Image processing tools for the validation of CryoEM maps.

The number of maps deposited in public databases (Electron Microscopy Data Bank, EMDB) determined by cryo-electron microscopy has quickly grown in recent years. With this rapid growth, it is critical to guarantee their quality. So far, map validation has primarily focused on the agreement between maps and models. From the image processing perspective, the validation has been mostly restricted to using two half-maps and the measurement of their internal consistency. In this article, we suggest that map validation can be taken much further from the point of view of image processing if 2D classes, particles, angles, coordinates, defoci, and micrographs are also provided. We present a progressive validation scheme that qualifies a result validation status from 0 to 5 and offers three optional qualifiers (A, W, and O) that can be added. The simplest validation state is 0, while the most complete would be 5AWO. This scheme has been implemented in a website https://biocomp.cnb.csic.es/EMValidationService/ to which reconstructed maps and their ESI can be uploaded.

Expression of odorant-binding proteins in mouthpart palps of the desert locust Schistocerca gregaria.

Odorant-binding proteins (OBPs) are essential molecular elements of the insect chemosensory system, which is composed of the antennae and the mouthpart palps (maxillary and labial). In this study, we have analysed the expression and the sensilla specificity of 14 OBP subtypes in the palps of the desert locust Schistocerca gregaria. The locust palps comprise only a low number of sensilla basiconica but a high number of sensilla chaetica. Employing a variety of approaches, we found that only a subset of the antennal OBP repertoire was expressed in both palp types. These OBPs were previously shown to be expressed either in sensilla basiconica or sensilla chaetica of the antennae. Comparing the expression pattern in the two chemosensory organs revealed similarities and differences; most remarkably, two OBP subtypes, OBP6 and OBP8, were found in both sensilla types on palps, whereas on the antennae they were solely expressed in one sensillum type. Together, the data indicate a differential, but partly overlapping, expression of OBPs in the two sensilla types of the palps. The differences in the expression pattern of OBP subtypes between antennae and palps might be indicative for distinct functions of the OBPs in the two chemosensory organs.

[Quality of life and depression in hearing-impairment : A German survey]. / Lebensqualität und Depression bei Hörminderung : Eine deutsche Bedarfsanalyse.

BACKGROUND: Hearing-impairment can lead to a reduced quality of life and thus represents a vulnerability factor for mental disorders. OBJECTIVE: This study represents the first psychiatric analysis of subjective quality of life and depression in people with hearing-impairment in Germany. MATERIALS AND METHODS: The patient group included 30 hearing-impaired participants (27 women, 3 men) with a current or previous mental disorder and/or psychiatric/psychotherapeutic treatment (age: mean, M = 49.67 years; standard deviation, SD = 13.54 years). The control group consisted of 22 hearing-impaired participants (16 women, 6 men) without mental disorders or treatment (age: M = 52.41 years, SD = 17.30 years). Besides sociodemographic variables, we registered onset/extent of the various hearing-impairments and hearing aid provision. Both groups underwent extensive diagnostic assessment comprising subjective functional impairment (Sheehan Disability Scale, SDS), health-related quality of life (SF-36 Health Survey), and depressive symptoms (Beck Depression Inventory, BDI-II). RESULTS: Groups did not differ significantly in terms of sociodemographic variables such as age, gender, or intelligence. Participants of the patient group had a significantly greater subjective impairment, a lower quality of life, and more pronounced symptoms of depression. The invasiveness of the hearing aid (i. e., cochlear implant) as well as the timepoint of hearing-impairment onset (postlingually) appear to serve as vulnerability factors for mental health problems in this group. CONCLUSION: Our results indicate that besides delivering high-quality acoustic care, practitioners should continuously check patients' requirements for psychosocial treatment due to a loss of quality of life. The development of a specific psychotherapeutic treatment for hearing-impaired clients requires additional research focused on protective and vulnerability factors which may influence the emergence of mental disorders in these patients.

Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates.

