagnostic group was between 19% and 69%, there is a risk that factors other than medical needs are influencing the choice of drug.

Outcomes associated with higher relational continuity in the treatment of persons with asthma or chronic obstructive pulmonary disease: A systematic review.

Background: Asthma and chronic obstructive pulmonary disease (COPD) are chronic conditions where relational continuity of care, as in regularly meeting the same health care provider, creates opportunities for monitoring and adjustment of treatment based on an individual's changing needs, potentially affecting quality of delivered care. The aim of this systematic review was to investigate the effects of relational continuity in the treatment of persons with asthma or COPD. Methods: Eleven databases (CINAHL, Medline, PsycINFO, Scopus, Embase, Cochrane Library, Database of Systematic Review of Effects, DARE, Epistemonikos, NICE Evidence Search, KSR Evidence and AHRQ) were searched between January 1, 2000, and February 1 - 4, 2021, for controlled and observational studies about relational continuity and health outcomes for persons with asthma and/or COPD. Inclusion criteria were studies investigating an index or aspect relevant to relational continuity between a health professional/team of health professionals and patients. After screening, and assessment of study relevance and quality by at least two independent reviewers, studies with acceptable risk of bias were included and summary data was extracted from the publications. Main outcomes were mortality, morbidity (including health care utilization) and cost measures. Syntheses without metanalyses were performed due to considerable study heterogeneity. The certainty of the summarized result was assessed using GRADE (the Grading of Recommendations Assessment, Development and Evaluation). PROSPERO study registration number: CRD42020196518. Findings: We identified 2824 unique references and included 15 studies (14 observational and 1 randomized controlled trial) in the review, from which results were derived for six outcomes. For persons with asthma or COPD we found that higher compared to lower relational continuity of care prevents premature mortality (low certainty; 2 studies, 111 545 participants), lowers risk of emergency department visits (low certainty, 5 studies, 362 305 participates) and risk of hospitalization (moderate certainty, 9 studies, 525 716 participants), and lowers health care costs (low certainty; 4 studies, 390 682 participants). Results regarding treatment adherence (1 study, 971 participants) and patient perceptions (3 studies, 2026 participants) were assessed as having very low certainty. Interpretation: Low to moderate certainty evidence suggests that higher versus lower relational continuity of care for persons with asthma or COPD prevents premature mortality, lowers risks of unplanned health care utilization and reduces health care costs. The results may be of value when planning care for individuals and for policymakers in organizing health care and developing guidelines for treatment and follow-up routines. Funding: None.

[How do we want to organize health centres? 838 Swedish general practitioners' attitudes to a personal patient list]. / Så vill vi organisera vårdcentraler.

In Swedish primary care patients are registered at health centres where different professions, such as general practitioners (GPs), nurses, assistant nurses, counsellors, physiotherapists, psychologists and biomedical analysts, work. In an international comparison personal physician continuity is low in Sweden. Several governmental inquiries propose that patients register with one GP or a care team. Do Swedish GPs want a personal patient list and how should this best be realised? A web survey was distributed to the members of the Swedish Union of General Practitioners and was answered by 838 GPs. 91% wanted a personal patient list if reasonably sized, the option to limit their list, and shared responsibility for the list with colleagues or a team. To be able to plan the working day themselves and designated time for collegial dialogue was considered essential for increased efficiency, well-being and reduced risk of patients harm due to their doctor's knowledge gaps.

A lipidic-sponge phase screen for membrane protein crystallization.

A major current deficit in structural biology is the lack of high-resolution structures of eukaryotic membrane proteins, many of which are key drug targets for the treatment of disease. Numerous eukaryotic membrane proteins require specific lipids for their stability and activity, and efforts to crystallize and solve the structures of membrane proteins that do not address the issue of lipids frequently end in failure rather than success. To help address this problem, we have developed a sparse matrix crystallization screen consisting of 48 lipidic-sponge phase conditions. Sponge phases form liquid lipid bilayer environments which are suitable for conventional hanging- and sitting-drop crystallization experiments. Using the sponge phase screen, we obtained crystals of several different membrane proteins from bacterial and eukaryotic sources. We also demonstrate how the screen may be manipulated by incorporating specific lipids such as cholesterol; this modification led to crystals being recovered from a bacterial photosynthetic core complex.

