XEN-45 in the management of early glaucoma surgery: A national Delphi consensus study.

BACKGROUND AND OBJECTIVE: Recommendations on general glaucoma management and the use of early minimally invasive and microincisional surgeries are limited. This study aimed to establish consensus regarding glaucoma management, focusing on the XEN-45 gel stent implant. METHODS: A Delphi consensus-driven process was used. The scientific committee led the study, identified the expert panel, and participated in elaborating the questionnaire. Fifty-one panelists were invited to complete, on a nine-point Likert scale, an 89-item questionnaire covering three topic blocks. Two Delphi rounds were performed. Consensus was achieved if ≥66.6% of panelists reached agreement or disagreement. RESULTS: Panelists agreed on 84 items related to the patients' quality of life, the therapeutic algorithm and patient profile, and surgical and pre- and post-operative management. Panelists agreed on the suitability of XEN stent implants to treat glaucoma at different stages and for different patient profiles: young patients, elderly or with significant comorbidities, and with myopic glaucoma, patients who failed previous surgeries, and with previous poor post-operative experience. XEN surgery was considered a therapeutic step prior to classic filtering surgery and a possible first surgical option in elderly patients with comorbidities and uncontrolled intraocular pressure. XEN surgery allows the patient to return to routine daily activities faster than conventional filtering surgeries and to reduce and/or eliminate topical treatments. CONCLUSIONS: This Delphi-driven consensus resulted in a series of general recommendations for glaucoma management, including those related to patient quality of life, therapeutic algorithm, and patient profile, and specific ones regarding the use of XEN stent gel surgery.

Expression profile of components of the ß-catenin destruction complex in oral dysplasia and oral cancer.

BACKGROUND: Oral cancer represents the sixth most common cancer in the world and is associated with 40-50% survival at 5 years. Within oral malignancies, oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, which, according to histopathological criteria, are referred to as oral dysplasia and their diagnosis are associated with higher rates of malignant transformation towards cancer. We recently reported that aberrant activation of the Wnt/ß­catenin pathway is due to overexpression of Wnt ligands in oral dysplasia. However, the expression of other regulators of this pathway, namely components of the ß-catenin destruction complex has not been explored in oral dysplasia. MATERIAL AND METHODS: Using immunohistochemical analyses, we evaluated nuclear expression of ß­catenin and its association with Wnt3a and Wnt5a. Likewise, components of the ß-catenin destruction complex, including Adenomatous Polyposis Coli (APC), Axin and Glycogen Synthase Kinase 3 beta (GSK-3ß) were also evaluated in oral dysplasia and OSCC biopsies. RESULTS: We found that moderate and severe dysplasia samples, which harbored increased expression of nuclear ß­catenin, depicted augmented cytoplasmic expression of GSK­3ß, Axin and APC, in comparison with OSCC samples. Also, GSK-3ß was found nuclear in mild dysplasia and OSCC samples, when compared with other study samples. CONCLUSIONS: Cytoplasmic levels of components of the ß-catenin destruction complex are increased in oral dysplasia and might be responsible of augmented nuclear ß­catenin.

A Commensal Strain of Staphylococcus epidermidis Overexpresses Membrane Proteins Associated with Pathogenesis When Grown in Biofilms.

Staphylococcus epidermidis has emerged as one of the major nosocomial pathogens associated with infections of implanted medical devices. The most important factor in the pathogenesis of these infections is the formation of bacterial biofilms. Bacteria grown in biofilms are more resistant to antibiotics and to the immune defence system than planktonic bacteria. In these infections, the antimicrobial therapy usually fails and the removal of the biofilm-coated implanted device is the only effective solution. In this study, three proteomic approaches were performed to investigate membrane proteins associated to biofilm formation: (i) sample fractionation by gel electrophoresis, followed by isotopic labelling and LC-MS/MS analysis, (ii) in-solution sample preparation, followed by isotopic labelling and LC-MS/MS analysis and (iii) in-solution sample preparation and label-free LC-MS/MS analysis. We found that the commensal strain S. epidermidis CECT 231 grown in biofilms expressed higher levels of five membrane and membrane-associated proteins involved in pathogenesis: accumulation-associated protein, staphylococcal secretory antigen, signal transduction protein TRAP, ribonuclease Y and phenol soluble modulin beta 1 when compared with bacteria grown under planktonic conditions. These results indicate that a commensal strain can acquire a pathogenic phenotype depending on the mode of growth.