We present a soft x-ray angle-resolved photoemission spectroscopy study of overdoped high-temperature superconductors. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No k_{z} dispersion is observed along the nodal direction, whereas a significant antinodal k_{z} dispersion is identified for La-based cuprates. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La_{2-x}Sr_{x}CuO_{4} cannot be assigned to the van Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat.

Three-Dimensional Electronic Structure of the Type-II Weyl Semimetal WTe_{2}.

By combining bulk sensitive soft-x-ray angular-resolved photoemission spectroscopy and first-principles calculations we explored the bulk electron states of WTe_{2}, a candidate type-II Weyl semimetal featuring a large nonsaturating magnetoresistance. Despite the layered geometry suggesting a two-dimensional electronic structure, we directly observe a three-dimensional electronic dispersion. We report a band dispersion in the reciprocal direction perpendicular to the layers, implying that electrons can also travel coherently when crossing from one layer to the other. The measured Fermi surface is characterized by two well-separated electron and hole pockets at either side of the Γ point, differently from previous more surface sensitive angle-resolved photoemission spectroscopy experiments that additionally found a pronounced quasiparticle weight at the zone center. Moreover, we observe a significant sensitivity of the bulk electronic structure of WTe_{2} around the Fermi level to electronic correlations and renormalizations due to self-energy effects, previously neglected in first-principles descriptions.

-318C/T polymorphism of the CTLA-4 gene is an independent risk factor for RBC alloimmunization among sickle cell disease patients.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule is expressed on T-lymphocyte membrane and negatively influences the antigen-presenting process. Reduced expression of CTLA-4 due to gene polymorphisms is associated with increased risk of autoimmune disorders, whose physiopathology is similar to that of post-transfusion red blood cell (RBC) alloimmunization. Our goal was to evaluate if polymorphisms of CTLA-4 gene that affect protein expression are associated with RBC alloimmunization. This was a case-control study in which 134 sickle cell disease (SCD) patients and 253 non-SCD patients were included. All patients were genotyped for the polymorphisms 49A/G and -318C/T of CTLA-4 gene. The genotype frequency of -318C/T differed significantly between alloimmunized and nonalloimmunized SCD patients, irrespective of clinical confounders (p = .016). SCD patients heterozygous for -318T allele presented higher risk of alloantibody development (OR: 5.4, CI: 1.15-25.6). In conclusion, the polymorphism -318C/T of CTLA-4 gene is associated with RBC alloimmunization among SCD patients. This highlights the role played by CTLA-4 on post-transfusion alloantibody development.

[Analysis of the German state medical examination regarding psychiatrically relevant topics]. / Staatsexamensanalyse hinsichtlich psychiatrisch relevanter Themen.

BACKGROUND: The second part of the state medical examination is an essential part of medical education in Germany. From 2006 until 2013, the second and third parts of the licensing examination were combined, thus earning this examination the reputation of being notoriously difficult to pass. The aim of this exploratory study was to examine psychiatric and psychotherapeutic questions in the written part of the second examination. OBJECTIVES: This study analyzed the proportion of psychiatric and psychotherapeutic questions in the written part of the second leg of the German state medical examination. In a second step, a more detailed analysis aimed to identify more specific subject areas and to allocate diagnoses according to ICD-10, allowing a detailed overview of the presence of psychiatric topics. MATERIAL AND METHODS: A total of 8 examinations from fall 2010 up to spring 2014 a were included in the analysis. Every examination comprised 320 questions, thus a total of 2560 questions were analyzed. All questions pertaining to psychiatric or psychotherapeutic topics were included. Questions were categorized according to a predefined set of subject areas and an ICD-10 diagnosis. RESULTS: Out of the total of 2560 questions analyzed, 166 were categorized as being in psychiatry or psychotherapy, with each examination comprising an average of 20.75 (SD = 5.80) relevant questions. Most questions were allocated to the subject area of pharmacology (n = 53), followed by psychopathologic assessment (n = 27) and psychotherapy (n = 12). Sorted according to ICD-10 criteria, most questions could be assigned to the F3 category, the affective disorders group (21.9 %, n = 35). CONCLUSION: In comparison to the actual strain placed on the healthcare system, the results indicate an underrepresentation of psychiatric disorders in the second part of the German state medical examination. The distribution of specific disorders mirrors the actual distribution at least in part; however, certain practically relevant disorders are severely underrepresented.