Trends in number of consultations and antibiotic prescriptions for respiratory tract infections between 1999 and 2005 in primary healthcare in Kalmar County, Southern Sweden.

UNLABELLED: BACKGROUND. Respiratory tract infections (RTIs) comprise the most common indication for consulting a general practitioner and obtaining an antibiotic prescription. OBJECTIVE: To study changes in the number of visits, diagnoses, and antibiotic prescriptions for RTI in primary healthcare during the period 1999-2005. DESIGN: A retrospective, descriptive, population-based study of electronic patient records. Setting. County of Kalmar in southeastern Sweden. PATIENTS: Patients visiting primary healthcare units in Kalmar County for an RTI between 1 July 1999 and 31 December 2005. MAIN OUTCOME MEASURES: RTI diagnoses, antibiotic prescriptions, age groups. RESULTS: A total of 240 447 visits for RTI made between 1999 and 2005 were analysed. The yearly consultation rates for the diagnoses acute tonsillitis and AOM decreased by 12% and 10%, respectively (p = 0.001). Of all patients consulting for an RTI diagnosis, 45% received antibiotics. Of all prescribed antibiotics, 60% were for phenoxymethylpenicillin (PcV) and 18% doxycycline. Amoxicillin or amoxicillin + clavulanic acid was prescribed to a lesser extent. The proportion of patients obtaining an antibiotic prescription was almost constant over time (44-46%). The prescriptions of doxycycline showed increasing values (NS). The prescriptions of remaining antibiotics decreased significantly especially for patients up to middle age. CONCLUSION: This large population study, comprising more than six years of observations, showed the number of primary healthcare patients receiving an RTI diagnosis decreased during the period 1999-2005, but the proportion of patients receiving an antibiotic prescription remained the same. The large seasonal variations indicate a need for further interventions to decrease antibiotic use for RTIs.

[The doctor's personal knowledge of patients saved resources and reduced mortality in an American study. How should a care system in Sweden be designed to get similar effects?] / Läkares personkännedom sparade liv och resurser - Personlig kontinuitet viktig i ett nytt svenskt vårdsystem.

In a recent study of more than 500 000 hospitalisations, doctors with personal knowledge of their patients used less resources, more often discharged them to their own home and their patients had lower mortality. Furthermore, other studies have shown that personal continuity increases patient satisfaction as well as compliance and reduces costs for medical services and visits to emergency services. In a Swedish context we discuss how a combination of organizational factors and personal listing on physicians and continuity of care favour personal knowledge between physician and patient and contribute to a primary care that works well for both the frail elderly and the healthy young.

[Personal physician continuity in primary care associated with fewer emergency room visits]. / Hög personlig läkar­kontinuitet i primärvård förenad med färre besök på akutmottagning - En populationsbaserad studie i Jönköpings sjukvårdsregion.

Overloading of the emergency departments in hospitals is, in Sweden, a common problem that is often blamed on lack of access to primary care.  We have conducted a cross-sectional study comprising more than 40% of the 347 837  inhabitants of Region Jönköping with access to complete individual data on healthcare consumption, personal doctor continuity, socio-economics, and accessibility data for all of the region's health centres. Individuals with high personal continuity at their own health centre had significantly fewer emergency room visits compared to those with the lowest continuity: for younger adults 55% and for elderly 34% fewer emergency room visits. Access to doctor consultations or to counselling nurses in primary care was not associated with a lower number of emergency room visits. Our results show the importance of personal doctor continuity also for the group of younger adults.

Structure and dynamics of a sponge phase in the methyl delta-aminolevulinate/monoolein/water/propylene glycol system.