Sociodemographic, reproductive and dietary predictors of organochlorine compounds levels in pregnant women in Spain.

Organochlorine pesticides and polychlorinated biphenyls (PCBs) are consistently found in human tissues. Serum levels of organochlorine compounds (OC) in pregnant women in particular have raised concern about possible harm to humans in the early phases of physical and behavioural development. The objective of the present study was to evaluate the association between concentration of OCs in serum of two cohorts of pregnant women from Gipuzkoa and Sabadell in Spain and socioeconomic, reproductive and dietary variables. Concentration of polychlorinated biphenyls (PCBs: 28, 52, 101, 118, 138, 153 and 180), hexachlorobenzene (HCB), beta and gamma-hexachlorocyclohexane (ß-HCH and γ-HCH), heptachlor epoxide, dichlorodiphenyl dichloroethylene (p,p'-DDE) and dichlorodiphenyl trichloroethane (p,p'-DDT) were measured in the serum of 1259 pregnant women. Associations between OCs and potential predictor variables were assessed using linear regression models adjusted for potential confounders. The compounds most commonly found in the serum were p,p'-DDE (99% of the samples) and PCB-153 (95% of the samples). Geometric means of serum concentrations (ng g⁻¹ lipid) of organochlorine pesticides were 110.0, 19.1, and 33.5 for p,p'-DDE, ß-HCH, and HCB respectively, while the geometric means of PCBs were 21.8, 38.9 and 26.9 for PCB 138, 153, and 180 respectively. The levels of all OCs increased with age. BMI was positively associated with the concentration of organochlorine pesticides but inversely related to PCB concentrations. The serum levels of OCs fell only after a cumulative period of breastfeeding of over a year. Levels of PCBs were related to fish intake, but in general dietary factors did not improve the explained variability of the concentrations of OCs. Overall, the levels of OCs found in the study are at the lower end of the range reported in Spain and other countries.

Focusing on glaucoma progression and the clinical importance of progression rate measurement: a review.

PURPOSE: This review aims to provide guidance in managing glaucoma patients more effectively. It focuses on the importance of detecting progression and measuring its rate within the management of primary open-angle glaucoma today. Recent findings strongly indicate that continued monitoring of visual fields (VFs) and reassessment of target intraocular pressures (IOPs) depending on VF progression rates are mandatory in the management of glaucoma. METHODS: Data on glaucoma progression from older as well as most recent literature findings are summarized in this article. In addition, the article elaborates on the scientific content from a series of lectures given by experts in the field during several international symposia on 'rate of progression' in 2008. RESULTS: This review summarizes key findings on the natural history of glaucoma and known factors for disease progression. It highlights the visual function changes observed as glaucoma progresses and discusses disease impact on patients' quality of life. Findings support the need to obtain information on rate of progression and its importance for clinical management. Practical ways to measure rate of progression are given by new software options to help measure major parameters. Finally, on the basis of a patient's individual rate of progression therapeutic options are assessed, such as maximum medical therapy with fixed combinations. CONCLUSIONS: Estimating a patient's individual rate of VF progression by using newly developed analyses will be helpful to forecast the potential future development of the glaucoma. An individualized treatment approach then requires that in patients in whom the risk of becoming visually impaired or blind during their lifetime is higher, a more intensive medical IOP-lowering therapy such as fixed combinations can be considered as treatment option.

Serum levels of polychlorinated dibenzodioxins and dibenzofurans and PCBs in the general population living near an urban waste treatment plant in Biscay, Basque Country.