Larval sensilla of the moth Heliothis virescens respond to sex pheromone components.

Female-released sex pheromones orchestrate the mating behaviour of moths. Recent studies have shown that sex pheromones not only attract adult males but also caterpillars. Single sensillum recordings revealed that larval antennal sensilla of the moth Heliothis virescens respond to specific sex pheromone components. In search for the molecular basis of pheromone detection in larvae, we found that olfactory sensilla on the larval antennae are equipped with the same molecular elements that mediate sex pheromone detection in adult male moths, including the Heliothis virescens receptors 6 (HR6) and HR13, as well as sensory neurone membrane protein 1 (SNMP1). Thirty-eight olfactory sensory neurones were identified in three large sensilla basiconica; six of these are considered as candidate pheromone responsive cells based on the expression of SNMP1. The pheromone receptor HR6 was found to be expressed in two cells and the receptor HR13 in three cells. These putative pheromone responsive neurones were accompanied by cells expressing pheromone-binding protein 1 (PBP1) and PBP2. The results indicate that the responsiveness of larval sensilla to female-emitted sex pheromones is based on the same molecular machinery as in the antennae of adult males.

Editor's Choice - Fluid-Structure Interaction Simulations of Aortic Dissection with Bench Validation.

INTRODUCTION: The blood flow and stresses in the flap in aortic dissections are not well understood. Validated fluid-structure interaction (FSI) simulations of the interactions between the blood flow and the flap will provide insight into the dynamics of aortic dissections and may lead to developments of novel therapeutic approaches. METHODS: A coupled, two-way blood flow and flap wall computational model was developed. The Arbitrary Lagrange-Eulerian method was used, which allowed the fluid mesh to deform. Inflow velocity waveforms from a pulse duplicator system were used in the simulations. RESULTS: The velocities for true lumen (TL) and false lumen (FL) were not significantly different between bench and simulation. The dynamics of the TL % cross-sectional area (CSA) during the cycle was similar between the bench and computational simulations, with the TL %CSA being most reduced near peak systole of the cycle. The experimental distal measurements had significantly lower velocities, likely due to the spatially heterogeneous flow distally. The conservation of mass and validity of simulations were confirmed. Additionally, regions of stress concentrations were found on the flap leading edge, towards the corners, and through the entire vessel wall. The pressure gradient across the FL results in a net force on the flap. CONCLUSION: The FSI flow velocities in the TL and the FL as well as the dynamics of the CSA during the cardiac cycle were validated by bench experiments. The validated FSI model may provide insights into aortic dissection including the stresses on the dissection flap and related flow disturbance, which may be subdued by novel therapeutic approaches. Simulations of more realistic human aortic dissections and the effects of current therapeutic approaches such as stent-graft can be developed in the future using the validated computational platform provided in the present study.

Effects of Varied Versus Constant Loading Zones on Muscular Adaptations in Trained Men.

The purpose of this study was to compare the effects of a protocol employing a combination of loading zones vs. one employing a constant medium-repetition loading zone on muscular adaptations in resistance-trained men. 19 trained men (height=176.9±7.0 cm; body mass=83.1±11.8 kg; age=23.3±2.9 years) were randomly assigned to 1 of 2 experimental groups: a constant-rep resistance training (RT) routine (CONSTANT) that trained using 8-12 RM per set, or a varied-rep RT routine (VARIED) that trained with 2-4 RM per set on Day 1, 8-12 RM per set on Day 2, and 20-30 RM on Day 3 for 8 weeks. Results showed that both groups significantly increased markers of muscle strength, muscle thickness, and local muscular endurance, with no differences noted between groups. Effect sizes favored VARIED over CONSTANT condition for elbow flexor thickness (0.72 vs. 0.57), elbow extensor thickness (0.77 vs. 0.48), maximal bench press strength (0.80 vs. 0.57), and upper body muscle endurance (1.91 vs. 1.28). In conclusion, findings indicate that both varied and constant loading approaches can promote significant improvements in muscular adaptations in trained young men.