The structural effect caused by the addition of up to 16% (w/w) of the hydrochloride salt of delta-aminolevulinic acid (ALA, HOOC-CH2-CH2-CO-CH2-NH2HCl) or its methyl ester (m-ALA) to the sponge phase formed of monoolein/water/propylene glycol was investigated by means of crossed polarizers, small angle X-ray diffraction (SAXD) and nuclear magnetic resonance diffusometry (NMRD). Inspection with crossed polarizers revealed that additions of 4-16% (w/w) m-ALA transformed the isotropic bicontinuous sponge phase partly (4-10%) or completely (13 and 16%) into an anisotropic lamellar phase, indicating that m-ALA has a flattening effect on the bilayer curvature. The addition of 16% (w/w) ALA did not show any effect on the sponge phase. By addition of water to the anisotropic m-ALA samples, isotropic liquids were re-formed. The SAXD data for the isotropic liquids showed a diffuse Bragg peak and the NMRD self-diffusion coefficients for the drug (m-ALA) and the components of the original sponge phase (monoolein, water and propylene glycol) were shown to be essentially constant for 0-16% (w/w) added m-ALA. These results confirmed the hypothesis that the re-formed isotropic phases were indeed sponge phases. Water, for example, showed a diffusion coefficient of 3.1-3.9x10(-10)m(2)s(-1) in the sponge phase, compared to 5.3-5.7 x 10(-10)m2s(-1) in relevant water/propylene glycol solutions or 2.3 x 10(-9)m2s(-1) in pure water. The reduction can be explained as a consequence of the microstructure (congruent monoolein bilayer) of the sponge phase and of the viscosity effect caused by propylene glycol and m-ALA.

Lipidic sponge phase crystallization of membrane proteins.

Bicontinuous lipidic cubic phases can be used as a host for growing crystals of membrane proteins. Since the cubic phase is stiff, handling is difficult and time-consuming. Moreover, the conventional cubic phase may interfere with the hydrophilic domains of membrane proteins due to the limited size of the aqueous pores. Here, we introduce a new crystallization method that makes use of a liquid analogue of the cubic phase, the sponge phase. This phase facilitates a considerable increase in the allowed size of aqueous domains of membrane proteins, and is easily generalised to a conventional vapour diffusion crystallisation experiment, including the use of nanoliter drop crystallization robots. The appearance of the sponge phase was confirmed by visual inspection, small-angle X-ray scattering and NMR spectroscopy. Crystals of the reaction centre from Rhodobacter sphaeroides were obtained by a conventional hanging-drop experiment, were harvested directly without the addition of lipase or cryoprotectant, and the structure was refined to 2.2 Angstroms resolution. In contrast to our earlier lipidic cubic phase reaction centre structure, the mobile ubiquinone could be built and refined. The practical advantages of the sponge phase make it a potent tool for crystallization of membrane proteins.

Aqueous self-assembly of phytantriol in ternary systems: effect of monoolein, distearoylphosphatidylglycerol and three water-miscible solvents.

The aqueous phase behavior of phytantriol (PT) in mixtures of monoolein (MO), distearoylphosphatidylglycerol (DSPG), propylene glycol (PG), polyethylene glycol 400 (PEG 400) and 2-methyl-2,4-pentanediol (MPD) was investigated by visual inspection, polarized light microscopy and small angle X-ray diffraction at room temperature. The phase diagrams of PT and MO in water are qualitatively very similar and PT/MO mixtures in excess water form one cubic phase of space group Pn3m irrespective of mixing ratio. The addition of the charged membrane lipid DSPG to the PT system gives rise to a considerable water swelling of the cubic phases as well as the occurrence of a cubic phase of space group Im3m. Whereas all three solvents studied give rise to a sponge (L3) phase in the MO-water system, this phase was only found when MPD was added to the PT-water system. The results are discussed with respect to the chemical differences between PT and MO.

The influence of PVP incorporation on moisture-induced surface crystallization of amorphous spray-dried lactose particles.

We have recently shown that atomic force microscopy (AFM) may be an appropriate method for characterisation of the re-crystallization of amorphous particles. In this study, spray-dried composite particles consisting of lactose and polyvinyl pyrrolidon (PVP) were characterised by AFM and electron spectroscopy for chemical analysis (ESCA), and their response on increasing the relative humidity (RH) was investigated. The PVP content in the particles used was 0, 5 or 25 wt.% of either PVP K17 or PVP K90. All composite particles were found to be enriched with PVP at the surface. The incorporation of PVP in the particles influenced the way the particles responded to an increase in RH. The specific RH interval in which the surface of the particles smoothened and the RH where crystallization could be detected, increased with an increase in the amount and molecular weight of the PVP in the particles. The crystallization kinetics of single particles was analysed with AFM and by utilising the JMAK equation. The rate constant for this transformation increased in an exponential manner with increasing RH. Furthermore, above the RH needed for the crystallization to occur, the exponential increase in the crystallization rate was larger for particles with higher polymer content which indicates that the stabilising effect decreases as the water content in the particles becomes higher. In this study we report a method for determination of crystallization kinetics on single composite particles, which is valuable when evaluating the effect of stabilisers in amorphous powders.