Levels of PCDD/Fs and dioxin-like PCBs were measured in 16 pooled samples of serum from a total of 322 adults in the general population, to coincide with the start-up of a new municipal solid urban waste treatment plant in Biscay, Basque Country (Spain). Two hundred and eighty-three individual serum samples were also obtained, in which the most common PCBs (28, 52, 101, 118, 138, 153 and 180) were quantified. The samples were taken from four geographical zones: two from the metropolitan area of Bilbao, located less than 2 km from the plant and with high traffic density (Zones E1 and E2), a third located 5 km from the plant in an urban area of Bilbao, also with high traffic density (Zone C1) and the fourth located 20 km from the plant, in a municipality with minimal industrial activity and low traffic density (Zone C2), the latter two being out of the path of the prevailing winds. The median levels of dioxins+furans were similar by zone: E1=24.3, E2=27.3, C1=21.3, C2=18.8 pg g(-1) lipid (p=0.362); by sex: 20.2 vs. 22.6 pg g(-1) lipid in men and women (p=0.328); and by age: 20.8 vs. 21.3 pg g(-1) lipid in subjects aged 20-44 and 45-69 (p=0.505). No detectable levels of PCBs 52 and 101 were found. Significant differences by zone were found only for PCB 180 (p=0.041), with higher values in Zone C2, the zone with the lowest presumed contamination levels. Dioxin-like PCBs (p<0.001) and the most common PCBs (138, 153, 180) (p<0.001) were both statistically associated with age, higher values being found in the 45-69 age group.

High titers of mucosal and systemic anti-PrP antibodies abrogate oral prion infection in mucosal-vaccinated mice.

Significant outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. These disorders are associated with a conformational change of a normal protein, PrP(C) (C for cellular), to a toxic and infectious form, PrP(Sc) (Sc for scrapie). None of the prionoses currently have an effective treatment. Some forms of prion disease are thought to be spread by oral ingestion of PrP(Sc), such as chronic wasting disease and variant Creutzfeldt-Jakob disease. Attempts to obtain an active immunization in wild-type animals have been hampered by auto-tolerance to PrP and potential toxicity. Previously, we demonstrated that it is possible to overcome tolerance and obtain a specific anti-PrP antibody response by oral inoculation of the PrP protein expressed in an attenuated Salmonella vector. This past study showed that 30% of vaccinated animals were free of disease more than 350 days post-challenge. In the current study we have both optimized the vaccination protocol and divided the vaccinated mice into low and high immune responder groups prior to oral challenge with PrP(Sc) scrapie strain 139A. These methodological refinements led to a significantly improved therapeutic response. 100% of mice with a high mucosal anti-PrP titer immunoglobulin (Ig) A and a high systemic IgG titer, prior to challenge, remained without symptoms of PrP infection at 400 days (log-rank test P<0.0001 versus sham controls). The brains from these surviving clinically asymptomatic mice were free of PrP(Sc) infection by Western blot and histological examination. These promising findings suggest that effective mucosal vaccination is a feasible and useful method for overcoming tolerance to PrP and preventing prion infection via an oral route.

Practical recommendations for measuring rates of visual field change in glaucoma.

To date, there has been a lack of evidence-based guidance on the frequency of visual field examinations required to identify clinically meaningful rates of change in glaucoma. The objective of this perspective is to provide practical recommendations for this purpose. The primary emphasis is on the period of time and number of examinations required to measure various rates of change in mean deviation (MD) with adequate statistical power. Empirical data were used to obtain variability estimates of MD while statistical modelling techniques derived the required time periods to detect change with various degrees of visual field variability. We provide the frequency of examinations per year required to detect different amounts of change in 2, 3 and 5 years. For instance, three examinations per year are required to identify an overall change in MD of 4 dB over 2 years in a patient with average visual field variability. Recommendations on other issues such as examination type, strategy and quality are also made.

Prevalence and management of gastrointestinal complications in lung transplant patients: MITOS study group.

INTRODUCTION: No studies have yet been performed to evaluate the prevalence of gastrointestinal (GI) complications in solid organ transplant recipients in Spain. MATERIALS AND METHODS: An observational, cross-sectional study to evaluate the prevalence and management of GI complications in transplanted patients was conducted via a written questionnaire given to doctors at their practice. RESULTS: A total of 58 lung transplant recipients were included. Their mean age was 52.6 +/- 10.8 years; 65% of the patients were men; and the mean time since the transplant was 2.1 +/- 2.3 years. GI complications were seen in 48.6% of the lung transplant patients. Regarding the management, the most frequently used measure was the prescription of gastric protectors (70.5%). In seven patients, the immunosuppressive treatment was also modified (reduced, discontinued temporarily, or discontinued permanently); however, the figure is so low that no conclusions can be drawn from this result. CONCLUSIONS: The prevalence of GI complications in lung transplant was over 50%, and these complications affected patients' daily activities in most cases. In lung transplant recipients, there was a higher prevalence of nausea and abdominal pain and a lower of diarrhea and dyspepsia than what was observed in other type of transplant recipients.