The sensory neurone membrane protein SNMP1 contributes to the sensitivity of a pheromone detection system.

Male moths detect female-released sex pheromones with extraordinary sensitivity. The remarkable sensory ability is based on a cooperative interplay of pheromone binding proteins in the lymph of hair-like sensilla trichodea and pheromone receptors in the dendrites of sensory neurones. Here we examined whether in Heliothis virescens the so-called 'sensory neurone membrane protein 1' (SNMP1) may contribute to responsiveness to the pheromone component, (Z)-11-hexadecenal (Z11-16:Ald). By means of immunohistochemistry and in situ hybridization we demonstrated that SNMP1 is in fact present in cells expressing the Z11-16:Ald receptor HR13 and the dendrites of sensory neurones. To assess a possible function of SNMP1 we monitored the responsiveness of cell lines that expressed HR13 alone or the combination SNMP1/HR13 to stimulation with Z11-16:Ald by calcium imaging. It was found that SNMP1/HR13 cells were 1000-fold more sensitive to pheromone stimulation compared with HR13 cells. In contrast, cells that expressed HR13 and the non-neuronal SNMP2-type showed no change in pheromone sensitivity. Overall, our reconstitution experiments demonstrate that the presence of SNMP1 significantly increases the HR13-based responsiveness of cells to Z11-16:Ald, suggesting that SNMP1 also contributes to the response of the antennal neurones and thus to the remarkable sensitivity of the pheromone detection system.

Characterization of a bioprosthetic bicuspid venous valve hemodynamics: implications for mechanism of valve dynamics.

BACKGROUND: Chronic venous insufficiency (CVI) of the lower extremities is a common clinical problem. Although bioprosthetic valves have been proposed to treat severe reflux, clinical success has been limited due to thrombosis and neointima overgrowth of the leaflets that is, in part, related to the hemodynamics of the valve. A bioprosthetic valve that mimics native valve hemodynamics is essential. METHODS: A computational model of the prosthetic valve based on realistic geometry and mechanical properties was developed to simulate the interaction of valve structure (fluid-structure interaction, FSI) with the surrounding flow. The simulation results were validated by experiments of a bioprosthetic bicuspid venous valve using particle image velocimetry (PIV) with high spatial and temporal resolution in a pulse duplicator (PD). RESULTS: Flow velocity fields surrounding the valve leaflets were calculated from PIV measurements and comparisons to the FSI simulation results were made. Both the spatial and temporal results of the simulations and experiments were in agreement. The FSI prediction of the transition point from equilibrium phase to valve-closing phase had a 7% delay compared to the PD measurements, while the PIV measurements matched the PD exactly. FSI predictions of reversed flow were within 10% compared to PD measurements. Stagnation or stasis regions were observed in both simulations and experiments. The pressure differential across the valve and associated forces on the leaflets from simulations showed the valve mechanism to be pressure driven. CONCLUSIONS: The flow velocity simulations were highly consistent with the experimental results. The FSI simulation and force analysis showed that the valve closure mechanism is pressure driven under the test conditions. FSI simulation and PIV measurements demonstrated that the flow behind the leaflet was mostly stagnant and a potential source for thrombosis. The validated FSI simulations should enable future valve design optimizations that are needed for improved clinical outcome.

Role of sinus in prosthetic venous valve.

BACKGROUND: The majority of bioprosthetic venous valves do not have a sinus pocket and, in practice, they are often placed in non-sinus segments of the veins. The aim of this study is to investigate the effect of the sinus pocket on the flow dynamics in a prosthetic valve. METHODS: A bench top in vitro experiment was set up at physiological flow conditions to simulate the flow inside a venous system. Bicuspid bioprosthetic valves with different leaflet lengths (5 and 10 mm) were tested in tubes with and without a sinus pocket and the flows around the valve were visualized by particle image velocimetry (PIV). Velocity data measurements were made and the vorticity was calculated in the with- and without-sinus set-ups. RESULTS: PIV measurements showed that vortex structure was maintained by the sinus. For the 10-mm leaflet length design with sinus, the jet width at the exit of the valve was 59% of that without sinus. For the 5-mm design with sinus, the jet width was 73% of the valve without sinus. Flow from the sinus region was entrained into the main jet observed near the exit of the sinus and altered the flow at the near wall region. CONCLUSIONS: The sinus pocket alters the flow around the valve and functions as flow regulator to smooth the flow pattern around the valve. The vortical structure inside the sinus is maintained at the valve leaflet tip during the valve cycle. For the prosthetic valve designated to be placed without a sinus, a shorter leaflet length is preferable and performs more closely to the valve with sinus.