The importance of comorbidity in analysing patient costs in Swedish primary care.

BACKGROUND: The objective was to explore the usefulness of the morbidity risk adjustment system Adjusted Clinical Groups (ACG), in comparison with age and gender, in explaining and estimating patient costs on an individual level in Swedish primary health care. Data were retrieved from two primary health care centres in southeastern Sweden. METHODS: A cross-sectional observational study. Data from electronic patient registers from the two centres were retrieved for 2001 and 2002, and patients were grouped into ACGs, expressing the individual combination of diagnoses and thus the comorbidity. Costs per patient were calculated for both years in both centres. Cost data from one centre were used to create ACG weights. These weights were then applied to patients at the other centre. Correlations between individual patient costs, age, gender and ACG weights were studied. Multiple linear regression analyses were performed in order to explain and estimate patient costs. RESULTS: The variation in individual patient costs was substantial within age groups as well as within ACG weight groups. About 37.7% of the individual patient costs could be explained by ACG weights, and age and gender added about 0.8%. The individual patient costs in 2001 estimated 22.0% of patient costs in 2002, whereas ACG weights estimated 14.3%. CONCLUSION: ACGs was an important factor in explaining and estimating individual patient costs in primary health care. Costs were explained to only a minor extent by age and gender. However, the usefulness of the ACG system appears to be sensitive to the accuracy of classification and coding of diagnoses by physicians.

The effect of bacteriorhodopsin, detergent and hydration on the cubic-to-lamellar phase transition in the monoolein-distearoyl phosphatidyl glycerol-water system.

The cubic phase of monoolein (MO) has successfully been used for crystallization of membrane proteins. It is likely that the transition to a lamellar phase upon dehydration is important for the crystallization process, and that the internal dimensions of the lipid phases (i.e., water pore diameter) are crucial for the inclusion and the diffusion of membrane proteins. In the present study, we investigated the cubic-to-lamellar phase transitions in the MO-water and the MO-distearoyl phosphatidyl glycerol (DSPG) systems. The MO-water system was investigated by means of isothermal sorption and desorption microcalorimetry. We show that the transition from cubic to lamellar phase induced by desorption is driven by entropy. At 25 degrees C, this occurs at a water activity of 0.98 with a transition enthalpy of 860 J/mol (MO). The phase behavior was also investigated in the presence of a small amount of the transmembrane protein bacteriorhodopsin (bR), and a detergent, octyl glucoside (OG), and it was shown that both bR and OG stabilize the lamellar phase. Analogous results were obtained for the MO-DSPG-water system. The latter system resembles the MO-water system in that a cubic-to-lamellar phase transition is induced by dehydration, although the structural properties of these phases are slightly different. Finally, we demonstrate that bR can be crystallized from a cubic phase of MO-DSPG-buffer.

Diamond cubic phase of monoolein and water as an amphiphilic matrix for electrophoresis of oligonucleotides.

We used a cubic liquid crystal formed by the nonionic monoglyceride monoolein and water as a porous matrix for the electrophoresis of oligonucleotides. The diamond cubic phase is thermodynamically stable when in contact with a water-rich phase, which we exploit to run the electrophoresis in the useful submarine mode. Oligonucleotides are separated according to size and secondary structure by migration through the space-filling aqueous nanometer pores of the regular liquid crystal, but the comparatively slow migration means the cubic phase will not be a replacement for the conventional DNA gels. However, our demonstration that the cubic phase can be used in submarine electrophoresis opens up the possibility for a new matrix for electrophoresis of amphiphilic molecules. From this perspective, the results on the oligonucleotides show that water-soluble particles of nanometer size, typical for the hydrophilic parts of membrane-bound proteins, may be a useful separation motif. A charged contamination in the commercial sample of monoolein, most likely oleic acid that arises from its hydrolysis, restricts useful buffer conditions to a pH below 5.6.