Is vaccination against transmissible spongiform encephalopathy feasible?

Prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformation change of the cellular form of a normal, self-protein called a prion protein (PrP(c) [C for cellular]) to a pathological and infectious conformation known as scrapie form (PrPsc [Sc for scrapie]). Currently, all prion diseases are without effective treatment and are universally fatal. The emergence of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease has highlighted the need to develop possible therapies. In Alzheimer's disease (AD), which has similarities to prion diseases, both passive and active immunisation have been shown to be highly effective at preventing disease and cognitive deficits in model animals. In a human trial of active vaccination in AD, despite indications of cognitive benefits in patients with an adequate humoral response, 6% of patients developed significant complications related to excessive cell-mediated immunity. This experience highlights that immunotherapies designed to be directed against a self-antigen have to finely balance an effective humoral immune response with potential autoimmune toxicity. Many prion diseases have the gut as a portal of infectious agent entry. This makes mucosal immunisation a potentially very attractive method to partially or completely prevent prion entry across the gut barrier and to also produce a modulated immune response that is unlikely to be associated with any toxicity. The authors' recent results using an attenuated Salmonella vaccine strain expressing the prion protein show that mucosal vaccination can partially protect against prion infection from a peripheral source, suggesting the feasibility of this approach.

12-week study comparing the fixed combination of brimonidine and timolol with concomitant use of the individual components in patients with glaucoma and ocular hypertension.

PURPOSE: To evaluate the efficacy and safety of fixed-combination brimonidine tartrate 0.2%/timolol 0.5% ophthalmic solution dosed BID and demonstrate non-inferiority to concomitant use of brimonidine tartrate 0.2% BID and timolol 0.5% BID in glaucoma and ocular hypertension patients with intraocular pressure (IOP) uncontrolled on monotherapy. METHODS: Randomized, multicenter, double-masked, parallel-group study involving 371 patients with inadequate IOP control (IOP from 22 to 34 mmHg) after > or =3 weeks of run-in on any monotherapy. Patients were treated with fixed-combination brimonidine/timolol BID (fixed-combination group, n = 188) or concomitant brimonidine BID and timolol BID (concomitant group, n = 183). IOP was assessed pre-dose and 2 hours after morning dosing at weeks 2, 6, and 12. RESULTS: A total of 355 patients (96%) completed the study. Patient demographics, run-in monotherapy, and baseline mean IOP on monotherapy were comparable between treatment groups. During follow-up, the mean reduction from baseline IOP was significant (p < 0.001) at all time points and ranged from 4.4 to 5.3 mmHg in each group. Brimonidine/timolol fixed combination was as effective as concomitant therapy with respect to mean IOP and mean change from baseline IOP at all time points and visits. Between-group differences were < or =0.35 mmHg for mean IOP and < or 0.30 mmHg for mean change from baseline IOP; none were significant. No unexpected side effects were associated with the fixed combination. Both treatments were well tolerated with no difference in adverse events between groups. CONCLUSIONS: Brimonidine/timolol fixed-combination therapy is as safe and effective as concomitant treatment with the individual components. Its simplified dosing regimen has the potential to improve compliance.

Mucosal vaccination delays or prevents prion infection via an oral route.

In recent years major outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. These disorders are associated with a conformational change of a normal protein, PrP(C) (prion protein cellular), to a toxic and infectious form, PrP(Sc) (prion protein scrapie). None of the prionoses currently have an effective treatment. A limited number of active immunization approaches have been shown to slightly prolong the incubation period of prion infection. Active immunization in wild-type animals is hampered by auto-tolerance to PrP and potential toxicity. Here we report that mucosal vaccination with an attenuated Salmonella vaccine strain expressing the mouse PrP, is effective at overcoming tolerance to PrP and leads to a significant delay or prevention of prion disease in mice later exposed orally to the 139A scrapie strain. This mucosal vaccine induced gut anti-PrP immunoglobulin (Ig)A and systemic anti-PrP IgG. No toxicity was evident with this vaccination approach. This promising finding suggests that mucosal vaccination may be a useful method for overcoming tolerance to PrP and preventing prion infection among animal and potentially human populations at risk.