[Computed tomography in multiple trauma patients: technical aspects, work flow, and dose reduction]. / Polytrauma-Computertomographie : Technische Grundlagen, Workflow und Dosisreduktion.

CLINICAL/METHODICAL ISSUE: Patients with severe, life-threatening trauma require a fast and accurate clinical and imaging diagnostic workup during the first phase of trauma management. STANDARD RADIOLOGICAL METHODS: Early whole-body computed tomography has clearly been proven to be the current standard of care of these patients. METHODICAL INNOVATIONS: A similar imaging quality can be achieved in the multiple trauma setting compared with routine imaging especially using rapid, latest generation computed tomography (CT) scanners. PERFORMANCE: This article encompasses a detailed view on the use of CT in patients with life-threatening trauma. A special focus is placed on radiological procedures in trauma units and on the methods for CT workup in routine cases and in challenging situations. Another focus discusses the potential of dose reduction of CT scans in multiple trauma as well as the examination of children with severe trauma. ACHIEVEMENTS: Various studies have demonstrated that early whole-body CT positively correlates with low morbidity and mortality and is clearly superior to the use of other imaging modalities. PRACTICAL RECOMMENDATIONS: Optimal trauma unit management means a close cooperation between trauma surgeons, anesthesiologists and radiologists, whereby the radiologist is responsible for a rapid and accurate radiological workup and the rapid communication of imaging findings. However, even in the trauma setting, aspects of patient radiation doses should be kept in mind.

Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity.

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.

Extension of the KLI approximation toward the exact optimized effective potential.

The integral equation for the optimized effective potential (OEP) is utilized in a compact form from which an accurate OEP solution for the spin-unrestricted exchange-correlation potential, Vxcσ, is obtained for any assumed orbital-dependent exchange-correlation energy functional. The method extends beyond the Krieger-Li-Iafrate (KLI) approximation toward the exact OEP result. The compact nature of the OEP equation arises by replacing the integrals involving the Green's function terms in the traditional OEP equation by an equivalent first-order perturbation theory wavefunction often referred to as the "orbital shift" function. Significant progress is then obtained by solving the equation for the first order perturbation theory wavefunction by use of Dalgarno functions which are determined from well known methods of partial differential equations. The use of Dalgarno functions circumvents the need to explicitly address the Green's functions and the associated problems with "sum over states" numerics; as well, the Dalgarno functions provide ease in dealing with inherent singularities arising from the origin and the zeros of the occupied orbital wavefunctions. The Dalgarno approach for finding a solution to the OEP equation is described herein, and a detailed illustrative example is presented for the special case of a spherically symmetric exchange-correlation potential. For the case of spherical symmetry, the relevant Dalgarno function is derived by direct integration of the appropriate radial equation while utilizing a user friendly method which explicitly treats the singular behavior at the origin and at the nodal singularities arising from the zeros of the occupied states. The derived Dalgarno function is shown to be an explicit integral functional of the exact OEP Vxcσ, thus allowing for the reduction of the OEP equation to a self-consistent integral equation for the exact exchange-correlation potential; the exact solution to this integral equation can be determined by iteration with the natural zeroth order correction given by the KLI exchange-correlation potential. Explicit analytic results are provided to illustrate the first order iterative correction beyond the KLI approximation. The derived correction term to the KLI potential explicitly involves spatially weighted products of occupied orbital densities in any assumed orbital-dependent exchange-correlation energy functional; as well, the correction term is obtained with no adjustable parameters. Moreover, if the equation for the exact optimized effective potential is further iterated, one can obtain the OEP as accurately as desired.