12-week study comparing the fixed combination of brimonidine and timolol with concomitant use of the individual components in patients with glaucoma and ocular hypertension.

PURPOSE: To evaluate the efficacy and safety of fixed-combination brimonidine tartrate 0.2%/timolol 0.5% ophthalmic solution dosed BID and demonstrate non-inferiority to concomitant use of brimonidine tartrate 0.2% BID and timolol 0.5% BID in glaucoma and ocular hypertension patients with intraocular pressure (IOP) uncontrolled on monotherapy. METHODS: Randomized, multicenter, double-masked, parallel-group study involving 371 patients with inadequate IOP control (IOP from 22 to 34 mmHg) after >=3 weeks of run-in on any monotherapy. Patients were treated with fixed-combination brimonidine/timolol BID (fixed-combination group, n=188) or concomitant brimonidine BID and timolol BID (concomitant group, n=183). IOP was assessed pre-dose and 2 hours after morning dosing at weeks 2, 6, and 12. RESULTS: A total of 355 patients (96%) completed the study. Patient demographics, run-in monotherapy, and baseline mean IOP on monotherapy were comparable between treatment groups. During follow-up, the mean reduction from baseline IOP was significant (p<0.001) at all time points and ranged from 4.4 to 5.3 mmHg in each group. Brimonidine/timolol fixed combination was as effective as concomitant therapy with respect to mean IOP and mean change from baseline IOP at all time points and visits. Between-group differences were <=0.35 mmHg for mean IOP and <=0.30 mmHg for mean change from baseline IOP; none were significant. No unexpected side effects were associated with the fixed combination. Both treatments were well tolerated with no difference in adverse events between groups. CONCLUSIONS: Brimonidine/timolol fixed-combination therapy is as safe and effective as concomitant treatment with the individual components. Its simplified dosing regimen has the potential to improve compliance. (Eur J Ophthalmol 2005; 15: 581-90).

Cholesterol modulation of sphingomyelinase activity at physiological temperatures.

Bacillus cereus sphingomyelinase activity was assayed on large unilamellar vesicles composed of sphingomyelin (SM)/cholesterol (Ch) mixtures at varying proportions. Natural (egg) SM was used with a gel-fluid transition temperature at ca. 40 degrees C. When the enzyme was assayed at 37 degrees C, the activity on pure SM was exceedingly low, but a small increase was observed as soon as some Ch was added, and a large enhancement of activity occurred with Ch proportions above 25 mol%. The data were interpreted in terms of sphingomyelinase activity being higher in the cholesterol-induced liquid-ordered phase than in the gel phase. The abrupt increase in activity above 25 mol% Ch would occur as a result of a change in domain connectivity, when the Ch-rich liquid-ordered domains coalesced. In equimolar SM/Ch mixtures, that were in the liquid-ordered state in a wide range of temperatures, sphingomyelinase activity was virtually constant in the 30-70 degrees C range. The results demonstrate that at the mammalian and bird physiological temperatures Ch modulates sphingomyelinase activity, and that this can occur precisely because most SM have a gel-fluid transition temperature above the physiological temperature range. In addition, Ch activation of sphingomyelinase and the strong affinity of Ch for SM allow the rapid, localised and self-contained production of the metabolic signal ceramide in specific microdomains (rafts).

Purification and characterization of insulin-mimetic inositol phosphoglycan-like molecules from grass pea (Lathyrus sativus) seeds.

BACKGROUND: Signal transduction through the hydrolysis of glycosyl-phosphatidylinositol (GPI) leading to the release of the water-soluble inositol phosphoglycan (IPG) molecules has been demonstrated to be important for mediating some of the actions of insulin and insulin-like growth factor-I (IGF-I). MATERIALS AND METHODS: In the present study, GPI from grass pea (Lathyrus sativus) seeds has been purified and partially characterized on the basis of its chromatographic properties and its compositional analysis. RESULTS: The results indicate that it shows similarities to GPI previously isolated from other sources such as rat liver. IPG was generated from L. sativus seed GPI by hydrolysis with a GPI-specific phospholipase D (GPI-PLD). This IPG inhibited protein kinase A (PKA) in an in vitro assay, caused cell proliferation in explanted cochleovestibular ganglia (CVG), and decreased 8-Br-cAMP-induced phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in cultured hepatoma cells. CONCLUSIONS: Our data indicate that L. sativus seed IPG possess insulin-mimetic activities. This may explain why L. sativus seeds have been used in some traditional medicines to ameliorate diabetic symptoms.

Interaction of cholesterol with sphingomyelin in mixed membranes containing phosphatidylcholine, studied by spin-label ESR and IR spectroscopies. A possible stabilization of gel-phase sphingolipid domains by cholesterol.

The ESR spectra from different positional isomers of sphingomyelin and phosphatidylcholine spin-labeled in their acyl chain have been studied in sphingomyelin(cerebroside)-phosphatidylcholine mixed membranes that contain cholesterol. The aim was to investigate mechanisms by which cholesterol could stabilize possible domain formation in sphingolipid-glycerolipid membranes. The outer hyperfine splittings in the ESR spectra of sphingomyelin and phosphatidylcholine spin-labeled on the 5 C atom of the acyl chain were consistent with mixing of the components, but the perturbations on adding cholesterol were greater in the membranes containing sphingomyelin than in those containing phosphatidylcholine. Infrared spectra of the amide I band of egg sphingomyelin were shifted and broadened in the presence of cholesterol to a greater extent than the carbonyl band of phosphatidylcholine, which was affected very little by cholesterol. Two-component ESR spectra were observed from lipids spin-labeled on the 14 C atom of the acyl chain in cholesterol-containing membranes composed of sphingolipids, with or without glycerolipids (sphingomyelin/cerebroside and sphingomyelin/cerebroside/phosphatidylcholine mixtures). These results indicate the existence of gel-phase domains in otherwise liquid-ordered membranes that contain cholesterol. In the gel phase of egg sphingomyelin, the outer hyperfine splittings of sphingomyelin spin-labeled on the 14-C atom of the acyl chain are smaller than those for the corresponding spin-labeled phosphatidylcholine. In the presence of cholesterol, this situation is reversed; the outer splitting of 14-C spin-labeled sphingomyelin is then greater than that of 14-C spin-labeled phosphatidylcholine. This result provides some support for the suggestion that transbilayer interdigitation induced by cholesterol stabilizes the coexistence of gel-phase and "liquid-ordered" domains in membranes containing sphingolipids.

Early stages of LDL oxidation: apolipoprotein B structural changes monitored by infrared spectroscopy.

Changes in the conformation of apoliprotein B-100 in the early stages of copper-mediated low density lipoprotein oxidation have been monitored by infrared spectroscopy. During the lag phase no variation in structure is observed, indicating that copper binding to the protein does not significantly affect its structure. In the propagation phase, while hydroperoxides are formed but the protein is not modified, no changes in secondary structure are observed, but the thermal profile of the band corresponding to alpha-helix is displaced in frequency, indicating changes in tertiary structure associated with this conformation but not with beta-sheet components. When aldehyde formation starts, a decrease of approximately 3% in the area of bands corresponding to alpha-helix and beta-sheet is produced, concomitantly with an increase in beta-turns and unordered structure. The two bands corresponding to beta-turns vary as well under these conditions, indicating changes in these structures. Also at this stage the thermal profile shows variations in frequency for the bands corresponding to both alpha-helix and beta-sheet. The results are consistent with the hypothesis that as soon as the polyunsaturated fatty acids from the particle core are modified, this change is reflected at the surface, in the alpha-helical components contacting the monolayer.

Diacylglycerol effects on phosphatidylinositol-specific phospholipase C activity and vesicle fusion.

Diacylglycerol increased the hydrolytic activity of phosphatidylinositol-specific phospholipase C on large unilamellar vesicles containing 5-40% phosphatidylinositol. Moreover, diacylglycerol increased the rate and extent of vesicle fusion (contents mixing) induced by the enzyme. Kinetic studies of intervesicular lipid mixing revealed that fusion was limited by the frequency of contacts involving two diacylglycerol-rich domains.