Estimating conformational landscapes from Cryo-EM particles by 3D Zernike polynomials.

The new developments in Cryo-EM Single Particle Analysis are helping us to understand how the macromolecular structure and function meet to drive biological processes. By capturing many states at the particle level, it is possible to address how macromolecules explore different conformations, information that is classically extracted through 3D classification. However, the limitations of classical approaches prevent us from fully understanding the complete conformational landscape due to the reduced number of discrete states accurately reconstructed. To characterize the whole structural spectrum of a macromolecule, we propose an extension of our Zernike3D approach, able to extract per-image continuous flexibility information directly from a particle dataset. Also, our method can be seamlessly applied to images, maps or atomic models, opening integrative possibilities. Furthermore, we introduce the ZART reconstruction algorithm, which considers the Zernike3D deformation fields to revert particle conformational changes during the reconstruction process, thus minimizing the blurring induced by molecular motions.

Scipion Flexibility Hub: an integrative framework for advanced analysis of conformational heterogeneity in cryoEM.

Understanding how structure and function meet to drive biological processes is progressively shifting the cryoEM field towards a more advanced analysis of macromolecular flexibility. Thanks to techniques such as single-particle analysis and electron tomography, it is possible to image a macromolecule in different states, information that can subsequently be extracted through advanced image-processing methods to build a richer approximation of a conformational landscape. However, the interoperability of all of these algorithms remains a challenging task that is left to users, preventing them from defining a single flexible workflow in which conformational information can be addressed by different algorithms. Therefore, in this work, a new framework integrated into Scipion is proposed called the Flexibility Hub. This framework automatically handles intercommunication between different heterogeneity software, simplifying the task of combining the software into workflows in which the quality and the amount of information extracted from flexibility analysis is maximized.

LDLR gene's promoter region hypermethylation in patients with familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in the LDLR, APOB, and PCSK9 genes were not found in 20-40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis of APOB and PCSK9 was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. As the LDLR gene has two CpG islands, we analyzed each island separately. The analysis of LDLR-island1 showed PR = 0.982 (CI 0.33-2.95; χ2 = 0.001; p = 0.973), also suggesting no relationship between methylation and the FH phenotype. Analysis of LDLR-island2 showed a PR of 4.12 (CI 1.43-11.88; χ2 = 13,921; p = 0.00019), indicating a possible association between methylation on this island and the FH phenotype.

CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients.

AIMS: The CYBA C242T polymorphism has been associated with cardiovascular phenotypes such as hypertension and atherosclerosis, but available data are conflicting. This report investigated the impact of this variant on hypertension and metabolic determinants of cardiovascular risk in a large Brazilian sample. METHODS: We cross-sectionally evaluated 1856 subjects (826 normotensive subjects and 1030 hypertensive patients) by clinical history, anthropometry, laboratory analysis and genotyping of the CYBA C242T polymorphism. RESULTS: Genotype frequencies in the whole population were consistent with the Hardy-Weinberg equilibrium and genotype distributions were not different between hypertensive and normotensive subjects. Hypertensive patients with the CC genotype presented lower fasting plasma glucose levels (5.9 ± 0.1 vs. 6.2 ± 0.1 mmol/l, P = 0.020) and waist circumference (94.5 ± 0.6 vs. 96.3 ± 0.6 cm, P = 0.028) than CT + TT ones. Similarly, the prevalence of diabetes mellitus and obesity was also lower in hypertensive patients carrying the CC genotype (16% vs. 21%, P = 0.041; 36% vs. 43%, P = 0.029, respectively). In addition, multiple and logistic regression analysis demonstrated that the CYBA C242T polymorphism was associated with glucose levels, waist circumference, obesity and diabetes mellitus in hypertensive patients independently of potential confounders. Conversely, in normotensive subjects, no significant difference in studied variables was detected between the genotype groups. CONCLUSIONS: These data suggest that the T allele of the CYBA C242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension.